Phytochemical Indole-3-carbinol

Indole-3-carbinol is a phytochemical in the class of Indoles, by the breaking down of the glucosinolate glucobrassicin,  found abundantly in cabbage, kale, Brussels sprouts, rutabaga, mustard greens, broccoli, etc.

1, Breast cancer
Breast cancer (malignant breast neoplasm) is a cancer started in the tissues of the breast either from the inner lining of milk ducts (Ductal carcinoma) or the lobules (Lobular carcinoma) that supply the ducts with milk. There is also rare cases that breast cancer starts in other areas of the breast. In 2010, over 250,000 new cases of breast cancer were expected to be diagnosed in women in the U.S. alone and the risk of getting invasive breast cancer during life time of a women is 1/8.
Indole-3-carbinol may act NAG-1 modulators involved in natural products-induced NAG-1 transcriptional signaling pathway used in prevention and treatment of cancer(1). According to the University of Urbino "Carlo Bo",, The indole-3-carbinol cyclic tetrameric derivative (CTet) inhibited breast cancer cell proliferation by endoplasmic reticulum stress and autophagy-related cell death induction, AKT(2). In human breast cancer cell lines MCF-7 and MDA-MB-231, the derivative also enhances ER stress response, as the main upstream molecular mechanism through which CTet acts in both hormone-responsive and triple-negative breast cancer cells(3). In support to the above, the study of University of Urbino Carlo Bo, Urbino (PU),  showed that the derivative may also be a potential anticancer combination agent for both hormone-responsive and triple-negative breast tumors(4).

References

(1) Nonsteroidal anti-inflammatory drug activated gene-1 (NAG-1) modulators from natural products as anti-cancer agents by Yang MH¹, Kim J², Khan IA³, Walker LA⁴, Khan SI⁵.(PubMed)
(2) The Indole-3-carbinol cyclic tetrameric derivative CTet synergizes with cisplatin and doxorubicin in triple-negative breast cancer cell lines by De Santi M¹, Galluzzi L, Duranti A, Magnani M, Brandi G.(PubMed)
(3) Induction of endoplasmic reticulum stress response by the indole-3-carbinol cyclic tetrameric derivative CTet in human breast cancer cell lines by Galluzzi L¹, De Santi M, Crinelli R, De Marco C, Zaffaroni N, Duranti A, Brandi G, Magnani M(PubMed)
(4) Antitumoral activity of indole-3-carbinol cyclic tri- and tetrameric derivatives mixture in human breast cancer cells: in vitro and in vivo studies by Brandi G¹, Fraternale A, Lucarini S, Paiardini M, De Santi M, Cervasi B, Paoletti MF, Galluzzi L, Duranti A, Magnani M.(PubMed).

2.  Lung cancer
Lung cancer is defined as a condition of the abnormal growth of the cells in the lung's tissue. Most common form of primary lung cancers are derived from epithelial cells. In Us, Lung cancer is the leading cause of cancer deaths, causing 158,683 people deaths, including 88,329 men and 70,354 women, according to 2007 statistic.
In mice study, Indole-3-carbinol showed to inhibit ling cancer via modulation of the receptor tyrosine kinase/PI3K/Akt signaling pathway(1), in dose dependent manner(2), In support of the above, the study by Medical College of Soochow University, indicated that I3C reduces radiosensitivity of lung cancer cells by mediating EGFR expression, indicating that EGFR may be an important target for I3C-mediated radioresistance in lung cancer. In deed, the individual of indole-3-carbinol or silibinin, showed to inhibit 43 and 36% reductions, respectively, in the multiplicity of tumors on the surface of the lung and 83 and 50% reductions, respectively, and mixtures of I3C and silibinin are more potent than the individual compounds for the chemoprevention of lung cancer in A/J mice, according to University of Minnesota(4).


References
(1) Indole-3-carbinol inhibited tobacco smoke carcinogen-induced lung adenocarcinoma in A/J mice when administered during the post-initiation or progression phase of lung tumorigenesis by Qian X¹, Melkamu T, Upadhyaya P, Kassie F.(PubMed)
(2) Dose-dependent inhibition of tobacco smoke carcinogen-induced lung tumorigenesis in A/J mice by indole-3-carbinol by Kassie F¹, Matise I, Negia M, Upadhyaya P, Hecht SS.(PubMed)
(3) [EGFR-dependent impact of indol-3-carbinol on radiosensitivity of lung cancer cells].

[Article in Chinese] by Xiao X¹, Meng Q, Xu J, Jiao Y, Rosen EM, Fan S.(PubMed)

(4) Enhanced inhibition of lung adenocarcinoma by combinatorial treatment with indole-3-carbinol and silibinin in A/J mice by Dagne A¹, Melkamu T, Schutten MM, Qian X, Upadhyaya P, Luo X, Kassie F.(PubMed)

 

 

3. Pancreatic cancer

Cancer of pancreas or pancreatic cancer is defined as condition of a malignant neoplasm of the pancreas, as the cells have become cancerous and divided uncontrollably. Most pancreatic cancers start in the ducts (exocrine component of the pancreas) that carry pancreatic juices with cancer of an epithelium that originates in glandular tissue accounts for over 75 - 90% of all cases of exocrine cancers.

I3C would be effective for enhancing sensitivity of pancreatic cancer cells to gemcitabine via down-regulation of miR-21, according to the Seoul National University College of Medicine(1). Indole-3-carbinol (I3C) also showed to lower the LD(50) of gemcitabine (Gemzar) in decreasing growth of both male (MiaPaca2) and female (SU86.86) pancreatic cancer cells, according to ¹FDA/National Center for Toxicological Research(2). In pancreatic cell lines, ther phytochemical showed to induced gemcitabine cytotoxicity, through up-regulation of hENT1 expression involved in the additive effect of I3C and gemcitabine(3).

 

 

References

(1) Chemosensitivity induced by down-regulation of microRNA-21 in gemcitabine-resistant pancreatic cancer cells by indole-3-carbinol by Paik WH¹, Kim HR, Park JK, Song BJ, Lee SH, Hwang JH.(PubMed)

(2) Gender differences in gemcitabine (Gemzar) efficacy in cancer cells: effect of indole-3-carbinol. by Lyn-Cook BD¹, Mohammed SI, Davis C, Word B, Haefele A, Wang H, Hammons G.(PubMed)

(3) Enhanced efficacy of gemcitabine by indole-3-carbinol in pancreatic cell lines: the role of human equilibrative nucleoside transporter 1 by Wang H¹, Word BR, Lyn-Cook BD.(PubMed)

 

 

4. Prostate cancer

Prostate cancer is defined as a condition in which the cells of prostate has become cancerous, causing abnormal cell growth which spread to the distant parts of the body. Most prostate cancers are slow growing and enlarged prostate and prostate cancer may be detected during the Physical (rectum) exams.

Indole-3-carbinol, has showed a strong evidence in supporting the use of  phytochemicals as epigenetic modulators for prostate cancer chemoprevention(1). Indole-3-carbinol (I3C), a common phytochemical in cruciferous vegetables, inhibited prostate cancer through induced G1 cell-cycle arrest and apoptosis in prostate cancer cells(2). In human PC-3 prostate cancer cell lines, the phytochemical also induced G1 cell cycle arrest of that leading to apoptosis, and regulates the expression of apoptosis-related genes(3). According to the Division of Cancer Prevention, National Cancer Institute, broccoli-derived compounds indole-3-carbinol (I3C) and 3,3'-diindolylmethane (DIM), showed to inhibit prostate cancer through modulation of the effect of androgen on CCL2-mediated pathways(4).

 

 

references

(1) Phytochemicals from cruciferous vegetables, epigenetics, and prostate cancer prevention. by W Watson G¹, M Beaver L, E Williams D, H Dashwood R, Ho E.(PubMed)

(2) Indole-3-carbinol and prostate cancer by Sarkar FH¹, Li Y.(PubMed)

(3) Indole-3-carbinol (I3C) induced cell growth inhibition, G1 cell cycle arrest and apoptosis in prostate cancer cells by Chinni SR¹, Li Y, Upadhyay S, Koppolu PK, Sarkar FH.(PubMed)

(4) Indole-3-carbinol and 3',3'-diindolylmethane modulate androgen's effect on C-C chemokine ligand 2 and monocyte attraction to prostate cancer cells by Kim EK¹, Kim YS, Milner JA, Wang TT.(PubMed)

4.
Dietary indole-3-carbinol (I3C) prevents the development of estrogen-enhanced cancers including breast, endometrial and cervical cancers(1) due to it antitumor activities associated not only with its regulation of estrogen activity and metabolism, but also its modulation of ER transcription activity(2) through both antiestrogenic and estrogenic activity(3). In human cervical cancer cells, in comparison to diindolylmethane (DIM), a major in vivo product of indole-3-carbinol (I3C), both I3C and DIM caused accumulation of DNA strand breaks in three cervical cancer cell lines.  I3C  increased apoptosis in target tissues in vivo.(4). In mice study, according to the The Long Island Campus of Albert Einstein College of Medicine, showed to prevent the cervical-vaginal cancer promoted high doses of estrogen in these mices(5) and increased PTEN expression in the cervical epithelium of the transgenic mouse in vivo(6)

References
(1) Indole-3-carbinol is a negative regulator of estrogen by Auborn KJ¹, Fan S, Rosen EM, Goodwin L, Chandraskaren A, Williams DE, Chen D, Carter TH.(PubMed)
(2) Indole-3-carbinol is a negative regulator of estrogen receptor-alpha signaling in human tumor cells. by Meng Q¹, Yuan F, Goldberg ID, Rosen EM, Auborn K, Fan S.(PubMed)
(3) Indolo[3,2-b]carbazole: a dietary-derived factor that exhibits both antiestrogenic and estrogenic activity by Liu H¹, Wormke M, Safe SH, Bjeldanes LF.(PubMed)
(4) Indole-3-carbinol and diindolylmethane induce apoptosis of human cervical cancer cells and in murine HPV16-transgenic preneoplastic cervical epithelium by Chen DZ¹, Qi M, Auborn KJ, Carter TH.(PubMed)
(5) Indole-3-carbinol prevents cervical cancer in human papilloma virus type 16 (HPV16) transgenic mice by Jin L¹, Qi M, Chen DZ, Anderson A, Yang GY, Arbeit JM, Auborn KJ.(PubMed)
(6) Indole-3-carbinol prevents PTEN loss in cervical cancer in vivo by Qi M¹, Anderson AE, Chen DZ, Sun S, Auborn KJ.(PubMed)

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