Thursday, 31 October 2013

Phytochemicals in Foods - 10 Health Benefits of Indole-3-carbinol

Indole-3-carbinol is a phytochemical in the class of Indoles, found abundantly in cabbage, kale, brussels sprouts, rutabaga, mustard greens, broccoli, etc.

Health Benefits
1. Breast cancer
In the investigation of
treatment of highly tumorigenic MDA-MB-231 human breast cancer cells with indole-3-carbinol (I3C) directly inhibited the extracellular elastase-dependent cleavage of membrane-associated CD40, showed that I3C directly inhibits the elastase-mediated proteolytic processing of CD40, which alters downstream signaling to disrupt NF-kappaB-induced cell survival and proliferative responses. Furthermore, the establish of a new I3C-mediated antiproliferative cascade has significant therapeutic potential for treatment of human cancers associated with high levels of elastase and its CD40 membrane substrate, according to "Direct inhibition of elastase activity by indole-3-carbinol triggers a CD40-TRAF regulatory cascade that disrupts NF-kappaB transcriptional activity in human breast cancer cells" by Aronchik I, Bjeldanes LF, Firestone GL.(1)

2. Lung cancer
In the examination of the inhibitory effects of N-acetyl-S-(N-2-phenethylthiocarbamoyl)-l-cysteine (PEITC-NAC), myo-inositol (MI) and indole-3-carbinol (I3C) or 3,3'-diindolylmethane (DIM), alone and in combination, on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) plus benzo[a]pyrene (BaP)-induced A/J mouse lung tumorigenesis and proliferation of A549 cells and human bronchial epithelial cells (HBECs) and relevant potential mechanisms, found that the assessment of the anti-proliferative effects of the individual agents or their combinations showed significant reductions in the proliferation of cigarette smoke condensate (CSC)-pretreated HBEC (reduction by 30-41% at 48 h and 41-58% at 72 h) and A549 cells (30-43% at 48 h and 40-59% at 72 h), but not in dimethyl sulfoxide-pretreated HBEC. Combinatorial treatment with the agents also caused marked reductions in the activation of Akt, extracellular signal-regulated kinase and nuclear factor-kappaB in lung tumor tissues, CSC-pretreated HBEC and A549 cells, according to "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" by Kassie F, Melkamu T, Endalew A, Upadhyaya P, Luo X, Hecht SS.(2)

3. Pancreatic cell lines
In the examination of the possible mechanism of I3C-enhanced efficacy on pancreatic cell lines (BxPC-3, Mia Paca-2, PL-45, AsPC-1 and PANC-1) for modulation of human equilibrative nucleoside transporter 1 (hENT1) expression, showed that Gemcitabine alone showed no effect on hENT1 expression. However, combining gemcitabine with I3C further increased hENT1 expression. Cell viability assays revealed no effect of I3C on normal cells, hTERT-HPNE. hENT1-specific inhibitor, nitrobenzylthioinosine, significantly abrogated I3C-induced gemcitabine cytotoxicity, further demonstrating its specificity, according to "Enhanced efficacy of gemcitabine by indole-3-carbinol in pancreatic cell lines: the role of human equilibrative nucleoside transporter 1" by Wang H, Word BR, Lyn-Cook BD.(3)

4. Prostate cancer
In the examination of the chemopreventive effects and the molecular mechanism of I3C, particularly the anti-oxidative stress pathway regulated by nuclear erythroid related factor 2 (Nrf2), found that treatments of transgenic adenocarcinoma of mouse prostate, TRAMP C1 cells with I3C also resulted in the induction of Nrf2-mediated genes. I3C significantly suppressed the incidence of palpable tumor and reduced the genitourinary weight in TRAMP mice. Western blots and qPCR analyses of prostate tissues showed that I3C induced the expression of Nrf2, NAD(P)H quinine oxidoreductase 1 (NQO-1) as well as cell cycle and apoptosis related biomarkers in I3C-fed TRAMP mice, according to "In vivo pharmacodynamics of indole-3-carbinol in the inhibition of prostate cancer in transgenic adenocarcinoma of mouse prostate (TRAMP) mice: Involvement of Nrf2 and cell cycle/apoptosis signaling pathways" by Wu TY, Saw CL, Khor TO, Pung D, Boyanapalli SS, Kong AN.(4)

5. Vulval intraepithelial neoplasia
In the evaluation of the effectiveness and safety of medical interventions for high grade Vulval intraepithelial neoplasia (VIN), a pre-malignant condition of the vulval skin, associated with infection with human papilloma virus (HPV) infection, indicated that four trials met our inclusion criteria: three assessed the effectiveness of topical imiquimod versus placebo in women with high grade VIN; one examined low versus high dose indole-3-carbinol in similar women. Meta-analysis of three trials found that the proportion of women who responded to treatment at 5 to 6 months was much higher in the group who received topical imiquimod than in the group who received placebo (relative risk (RR) = 11.95, 95% confidence interval (CI) 3.21 to 44.51), according to "Medical interventions for high grade vulval intraepithelial neoplasia" by Pepas L, Kaushik S, Bryant A, Nordin A, Dickinson HO.(5)

6. Estrogen Metabolism
In the investigation of determine whether a breast health supplement containing indole-3-carbinol and hydroxymatairesinol lignan would alter estrogen metabolism to favour C-2 hydroxylation and reduce C-16 hydroxylation, found that Supplementation with a mixture of indole-3-carbinol and HMR lignan in women significantly increased estrogen C-2 hydroxylation. This may constitute a mechanism for the reduction of breast cancer risk as well as risk for other estrogen-related cancers. Further studies with higher numbers of subjects are indicated, according to "Effects of A Breast-Health Herbal Formula Supplement on Estrogen Metabolism in Pre- and Post-Menopausal Women not Taking Hormonal Contraceptives or Supplements: A Randomized Controlled Trial" by Laidlaw M, Cockerline CA, Sepkovic DW.(6)

7. Oral cancer
In the investigation ofthe antitumor effects of OSU-A9, a structurally optimized I3C derivative, in a panel of oral squamous cell carcinoma cell lines, SCC4, SCC15, and SCC2095, showed that The antiproliferative effect of OSU-A9 was approximately two-orders-of-magnitude higher than that of I3C. Importantly, normal human oral keratinocytes were less sensitive to OSU-A9 than oral cancer cells. This antiproliferative effect of OSU-A9 was attributable to the induction of mitochondrial-dependent apoptosis as evidenced by sub-G1 accumulation of cells, poly ADP-ribose polymerase cleavage, and cytochrome c release from the mitochondria. OSU-A9 down regulates Akt and NF-κB signaling pathways, leading to changes in many downstream effectors involved in regulating cell cycle and apoptosis, according to "A novel indole-3-carbinol derivative inhibits the growth of human oral squamous cell carcinoma in vitro" by Weng JR, Bai LY, Omar HA, Sargeant AM, Yeh CT, Chen YY, Tsai MH, Chiu CF.(7)

8. Cancer prevention
In the review of botanical and nutritional compounds have been used for the treatment of cancer throughout history, indicated that several lead compounds, such as genistein (from soybeans), lycopene (from tomatoes), brassinin (from cruciferous vegetables), sulforaphane (from asparagus), indole-3-carbinol (from broccoli), and resveratrol (from grapes and peanuts) are in preclinical or clinical trials for cancer chemoprevention. Phytochemicals have great potential in cancer prevention because of their safety, low cost, and oral bioavailability, according to "Cancer prevention with natural compounds" by Gullett NP, Ruhul Amin AR, Bayraktar S, Pezzuto JM, Shin DM, Khuri FR, Aggarwal BB, Surh YJ, Kucuk O.(8)

9. Nasopharyngeal cancer
In the examination of the
apoptotic effects of indole-3-carbinol (I3C) in many human cancer cells, found that Treatment with I3C significantly suppressed XIAP, c-IAP1 and Survivin protein, while elevated the expression of Omi, Smac and Cyto-c. Fas/FasL and MAPK pathway were involved in the induction of apoptosis. Taken together, these results demonstrated that I3C may induce mitochondria-mediated apoptosis via the Fas death receptor in CNE-2 cells. This molecular mechanism for apoptotic effect of I3C on nasopharyngeal cancer cells suggested that I3C might become a preventive and therapeutic agent against nasopharyngeal cancer, according to "Indole-3-carbinol (I3C)-induced apoptosis in nasopharyngeal cancer cells through Fas/FasL and MAPK pathway" by Xu Y, Zhang J, Dong WG.(9)

10. Colon cancer
In an easy two-step synthesis for 4-methoxyindole-3-carbinol (4MeOI3C), the expected breakdown product of 4-methoxyglucobrassicin during ingestion. 4MeOI3C inhibited the proliferation of human colon cancer cells DLD-1 and HCT 116 with IC(50) values of 116 microM and 96 microM, respectively, found that after 48 h in vitro, and is therefore a more potent inhibitor than indole-3-carbinol (I3C). 4MeOI3C and I3C combined in different molar ratios inhibited proliferation in a nearly additive to slightly synergistic manner. Proliferation was inhibited by 100 microM 4MeOI3C after 48 h without affecting cell cycle phase distribution, indicating an overall-slowdown effect on the cell cycle, according to "Effect of 4-methoxyindole-3-carbinol on the proliferation of colon cancer cells in vitro, when treated alone or in combination with indole-3-carbinol" by Kronbak R, Duus F, Vang O.(10)

11. Etc.

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