Integrative Therapeutics, Indolplex With BR-DIM 60 Tablets
Promotes healthy cell development.
Features a patented form of DIM that is 10 times more potent than its precursor, indol-3 carbinol (I3C)
Enhanced absorption and bioavailability
Also available in tablets
This product contains no sugar, salt, yeast, wheat, gluten, dairy products, artificial flavoring, preservatives, ingredients of animal origin
Indolplex® with BR-DIM® is a dietary supplement containing diindolylmethane (DIM®) to support healthy estrogen metabolism.* Research shows DIM promotes healthy estrogen metabolism by increasing the production of 2-hydroxy estrone estrogen metabolites over the undesirable 16-hydroxy estrone estrogen metabolites.*
Provides diindolylmethane (DIM) to support healthy estrogen metabolism.*
Indolplex® with BR-DIM® is a dietary supplement that contains a patented, bioavailable form of diindolylmethane (DIM®), a dietary indole naturally present in cruciferous vegetables. Research shows DIM promotes healthy estrogen metabolism by increasing the production of 2-hydroxy estrone estrogen metabolites over the undesirable 16-hydroxy estrone estrogen metabolites.* These critical metabolites have been shown to promote healthy cell development.*
Serving Size: 2 Tablets
Servings per Container: 30
Quantity per Container: 60 Tablets
Amount Per Serving:
|Ingredient||Amount||% Daily Value|
|Calcium (as calcium carbonate)||680 mg||68%|
modified food starch, 25% diindolylmethane (DIM®), Tocophersolan, phosphatidylcholine, and silicon dioxide
† Based on 2000 calorie diet
** Daily Value (DV) not established
Directions and/or Dosage:
Take 2 tablets daily with food, or as recommended by your healthcare professional. If less support is needed, take 1 tablet daily with food.
Cellulose, modified cellulose, modified cellulose gum, silicon dioxide, stearic acid, magnesium stearate, titanium dioxide color, soy lecithin, vegetable glycerin, and carnauba wax.
Does Not Contain:
Ingredients of animal origin
Do not use if pregnant or nursing. If taking prescription drugs, consult your healthcare professional prior to use. Harmless changes in urine color may occur with the use of this product.
Indolplex and DIM are registered trademarks of and are licensed from BioResponse, L.L.C.; U.S. Patent 6,086,915.
Research on DIM:
Wattenberg, L. W., and Loub, W. D. Inhibition of polycyclic aromatic hydrocarbon-induced neoplasia by naturally occurring indoles. Cancer Res. 1978;38(5):1410-1413.
Wattenberg, L. W., Loub, W. D., Lam, L. K., and Speier, J. L. Dietary constituents altering the responses to chemical carcinogens. Fed.Proc. 5-1-1976;35(6):1327-1331.
Chen I, McDougal A, Wang F, Safe S. Aryl hydrocarbon receptor-mediated antiestrogenic and antitumorigenic activity of diindolylmethane. Carcinogenesis 1998 Sep;19:1631-9.
Wihlen, B., Ahmed, S., Inzunza, J., and Matthews, J. Estrogen receptor subtype- and promoter-specific modulation of aryl hydrocarbon receptor-dependent transcription. Mol.Cancer Res. 2009;7(6):977-986.
Williams, D. E., Katchamar, S., Larsen-Su, S. A., Stresser, D. M., Dehal, S. S., and Kupfer, D. Concurrent flavin-containing monooxygenase down regulation and cytochrome P450 induction by dietary indoles in the rat: implication for drug-drug interactions. Adv.Exp.Med.Biol. 2001;500:635-638.
Wortelboer, H. M., de Kruif, C. A., van Iersel, A. A., Falke, H. E., Noordhoek, J., and Blaauboer, B. J. Acid reaction products of indole-3-carbinol and their effects on cytochrome P450 and phase II enzymes in rat and monkey hepatocytes. Biochem.Pharmacol. 4-1-1992;43(7):1439-1447.
Wortelboer, H. M., van der Linden, E. C., de Kruif, C. A., Noordhoek, J., Blaauboer, B. J., van Bladeren, P. J., and Falke, H. E. Effects of indole-3-carbinol on biotransformation enzymes in the rat: in vivo changes in liver and small intestinal mucosa in comparison with primary hepatocyte cultures. Food Chem.Toxicol. 1992;30(7):589-599. Ý_
Xue, L., Pestka, J. J., Li, M., Firestone, G. L., and Bjeldanes, L. F. 3,3'-Diindolylmethane stimulates murine immune function in vitro and in vivo. J.Nutr.Biochem. 2008;19(5):336-344.
Yin, H., Chu, A., Li, W., Wang, B., Shelton, F., Otero, F., Nguyen, D. G., Caldwell, J. S., and Chen, Y. A. Lipid G protein-coupled receptor ligand identification using beta-arrestin PathHunter assay. J.Biol.Chem. 5-1-2009;284(18):12328-12338.
Xue, L., Firestone, G. L., and Bjeldanes, L. F. DIM stimulates IFNgamma gene expression in human breast cancer cells via the specific activation of JNK and p38 pathways. Oncogene 3-31-2005;24(14):2343-2353.
Zhang, S., Shen, H. M., and Ong, C. N. Down-regulation of c-FLIP contributes to the sensitization effect of 3,3'-diindolylmethane on TRAIL-induced apoptosis in cancer cells. Mol.Cancer Ther. 2005;4(12):1972-1981.
Zhang, X. and Malejka-Giganti, D. Effects of treatment of rats with indole-3-carbinol on apoptosis in the mammary gland and mammary adenocarcinomas. Anticancer Res. 2003;23(3B):2473-2479.
Zhao, Y. Y., Zhou, L., Pan, Y. Z., Zhao, L. J., Liu, Y. N., Yu, H., Li, Y., and Zhao, X. J. [3,3-diindolylmethane enhances the inhibitory effect of idarubicin on the growth of human prostate cancer cells]. Zhonghua Yi.Xue.Za Zhi. 3-11-2008;88(10):661-664.
Aggarwal, B. B. and Ichikawa, H. Molecular targets and anticancer potential of indole-3-carbinol and its derivatives. Cell Cycle 2005;4(9):1201-1215.
Balk JL. Indole-3-carbinol for cancer prevention. Altern Med Alert 2000; 3:105-7.
Bonnesen C, Eggleston IM, Hayes JD. Dietary indoles and isothiocyanates that are generated from cruciferous vegetables can both stimulate apoptosis and confer protection against DNA damage in human colon cell lines. Cancer Res 2001;61:6120-30.
Bradlow HL, Sepkovic DW, Telang NT, Osborne MP. Multifunctional aspects of the action of indole-3-carbinol as an antitumor agent. Ann N Y Acad Sci 1999;889:204-13.
Chen I, Safe S, Bjeldanes L. Indole-3-carbinol and diindolylmethane as aryl hydrocarbon (Ah) receptor agonists and antagonists in T47D human breast cancer cells. Biochem Pharmacol 1996;51:1069-76.
Dalessandri, K. M., Firestone, G. L., Fitch, M. D., Bradlow, H. L., and Bjeldanes, L. F. Pilot study: effect of 3,3'-diindolylmethane supplements on urinary hormone metabolites in postmenopausal women with a history of early-stage breast cancer. Nutr Cancer 2004;50(2):161-167.
Firestone, G. L. and Bjeldanes, L. F. Indole-3-carbinol and 3-3'-diindolylmethane antiproliferative signaling pathways control cell-cycle gene transcription in human breast cancer cells by regulating promoter-Sp1 transcription factor interactions. J Nutr 2003;133(7 Suppl):2448S-2455S.
Ge X, Yanni S, Rennert G, et al. 3'3-diindolylmethane induces apoptosis in human cancer cells. Biochem Biophys Res Commun 1996;228:153-8.
Lake BG, Tredger JM, Renwick AB, et al. 3'3-diindolylmethane induces CYP1A2 in cultured precision-cut human liver slices. Xenobiotica 1998;28:803-11.
McDougal A, Gupta MS, Ramamoorthy K, et al. Inhibition of carcinogen-induced rat mammary tumor growth and other estrogen-dependent responses by symmetrical dihalo-substituted analogs of diindolylmethane. Cancer Lett 2000;151:169-79.
Natl Inst Health, Natl Inst Environmental Health Sci. Indole-3-carbinol. Available at:http://ntp-server.niehs.nih.gov.
Park EJ, Pezzuto JM. Botanicals in cancer chemoprevention. Cancer Metastasis Rev 2002;21:231-55.
Riby JE, Chang GHF, Firestone GL, Bjeldanes LF. Ligand-independent activation of estrogen receptor function by 3,3'-diindolylmethane in human breast cancer cells. Biochem Pharmacol 2000;60:167-77.
Abdelrahim, M., Newman, K., Vanderlaag, K., Samudio, I., and Safe, S. 3,3'-diindolylmethane (DIM) and its derivatives induce apoptosis in pancreatic cancer cells through endoplasmic reticulum stress-dependent upregulation of DR5. Carcinogenesis 2006;27(4):717-728.
Acharya, A., Das, I., Singh, S., and Saha, T. Chemopreventive properties of indole-3-carbinol, diindolylmethane, and other constituents of cardamom against carcinogenesis. Recent Pat Food Nutr.Agric. 2010;2(2):166-177.
Ahmad, A., Kong, D., Sarkar, S. H., Wang, Z., Banerjee, S., and Sarkar, F. H. Inactivation of uPA and its receptor uPAR by 3,3'-diindolylmethane (DIM) leads to the inhibition of prostate cancer cell growth and migration. J.Cell Biochem. 6-1-2009;107(3):516-527.
Ahmad, A., Kong, D., Wang, Z., Sarkar, S. H., Banerjee, S., and Sarkar, F. H. Down-regulation of uPA and uPAR by 3,3'-diindolylmethane contributes to the inhibition of cell growth and migration of breast cancer cells. J.Cell Biochem. 11-1-2009;108(4):916-925.
Ahmad, A., Sakr, W. A., and Rahman, K. M. Anticancer properties of indole compounds: mechanism of apoptosis induction and role in chemotherapy. Curr.Drug Targets. 2010;11(6):652-666.
Albert-Puleo, M. Physiological effects of cabbage with reference to its potential as a dietary cancer-inhibitor and its use in ancient medicine. J.Ethnopharmacol. 1983;9(2-3):261-272.
Ali, S., Banerjee, S., Ahmad, A., El-Rayes, B. F., Philip, P. A., and Sarkar, F. H. Apoptosis-inducing effect of erlotinib is potentiated by 3,3'-diindolylmethane in vitro and in vivo using an orthotopic model of pancreatic cancer. Mol.Cancer Ther. 2008;7(6):1708-1719.
Ali, S., Banerjee, S., Schaffert, J. M., El-Rayes, B. F., Philip, P. A., and Sarkar, F. H. Concurrent inhibition of NF-kappaB, cyclooxygenase-2, and epidermal growth factor receptor leads to greater anti-tumor activity in pancreatic cancer. J.Cell Biochem. 2010;110(1):171-181.
Ali, S., Varghese, L., Pereira, L., Tulunay-Ugur, O. E., Kucuk, O., Carey, T. E., Wolf, G. T., and Sarkar, F. H. Sensitization of squamous cell carcinoma to cisplatin induced killing by natural agents. Cancer Lett. 6-18-2009;278(2):201-209.
Arnao, M. B., Sanchez-Bravo, J., and Acosta, M. Indole-3-carbinol as a scavenger of free radicals. Biochem.Mol. Biol.Int. 1996;39(6):1125-1134.
Auborn, K. J., Fan, S., Rosen, E. M., Goodwin, L., Chandraskaren, A., Williams, D. E., Chen, D., and Carter, T. H. Indole-3-carbinol is a negative regulator of estrogen. J.Nutr. 2003;133(7 Suppl):2470S-2475S.
Azmi, A. S., Ahmad, A., Banerjee, S., Rangnekar, V. M., Mohammad, R. M., and Sarkar, F. H. Chemoprevention of pancreatic cancer: characterization of Par-4 and its modulation by 3,3' diindolylmethane (DIM). Pharm.Res. 2008;25(9):2117-2124.
Benabadji, S. H., Wen, R., Zheng, J. B., Dong, X. C., and Yuan, S. G. Anticarcinogenic and antioxidant activity of diindolylmethane derivatives. Acta Pharmacol.Sin. 2004;25(5):666-671.
Bhatnagar, N., Li, X., Chen, Y., Zhou, X., Garrett, S. H., and Guo, B. 3,3'-diindolylmethane enhances the efficacy of butyrate in colon cancer prevention through down-regulation of survivin. Cancer Prev.Res.(Phila) 2009;2(6):581-589.
Bhuiyan, M. M., Li, Y., Banerjee, S., Ahmed, F., Wang, Z., Ali, S., and Sarkar, F. H. Down-regulation of androgen receptor by 3,3'-diindolylmethane contributes to inhibition of cell proliferation and induction of apoptosis in both hormone-sensitive LNCaP and insensitive C4-2B prostate cancer cells. Cancer Res. 10-15-2006;66(20):10064-10072.
Bovee, T. F., Schoonen, W. G., Hamers, A. R., Bento, M. J., and Peijnenburg, A. A. Screening of synthetic and plant-derived compounds for (anti)estrogenic and (anti)androgenic activities. Anal.Bioanal.Chem. 2008;390(4):1111-1119.
Bradfield, C. A. and Bjeldanes, L. F. Structure-activity relationships of dietary indoles: a proposed mechanism of action as modifiers of xenobiotic metabolism. J.Toxicol.Environ.Health 1987;21(3):311-323.
Bradlow, H. L. and Zeligs, M. A. Diindolylmethane (DIM) spontaneously form from indole-3-carbinol (I3C) during cell culture experiments. In Vivo 2010;24(4):387-391.
Carter, T. H., Liu, K., Ralph, W., Jr., Chen, D., Qi, M., Fan, S., Yuan, F., Rosen, E. M., and Auborn, K. J. Diindolylmethane alters gene expression in human keratinocytes in vitro. J.Nutr. 2002;132(11):3314-3324.
Chang, X., Firestone, G. L., and Bjeldanes, L. F. Inhibition of growth factor-induced Ras signaling in vascular endothelial cells and angiogenesis by 3,3'-diindolylmethane. Carcinogenesis 2006;27(3):541-550.
Chang, X., Tou, J. C., Hong, C., Kim, H. A., Riby, J. E., Firestone, G. L., and Bjeldanes, L. F. 3,3'-Diindolylmethane inhibits angiogenesis and the growth of transplantable human breast carcinoma in athymic mice. Carcinogenesis 2005;26(4):771-778.
Chang, Y. C., Riby, J., Chang, G. H., Peng, B. C., Firestone, G., and Bjeldanes, L. F. Cytostatic and antiestrogenic effects of 2-(indol-3-ylmethyl)-3,3'-diindolylmethane, a major in vivo product of dietary indole-3-carbinol. Biochem.Pharmacol. 9-1-1999;58(5):825-834.
Chen, D. Z., Qi, M., Auborn, K. J., and Carter, T. H. Indole-3-carbinol and diindolylmethane induce apoptosis of human cervical cancer cells and in murine HPV16-transgenic preneoplastic cervical epithelium. J.Nutr. 2001;131(12):3294-3302.
Chen, I., Hsieh, T., Thomas, T., and Safe, S. Identification of estrogen-induced genes downregulated by AhR agonists in MCF-7 breast cancer cells using suppression subtractive hybridization. Gene 1-10-2001;262(1-2):207-214.
Chen, Y., Xu, J., Jhala, N., Pawar, P., Zhu, Z. B., Ma, L., Byon, C. H., and McDonald, J. M. Fas-mediated apoptosis in cholangiocarcinoma cells is enhanced by 3,3'-diindolylmethane through inhibition of AKT signaling and FLICE-like inhibitory protein. Am.J.Pathol. 2006;169(5):1833-1842.
Chinnakannu, K., Chen, D., Li, Y., Wang, Z., Dou, Q. P., Reddy, G. P., and Sarkar, F. H. Cell cycle-dependent effects of 3,3'-diindolylmethane on proliferation and apoptosis of prostate cancer cells. J.Cell Physiol 2009;219(1):94-99.
Chintharlapalli, S., Papineni, S., and Safe, S. 1,1-bis(3'-indolyl)-1-(p-substituted phenyl)methanes inhibit growth, induce apoptosis, and decrease the androgen receptor in LNCaP prostate cancer cells through peroxisome proliferator-activated receptor gamma-independent pathways. Mol.Pharmacol. 2007;71(2):558-569.
Chintharlapalli, S., Smith, R., III, Samudio, I., Zhang, W., and Safe, S. 1,1-Bis(3'-indolyl)-1-(p-substituted phenyl)methanes induce peroxisome proliferator-activated receptor gamma-mediated growth inhibition, transactivation, and differentiation markers in colon cancer cells. Cancer Res. 9-1-2004;64(17):5994-6001.
Cho, H. J., Seon, M. R., Lee, Y. M., Kim, J., Kim, J. K., Kim, S. G., and Park, J. H. 3,3'-Diindolylmethane suppresses the inflammatory response to lipopolysaccharide in murine macrophages. J.Nutr. 2008;138(1):17-23.
Cho, S. D., Lee, S. O., Chintharlapalli, S., Abdelrahim, M., Khan, S., Yoon, K., Kamat, A. M., and Safe, S. Activation of nerve growth factor-induced B alpha by methylene-substituted diindolylmethanes in bladder cancer cells induces apoptosis and inhibits tumor growth. Mol.Pharmacol. 2010;77(3):396-404.
Cho, S. D., Lei, P., Abdelrahim, M., Yoon, K., Liu, S., Guo, J., Papineni, S., Chintharlapalli, S., and Safe, S. 1,1-bis(3'-indolyl)-1-(p-methoxyphenyl)methane activates Nur77-independent proapoptotic responses in colon cancer cells. Mol.Carcinog. 2008;47(4):252-263.
Choi, K. H., Kim, H. K., Kim, J. H., Choi, E. S., Shin, J. A., Lee, S. O., Chintharlapalli, S., Safe, S., Abdelrahim, M., Kong, G., Choi, H. S., Jung, J. Y., Cho, H. T., Cho, N. P., and Cho, S. D. The p38 MAPK pathway is critical for 5,5'-dibromodiindolylmethane-induced apoptosis to prevent oral squamous carcinoma cells. Eur.J.Cancer Prev. 2010;19(2):153-159.
Contractor, R., Samudio, I. J., Estrov, Z., Harris, D., McCubrey, J. A., Safe, S. H., Andreeff, M., and Konopleva, M. A novel ring-substituted diindolylmethane,1,1-bis[3'-(5-methoxyindolyl)]-1-(p-t-butylphenyl) methane, inhibits extracellular signal-regulated kinase activation and induces apoptosis in acute myelogenous leukemia. Cancer Res. 4-1-2005;65(7):2890-2898.
Dashwood, R. H., Fong, A. T., Arbogast, D. N., Bjeldanes, L. F., Hendricks, J. D., and Bailey, G. S. Anticarcinogenic activity of indole-3-carbinol acid products: ultrasensitive bioassay by trout embryo microinjection. Cancer Res. 7-1-1994;54(13):3617-3619.
de Kruif, C. A., Marsman, J. W., Venekamp, J. C., Falke, H. E., Noordhoek, J., Blaauboer, B. J., and Wortelboer, H. M. Structure elucidation of acid reaction products of indole-3-carbinol: detection in vivo and enzyme induction in vitro. Chem.Biol.Interact. 1991;80(3):303-315.
Degner, S. C., Papoutsis, A. J., Selmin, O., and Romagnolo, D. F. Targeting of aryl hydrocarbon receptor-mediated activation of cyclooxygenase-2 expression by the indole-3-carbinol metabolite 3,3'-diindolylmethane in breast cancer cells. J.Nutr. 2009;139(1):26-32.
Del Priore G., Gudipudi, D. K., Montemarano, N., Restivo, A. M., Malanowska-Stega, J., and Arslan, A. A. Oral diindolylmethane (DIM): pilot evaluation of a nonsurgical treatment for cervical dysplasia. Gynecol.Oncol. 2010;116(3):464-467.
Dong, L., Xia, S., Gao, F., Zhang, D., Chen, J., and Zhang, J. 3,3'-Diindolylmethane attenuates experimental arthritis and osteoclastogenesis. Biochem.Pharmacol. 3-1-2010;79(5):715-721.
Fan, S., Meng, Q., Saha, T., Sarkar, F. H., and Rosen, E. M. Low concentrations of diindolylmethane, a metabolite of indole-3-carbinol, protect against oxidative stress in a BRCA1-dependent manner. Cancer Res. 8-1-2009;69(15):6083-6091.
Fares, F., Azzam, N., Appel, B., Fares, B., and Stein, A. The potential efficacy of 3,3'-diindolylmethane in prevention of prostate cancer development. Eur.J.Cancer Prev. 2010;19(3):199-203.
Firestone, G. L., and Sundar, S. N. Minireview: modulation of hormone receptor signaling by dietary anticancer indoles. Mol.Endocrinol. 2009;23(12):1940-1947.
Gallagher, E. P. Using salmonid microarrays to understand the dietary modulation of carcinogenesis in rainbow trout. Toxicol.Sci. 2006;90(1):1-4.
Gamet-Payrastre, L., Lumeau, S., Gasc, N., Cassar, G., Rollin, P., and Tulliez, J. Selective cytostatic and cytotoxic effects of glucosinolates hydrolysis products on human colon cancer cells in vitro. Anticancer Drugs 1998;9(2):141-148.
Garikapaty, V. P., Ashok, B. T., Tadi, K., Mittelman, A., and Tiwari, R. K. 3,3'-Diindolylmethane downregulates pro-survival pathway in hormone-independent prostate cancer. Biochem.Biophys.Res.Commun. 2-10-2006;340(2):718-725.
Garikapaty, V. P., Ashok, B. T., Tadi, K., Mittelman, A., and Tiwari, R. K. Synthetic dimer of indole-3-carbinol: second generation diet-derived anti-cancer agent in hormone sensitive prostate cancer. Prostate 4-1-2006;66(5):453-462.
Ge, X., Fares, F. A., and Yannai, S. Induction of apoptosis in MCF-7 cells by indole-3-carbinol is independent of p53 and Bax. Anticancer Res. 1999;19(4B):3199-3203.
Gong, Y., Firestone, G. L., and Bjeldanes, L. F. 3,3'-diindolylmethane is a novel topoisomerase IIalpha catalytic inhibitor that induces S-phase retardation and mitotic delay in human hepatoma HepG2 cells. Mol.Pharmacol. 2006;69(4):1320-1327.
Gong, Y., Sohn, H., Xue, L., Firestone, G. L., and Bjeldanes, L. F. 3,3'-Diindolylmethane is a novel mitochondrial H(+)-ATP synthase inhibitor that can induce p21(Cip1/Waf1) expression by induction of oxidative stress in human breast cancer cells. Cancer Res. 5-1-2006;66(9):4880-4887.
Gross-Steinmeyer, K., Stapleton, P. L., Liu, F., Tracy, J. H., Bammler, T. K., Quigley, S. D., Farin, F. M., Buhler, D. R., Safe, S. H., Strom, S. C., and Eaton, D. L. Phytochemical-induced changes in gene expression of carcinogen-metabolizing enzymes in cultured human primary hepatocytes. Xenobiotica 2004;34(7):619-632.
Gross-Steinmeyer, K., Stapleton, P. L., Tracy, J. H., Bammler, T. K., Strom, S. C., Buhler, D. R., and Eaton, D. L. Modulation of aflatoxin B1-mediated genotoxicity in primary cultures of human hepatocytes by diindolylmethane, curcumin, and xanthohumols. Toxicol Sci. 2009;112(2):303-310.
Gullett, N. P., Ruhul Amin, A. R., Bayraktar, S., Pezzuto, J. M., Shin, D. M., Khuri, F. R., Aggarwal, B. B., Surh, Y. J., and Kucuk, O. Cancer prevention with natural compounds. Semin.Oncol. 2010;37(3):258-281.
Heath, E. I., Heilbrun, L. K., Li, J., Vaishampayan, U., Harper, F., Pemberton, P., and Sarkar, F. H. A phase I dose-escalation study of oral BR-DIM (BioResponse 3,3'- Diindolylmethane) in castrate-resistant, non-metastatic prostate cancer. Am.J.Transl.Res. 2010;2(4):402-411.
Hestermann, E. V. and Brown, M. Agonist and chemopreventative ligands induce differential transcriptional cofactor recruitment by aryl hydrocarbon receptor. Mol.Cell Biol. 2003;23(21):7920-7925.
Hong, C., Firestone, G. L., and Bjeldanes, L. F. Bcl-2 family-mediated apoptotic effects of 3,3'-diindolylmethane (DIM) in human breast cancer cells. Biochem.Pharmacol. 3-15-2002;63(6):1085-1097.
Hong, C., Kim, H. A., Firestone, G. L., and Bjeldanes, L. F. 3,3'-Diindolylmethane (DIM) induces a G(1) cell cycle arrest in human breast cancer cells that is accompanied by Sp1-mediated activation of p21(WAF1/CIP1) expression. Carcinogenesis 2002;23(8):1297-1305.
Hong, J., Samudio, I., Liu, S., Abdelrahim, M., and Safe, S. Peroxisome proliferator-activated receptor gamma-dependent activation of p21 in Panc-28 pancreatic cancer cells involves Sp1 and Sp4 proteins. Endocrinology 2004;145(12):5774-5785.
Hsu, E. L., Chen, N., Westbrook, A., Wang, F., Zhang, R., Taylor, R. T., and Hankinson, O. CXCR4 and CXCL12 down-regulation: a novel mechanism for the chemoprotection of 3,3'-diindolylmethane for breast and ovarian cancers. Cancer Lett. 6-28-2008;265(1):113-123.
Hsu, E. L., Chen, N., Westbrook, A., Wang, F., Zhang, R., Taylor, R. T., and Hankinson, O. Modulation of CXCR4, CXCL12, and Tumor Cell Invasion Potential In Vitro by Phytochemicals. J.Oncol. 2009;2009:491985.
Hsu, J. C., Zhang, J., Dev, A., Wing, A., Bjeldanes, L. F., and Firestone, G. L. Indole-3-carbinol inhibition of androgen receptor expression and downregulation of androgen responsiveness in human prostate cancer cells. Carcinogenesis 2005;26(11):1896-1904.
Huang, J., Plass, C., and Gerhauser, C. Cancer chemoprevention by targeting the epigenome. Curr Drug Targets. 2011;12(13):1925-1956.
Huang, Z., Zuo, L., Zhang, Z., Liu, J., Chen, J., Dong, L., and Zhang, J. 3,3'-Diindolylmethane decreases VCAM-1 expression and alleviates experimental colitis via a BRCA1-dependent antioxidant pathway. Free Radic.Biol.Med. 1-15-2011;50(2):228-236.
Ichite, N., Chougule, M. B., Jackson, T., Fulzele, S. V., Safe, S., and Singh, M. Enhancement of docetaxel anticancer activity by a novel diindolylmethane compound in human non-small cell lung cancer. Clin.Cancer Res. 1-15-2009;15(2):543-552.
Ichite, N., Chougule, M., Patel, A. R., Jackson, T., Safe, S., and Singh, M. Inhalation delivery of a novel diindolylmethane derivative for the treatment of lung cancer. Mol.Cancer Ther. 2010;9(11):3003-3014.
Jellinck, P. H., Forkert, P. G., Riddick, D. S., Okey, A. B., Michnovicz, J. J., and Bradlow, H. L. Ah receptor binding properties of indole carbinols and induction of hepatic estradiol hydroxylation. Biochem.Pharmacol. 3-9-1993;45(5):1129-1136.
Jellinck, P. H., Makin, H. L., Sepkovic, D. W., and Bradlow, H. L. Influence of indole carbinols and growth hormone on the metabolism of 4-androstenedione by rat liver microsomes. J.Steroid Biochem.Mol. Biol. 1993;46(6):791-798.
Jin, Y., Zou, X., and Feng, X. 3,3'-Diindolylmethane negatively regulates Cdc25A and induces a G2/M arrest by modulation of microRNA 21 in human breast cancer cells. Anticancer Drugs 2010;21(9):814-822.
Kandala, P. K. and Srivastava, S. K. Activation of checkpoint kinase 2 by 3,3'-diindolylmethane is required for causing G2/M cell cycle arrest in human ovarian cancer cells. Mol.Pharmacol. 2010;78(2):297-309.
Kassie, F., Anderson, L. B., Scherber, R., Yu, N., Lahti, D., Upadhyaya, P., and Hecht, S. S. Indole-3-carbinol inhibits 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone plus benzo(a)pyrene-induced lung tumorigenesis in A/J mice and modulates carcinogen-induced alterations in protein levels. Cancer Res. 7-1-2007;67(13):6502-6511.
Kassie, F., Melkamu, T., Endalew, A., Upadhyaya, P., Luo, X., and Hecht, S. S. Inhibition of lung carcinogenesis and critical cancer-related signaling pathways by N-acetyl-S-(N-2-phenethylthiocarbamoyl)-l-cysteine, indole-3-carbinol and Myo-inositol, alone and in combination. Carcinogenesis 2010;31(9):1634-1641.
Katchamart, S., Stresser, D. M., Dehal, S. S., Kupfer, D., and Williams, D. E. Concurrent flavin-containing monooxygenase down-regulation and cytochrome P-450 induction by dietary indoles in the rat: implications for drug-drug interaction. Drug Metab Dispos. 2000;28(8):930-936.
Khwaja, F. S., Wynne, S., Posey, I., and Djakiew, D. 3,3'-diindolylmethane induction of p75NTR-dependent cell death via the p38 mitogen-activated protein kinase pathway in prostate cancer cells. Cancer Prev.Res.(Phila) 2009;2(6):566-571.
Kim, E. J., Park, H., Kim, J., and Park, J. H. 3,3'-diindolylmethane suppresses 12-O-tetradecanoylphorbol-13-acetate-induced inflammation and tumor promotion in mouse skin via the downregulation of inflammatory mediators. Mol.Carcinog. 2010;49(7):672-683.
Kim, E. J., Park, S. Y., Shin, H. K., Kwon, D. Y., Surh, Y. J., and Park, J. H. Activation of caspase-8 contributes to 3,3'-Diindolylmethane-induced apoptosis in colon cancer cells. J.Nutr. 2007;137(1):31-36.
Kim, E. J., Shin, M., Park, H., Hong, J. E., Shin, H. K., Kim, J., Kwon, D. Y., and Park, J. H. Oral administration of 3,3'-diindolylmethane inhibits lung metastasis of 4T1 murine mammary carcinoma cells in BALB/c mice. J.Nutr. 2009;139(12):2373-2379.
Kim, Y. H., Kwon, H. S., Kim, D. H., Shin, E. K., Kang, Y. H., Park, J. H., Shin, H. K., and Kim, J. K. 3,3'-diindolylmethane attenuates colonic inflammation and tumorigenesis in mice. Inflamm.Bowel.Dis. 2009;15(8):1164-1173.
Kim, Y. S., and Milner, J. A. Targets for indole-3-carbinol in cancer prevention. J.Nutr.Biochem. 2005;16(2):65-73.
Kong, D., Banerjee, S., Huang, W., Li, Y., Wang, Z., Kim, H. R., and Sarkar, F. H. Mammalian target of rapamycin repression by 3,3'-diindolylmethane inhibits invasion and angiogenesis in platelet-derived growth factor-D-overexpressing PC3 cells. Cancer Res. 3-15-2008;68(6):1927-1934.
Kong, D., Li, Y., Wang, Z., Banerjee, S., and Sarkar, F. H. Inhibition of angiogenesis and invasion by 3,3'-diindolylmethane is mediated by the nuclear factor-kappaB downstream target genes MMP-9 and uPA that regulated bioavailability of vascular endothelial growth factor in prostate cancer. Cancer Res. 4-1-2007;67(7):3310-3319.
Kunimasa, K., Kobayashi, T., Kaji, K., and Ohta, T. Antiangiogenic effects of indole-3-carbinol and 3,3'-diindolylmethane are associated with their differential regulation of ERK1/2 and Akt in tube-forming HUVEC. J.Nutr. 2010;140(1):1-6.
Le, H. T., Schaldach, C. M., Firestone, G. L., and Bjeldanes, L. F. Plant-derived 3,3'-Diindolylmethane is a strong androgen antagonist in human prostate cancer cells. J.Biol.Chem. 6-6-2003;278(23):21136-21145.
Lee, S. H., Kim, J. S., Yamaguchi, K., Eling, T. E., and Baek, S. J. Indole-3-carbinol and 3,3'-diindolylmethane induce expression of NAG-1 in a p53-independent manner. Biochem.Biophys.Res.Commun. 3-4-2005;328(1):63-69.
Lee, S. O., Li, X., Khan, S., and Safe, S. Targeting NR4A1 (TR3) in cancer cells and tumors. Expert.Opin.Ther.Targets. 2011;15(2):195-206.
Leibelt, D. A., Hedstrom, O. R., Fischer, K. A., Pereira, C. B., and Williams, D. E. Evaluation of chronic dietary exposure to indole-3-carbinol and absorption-enhanced 3,3'-diindolylmethane in Sprague-Dawley rats. Toxicol.Sci. 2003;74(1):10-21.
Leong, H., Firestone, G. L., and Bjeldanes, L. F. Cytostatic effects of 3,3'-diindolylmethane in human endometrial cancer cells result from an estrogen receptor-mediated increase in transforming growth factor-alpha expression. Carcinogenesis 2001;22(11):1809-1817.
Leong, H., Riby, J. E., Firestone, G. L., and Bjeldanes, L. F. Potent ligand-independent estrogen receptor activation by 3,3'-diindolylmethane is mediated by cross-talk between the protein kinase A and mitogen-activated protein kinase signaling pathways. Mol.Endocrinol. 2004;18(2):291-302.
Li, Y., Kong, D., Wang, Z., and Sarkar, F. H. Regulation of microRNAs by natural agents: an emerging field in chemoprevention and chemotherapy research. Pharm.Res. 2010;27(6):1027-1041.
Li, Y., Li, X., and Guo, B. Chemopreventive agent 3,3'-diindolylmethane selectively induces proteasomal degradation of class I histone deacetylases. Cancer Res. 1-15-2010;70(2):646-654.
Li, Y., Li, X., and Sarkar, F. H. Gene expression profiles of I3C- and DIM-treated PC3 human prostate cancer cells determined by cDNA microarray analysis. J.Nutr. 2003;133(4):1011-1019.
Li, Y., VandenBoom, T. G., Kong, D., Wang, Z., Ali, S., Philip, P. A., and Sarkar, F. H. Up-regulation of miR-200 and let-7 by natural agents leads to the reversal of epithelial-to-mesenchymal transition in gemcitabine-resistant pancreatic cancer cells. Cancer Res. 8-15-2009;69(16):6704-6712.
Li, Y., VandenBoom, T. G., Wang, Z., Kong, D., Ali, S., Philip, P. A., and Sarkar, F. H. miR-146a suppresses invasion of pancreatic cancer cells. Cancer Res. 2-15-2010;70(4):1486-1495.
Li, Y., Wang, Z., Kong, D., Murthy, S., Dou, Q. P., Sheng, S., Reddy, G. P., and Sarkar, F. H. Regulation of FOXO3a/beta-catenin/GSK-3beta signaling by 3,3'-diindolylmethane contributes to inhibition of cell proliferation and induction of apoptosis in prostate cancer cells. J.Biol.Chem. 7-20-2007;282(29):21542-21550.
Liu, S., Abdelrahim, M., Khan, S., Ariazi, E., Jordan, V. C., and Safe, S. Aryl hydrocarbon receptor agonists directly activate estrogen receptor alpha in MCF-7 breast cancer cells. Biol. Chem. 2006;387(9):1209-1213.
Loub, W. D., Wattenberg, L. W., and Davis, D. W. Aryl hydrocarbon hydroxylase induction in rat tissues by naturally occurring indoles of cruciferous plants. J.Natl.Cancer Inst. 1975;54(4):985-988.
Maciejewska, D., Rasztawicka, M., Wolska, I., Anuszewska, E., and Gruber, B. Novel 3,3'-diindolylmethane derivatives: synthesis and cytotoxicity, structural characterization in the solid state. Eur.J.Med.Chem. 2009;44(10):4136-4147.
McCarty, M. F. and Block, K. I. Multifocal angiostatic therapy: an update. Integr. Cancer Ther. 2005;4(4):301-314.
McDanell, R., McLean, A. E., Hanley, A. B., Heaney, R. K., and Fenwick, G. R. Differential induction of mixed-function oxidase (MFO) activity in rat liver and intestine by diets containing processed cabbage: correlation with cabbage levels of glucosinolates and glucosinolate hydrolysis products. Food Chem.Toxicol. 1987;25(5):363-368.
McDougal, A., Gupta, M. S., Morrow, D., Ramamoorthy, K., Lee, J. E., and Safe, S. H. Methyl-substituted diindolylmethanes as inhibitors of estrogen-induced growth of T47D cells and mammary tumors in rats. Breast Cancer Res. Treat. 2001;66(2):147-157.
McGuire, K. P., Ngoubilly, N., Neavyn, M., and Lanza-Jacoby, S. 3,3'-diindolylmethane and paclitaxel act synergistically to promote apoptosis in HER2/Neu human breast cancer cells. J.Surg.Res. 5-15-2006;132(2):208-213.
Moiseeva, E. P., Almeida, G. M., Jones, G. D., and Manson, M. M. Extended treatment with physiologic concentrations of dietary phytochemicals results in altered gene expression, reduced growth, and apoptosis of cancer cells. Mol.Cancer Ther. 2007
Agape Nutrition Inventory Update
We have received unprecedented demand across a wide range of categories as the impact of coronavirus COVID-19 has continued to spread over the past several months, and as a result, have experienced several availability issues.
We are working very closely with our manufacture and supplier partners to quickly increase availability across all product categories. We are now operating normally with intermittent out of stock levels, which generally do not last long and are quickly being replenished by our brand partners.
Please Be Aware of Any Possible Shipping Delays:
(1) Slight delays with fulfillment processing may occur as manufacture and distributor warehouses are experiencing higher than normal volume and demand for nutritional items.
(2) Shipping carriers are experiencing delays. This is due to increased shipments resulting from the COVID-19 pandemic combined with any holidays, and/or natural disasters. Expedited shipping (2-Day, 3-Day, and Next-Day) are not guaranteed by the carriers and does not include weekend delivery. Please reach out to the shipping carrier for more information.
(3) Please be aware of severe weather conditions in or around your location and surrounding states that my affect the timeliness of delivery.
Orders cannot be cancelled once the order confirmation is received.
Agape Nutrition is proud to offer: United States Postal Service (USPS) and United Parcel Service (UPS) as our standard shipping carriers and their services. Shipping rates are determined in real time or carrier book rate by weight and distance. Shipping Options are determined and reflected upon check out, for your choosing. If an option below is not listed upon check out, your package may not meet the weight requirement or the service may not be available to the address location. You will receive an automated invoice of your order in your email inbox. Tracking is generally applied within 24 to 48 hours of receipt, unless otherwise notified.
We pride ourselves on providing fast service at competitive prices.
Orders received by 12:00 pm Pacific Standard Time (PST) are generally processed within 24 to 48 hours, which is dependent upon the daily order volume. Although, most orders are processed and shipped within 24 hours of receipt, this is not a guarantee. Tracking is updated within 24 to 48 hours after processing and the package has shipped.
NOTE: Shipping carriers are experiencing delays. This is due to increased shipments resulting from the COVID-19 pandemic combined with any holidays, and/or natural disasters.
NOTE: Expedited shipping (2-Day, 3-Day, and Next-Day) are not guaranteed by the carriers and does not include weekend delivery. Due to no carrier guarantees, delayed or late packages are not eligible for refunds. This is a stipulation directly from the shipping carriers and is out of our control.
The Shipping Service Guarantee Remains Suspended for Most Shipments
*Please reach out to the shipping carrier for more information.
|USPS Services (Business Days)||UPS Services (Business Days)|
|1-3 Days||USPS First-Class Mail||2 Days||UPS 2 Day Air|
|1-3 Days||USPS Priority Mail||3 Days||UPS 3 Day Select|
|2-9 Days||USPS Parcel Select||1-7 Days||UPS Ground|
Please Note: No Saturday Delivery.
FREE SHIPPING is offered to orders that meet or exceed $99, by applying the promo code: FREESHIP and click the ADD button upon check out. FREE SHIPPING is USPS Standard delivery service or UPS Standard Ground, if the first option is not available to your shipping location. Offer excludes specialty products and other discounts.
If FREE SHIPPING is not desired, simply do not apply the promo code. All available shipping options for your order will be displayed.
All discounts and promotional offers are calculated before shipping and handling rates are applied.
Orders cannot be cancelled or changed once the order has been placed and the confirmation is received.
- Products may process and ship faster then expected.
- Products may be automated to process directly after the order is confirmed.
- Product warehouses may be in different states and time zones.
- Orders may take up to 72 hours to process a cancellation or change.
Products may ship faster then expected, and many are automated to process directly after order confirmation. We work directly with top professional manufactures and distributors from across the United States, in all time zones. There are a lot of cogs and wheels turning to process and ship your order efficiently to meet an on time delivery target. When you request a cancellation or change of an order, it may take up to 72 hours to process your request. This process may involve voiding orders in computer systems, removing items from back order logs, pulling items from production schedules and sometimes stopping orders at the shipping dock or warehouse. Our order fulfillment may be performed by many quick hands, in different states and time zones. Therefore, we cannot offer or guarantee order cancellations after the order has been received.
Orders should be placed via the web with payment by MasterCard, Visa, Discover, American Express, PayPal or Amazon Pay, etc.
Agape Nutrition is proud to ship to 62 states and territories of the United States.
- All 50 United States
- Armed Forces: Americas (AA)
Orders shipped to U.S. military addresses (APO/FPO/DPO) will ship via United States Postal Service (USPS) at the carrier book rate; delivery of these orders may be delayed by one (1) business day.
Agape Nutrition does not offer international orders or shipping at this time, outside the 62 states and territories of the United States.
Heat Sensitive Orders
Products requiring shipment in a cool environment (perishable and frozen items) are subject to special shipping procedures due to their sensitive nature to ensure customers receive products in good condition. Heat sensitive items are shipped using sealed thermal bubble bag, ice pack or brick, resealable bag and extra padding to ensure a cool environment. We do not recommend heat sensitive item ship to territories of the United States, and we cannot be held responsible for cooled environment degradation to these destinations.
Agape Nutrition recommends that heat sensitive products ship with your preference of any 1-3 Day delivery service. We do not offer overnight or next day delivery service at this time. Saturday delivery is not available or guaranteed, unless offered by the shipping carrier as part of the normal delivery.
- All heat sensitive items will ship on Monday and Tuesday only. This is the ensure that heat sensitive orders are delivered before weekends.
- Heat sensitive items are not eligible for return, credit, or refund. As we cannot guarantee cool storage or efficacy of the product, after the order has been delivered.
- Delays in shipping service delivery, caused an issue? See our return policy for further information.
Drop Ship Orders
Shipping may be different from the warehouse(s) we work with, however we do our best to match the pricing and type of shipping originally selected. Please note that some manufactures add 1-2 days for their processing times before shipping your order.
Signature is required for:
- Orders of a high dollar amount.
- Biotics Research NW shipments.
- Vielight shipments.
- Richway shipments.
- All electronic devices.
- All laboratory test kits.
Drop ship orders may be utilized in the following scenarios:
- Out of stock in our dispensary.
- Allows faster shipping time.
- Special order items.
- Drop ship only item.
May be available on specific items only. Discounts will be available on the item order page, with the volume and discount clearly indicated.
We do not offer commercial entity fulfillment (wholesaler, distributor, re-seller). Orders are processed for quantities of personal consumption only. Accounts are monitored and deactivated for misuse, at Agape Nutrition's discretion.
Out of Stock Items
If an item ordered is out of stock with the manufacture or any warehouse we work with, you will automatically receive the remainder of your order.
- We may: search for another fulfillment warehouse in order to drop ship your item.
- We may: notify you if the item can be fulfilled within 1-2 weeks, so that you may choose to wait for fulfillment or cancel the order.
- We may: cancel the item or order for a full refund. You will be notified by email of any unfulfillable cancellations.
Please be aware of severe weather and hazardous conditions in your area or other states that may affect the timeliness of your package delivery. Agape Nutrition can not be responsible for severe weather and unforeseen incidents that may impact the processing times and/or shipping services. We will work to ensure the safety of our employees while minimizing effects on service. Contingency plans are in place to help ensure that shipments arrive at their final destinations as quickly as conditions permit.
All prices are subject to change without notice. Agape Nutrition is not liable for errors or omissions.