Phytochemical Indole-3-carbinol (I3C) and Cervical Cancer

By Kyle J. Norton

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.

Cervical cancer is malignant neoplasm of the cervix uteri or cervical area caused by abnormal cells growth with alternation of cells DNA. According to the American Cancer Society's, in 2014, 12,360 new cases of invasive cervical cancer will be diagnosed with the death of  4,020 patients. The risk of cervical cancer is higher in Hispanic women followed by African-Americans, Asians and Pacific Islanders, and whites(a).
Depending to the stage and grade of the cancer, if the cancer is found in the early stahe, hysterectomy may not be needed. Other while  after sugery, chemotherapy including Cisplatin, Fluorouracil (5-FU), Mitomycin, Paclitaxel, Ifosfamide, Carboplatin, Bevacizumab and radiotherapy may be necesary, but with certain side effects. Emerging suggestion of a healthy and balanced diet to improve high serum levels of antioxidants may reduce cervical neoplasia risk(b)(c)  but other suggested that the role of diet and nutrition in the etiology of cervical cancer is not yet resolved(d) and Catalan Institute of Oncology study showed statistically nonsignificant inverse associations were also observed for leafy vegetables, root vegetables, garlic and onions, citrus fruits, vitamin C, vitamin E and retinol for invasive squamous cervical cancer (ISC)(e).

Dietary indole-3-carbinol (I3C) prevented the development of estrogen-enhanced cancers including breast, endometrial and cervical cancers(1) due to its antitumor activities associated not only with  regulation of estrogen activity and metabolism, but also 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)
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References
(a) Cerical cancer (Amerrican cancer society)
(b) Diet and serum micronutrients in relation to cervical neoplasia and cancer among low-income Brazilian women by Tomita LY¹, Longatto Filho A, Costa MC, Andreoli MA, Villa LL, Franco EL, Cardoso MA; Brazilian Investigation into Nutrition and Cervical Cancer Prevention (BRINCA) Study Team.(PubMed)
(c) Associations of dietary dark-green and deep-yellow vegetables and fruits with cervical intraepithelial neoplasia: modification by smoking by Tomita LY¹, Roteli-Martins CM, Villa LL, Franco EL, Cardoso MA; BRINCA Study Team.(PubMed)
(d) Diet and the risk of in situ cervical cancer among white women in the United States by Ziegler RG¹, Jones CJ, Brinton LA, Norman SA, Mallin K, Levine RS, Lehman HF, Hamman RF, Trumble AC, Rosenthal JF, et al.(PubMed)
(e) Dietary factors and in situ and invasive cervical cancer risk in the European prospective investigation into cancer and nutrition study by González CA¹, Travier N, Luján-Barroso L, Castellsagué X, Bosch FX, Roura E, Bueno-de-Mesquita HB, Palli D, Boeing H, Pala V, Sacerdote C, Tumino R, Panico S, Manjer J, Dillner J, Hallmans G, Kjellberg L, Sanchez MJ, Altzibar JM, Barricarte A, Navarro C, Rodriguez L, Allen N, Key TJ, Kaaks R, Rohrmann S, Overvad K, Olsen A, Tjønneland A, Munk C, Kjaer SK, Peeters PH, van Duijnhoven FJ, Clavel-Chapelon F, Boutron-Ruault MC, Trichopoulou A, Benetou V, Naska A, Lund E, Engeset D, Skeie G, Franceschi S, Slimani N, Rinaldi S, Riboli E.(PubMed)
 (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)