Ovarian cancer in vitamin A points of view

Kyle J. Norton(Draft article)

According to the information of national cancer institute, in 2013 Us alone. 22,240 women were diagnosed with the incidence of the disease with death of 14030.
Depending to the stage and grade of the cancer, chemotherapy such as cisplatin, carboplatin, paclitaxel, liposomal doxorubicin may be necessary to prevent the spread and recurrence of the cancer. 
Recommended intakes of vitamin A, according to  the Institute of Medicine of the National Academies (formerly National Academy of Sciences) is 600 µg daily as extremely high doses (>9000 mg) can be toxicity as causes of dry, scaly skin, fatigue, nausea, loss of appetite, bone and joint pains, headaches, etc.
Epidemiological studies, linking vitamin A in reduced risk of ovarian cancer have been inclusive(a)(b)(c)(d)(e)(f).
1. Retinols
According to Temple University School of Medicine, retinols, the natural and synthetic derivatives of vitamin A, showed to inhibit the growth of human ovarian cancer cells both in vivo and in culture, suppressed ovarian carcinoma cell growth and induce apoptosis in ovarian tumor cells(1). In all-trans-retinoic acid (ATRA) has shown to inhibit the growth of several ovarian tumor cell lines, other ovarian carcinoma cell lines, and its synthetic version AHPN/CD437 showed to induced apoptosis through at least in part via an RAR(retinoic acid receptor) pathway(2)(3). Other study suggested that a novel combination of ATRA and zoledronic acid significantly induced apoptosis of related cell death in both OVCAR-3 and MDAH-2774 ovarian cancer cell lines with fewer side effects as compared to conventional cytotoxic agents(4).
 Some researchers suggested that ovarian cancer may be as a result of impaired conversion of retinol to RA in ovarian cancer cells and decreased CRBP1(Cellular Retinol Binding Protein 1) protein expression in prophylactic oophorectomies(surgery that reduces risk of breast cancer and ovarian cancer) causing concomitant losses of vitamin A metabolism and CRBP1 expression of which contribute to ovarian oncogenesis(5). Rb2/p130, a  tumor suppressor protein with function in regulation of  cell cycle progression, treatment of ATRA in sensitive ovarian carcinoma CA-OV3 cells, shoed a dramatic increase in Rb2/p130 protein mediates growth arrest at G0/G1, but it failed to growth arrest, although Rb2/p130 is expressed at high levels in SK-OV3 cells(6)(7).

2. Carotenoids(beta-carotene, alpha-carotene, gamma-carotene and beta-cryptoxanthin) Carotenoids, plant pigments, converted to vitamin A after intake, play an important role in prevention and treatment of some diseases through it antioxidant effects. Fenretinide (4-HPR), a synthetic retinoid, showed to induce apoptosis through a signaling cascade starting from reactive oxygen species (ROS) generation and involving endoplasmic reticulum (ER) stress response, induces apoptosis(8) and may be used as a preventive agent in genetic mutation, such as BRCA-1 and 2 mutation carriers causes of ovarian cancer(9). According to the Medical University of Białystok, in the study of vitamin A variants in association with ovarian cancer risk, Among vitamin A family compounds retinol and carotenoids, but not retinoids, inhibited the growth of cancer cells in dose dependent manner on human ovary endometrioid cancer cell line CRL-11731(10). Other researchers suggested to use antioxidants, including vitamin A variants) with first-line chemotherapy in treatment for ovarian cancer. In 2 case of women with ovarian cancer treatment, antioxidants showed to improve the efficacy of chemotherapy when added adjunctively, to first-line chemotherapy(11)(12).

Taking altogether, Vitamin A and its variants may be effective in reduced risk and treatment of ovarian cancer, especially when use conjunction with chemotherapy. As always, overdoses can lead to toxic symptoms. Please make sure you follow the guideline of the Institute of Medicine of the National Academies.  



References
(a) Dietary intake and ovarian cancer risk: a systematic review by Crane TE¹, Khulpateea BR, Alberts DS, Basen-Engquist K, Thomson CA.(PubMed)
(b) Risk of ovarian carcinoma and consumption of vitamins A, C, and E and specific carotenoids: a prospective analysis by Fairfield KM¹, Hankinson SE, Rosner BA, Hunter DJ, Colditz GA, Willett WC.(PubMed)
(c) The role of antioxidants and vitamin A in ovarian cancer: results from the Women's Health Initiative by Thomson CA¹, Neuhouser ML, Shikany JM, Caan BJ, Monk BJ, Mossavar-Rahmani Y, Sarto G, Parker LM, Modugno F, Anderson GL.(PubMed)
(d) A randomized parallel-group dietary study for stages II-IV ovarian cancer survivors by Paxton RJ¹, Garcia-Prieto C, Berglund M, Hernandez M, Hajek RA, Handy B, Brown J, Jones LA.(PubMed)
(e) Association of dietary vitamin A, carotenoids, and other antioxidants with the risk of ovarian cancer by Tung KH¹, Wilkens LR, Wu AH, McDuffie K, Hankin JH, Nomura AM, Kolonel LN, Goodman MT.(PubMed)
(f) Identification of carotenoids in ovarian tissue in women by Czeczuga-Semeniuk E¹, Wolczynski S.(PubMed)
(1) Retinoids and ovarian cancer byZhang D¹, Holmes WF, Wu S, Soprano DR, Soprano KJ.(PubMed)
(2) Induction of apoptosis in ovarian carcinoma cells by AHPN/CD437 is mediated by retinoic acid receptors by Holmes WF¹, Dawson MI, Soprano RD, Soprano KJ.(PubMed)
(3) All trans retinoic acid and cancer by Siddikuzzaman¹, Guruvayoorappan C, Berlin Grace VM.(PubMed)
(4) Enhancing cytotoxic and apoptotic effect in OVCAR-3 and MDAH-2774 cells with all-trans retinoic acid and zoledronic acid: a paradigm of synergistic molecular targeting treatment for ovarian cancer by Karabulut B¹, Karaca B, Varol U, Muslu U, Cakar B, Atmaca H, Kisim A, Uzunoglu S, Uslu R.(PubMed)
(5) Vitamin A metabolism is impaired in human ovarian cancer by Williams SJ¹, Cvetkovic D, Hamilton TC.(PubMed)
(6) Characterization of alterations of Rb2/p130 tumor suppressor in all-trans-retinoic acid resistant SK-OV3 ovarian carcinoma cells by Fields AL¹, Soprano DR, Soprano KJ.(PubMed)
(7) Insulin receptor substrate-1 is an important mediator of ovarian cancer cell growth suppression by all-trans retinoic acid by Ravikumar S¹, Perez-Liz G, Del Vale L, Soprano DR, Soprano KJ.(PubMed)
(8) AF1q: a novel mediator of basal and 4-HPR-induced apoptosis in ovarian cancer cells by Tiberio P¹, Cavadini E, Callari M, Daidone MG, Appierto V(PubMed)
(9) Fenretinide (4-HPR): a preventive chance for women at genetic and familial risk? by Cazzaniga M¹, Varricchio C, Montefrancesco C, Feroce I, Guerrieri-Gonzaga A.(PubMed)
(10) Vitamin A family compounds, estradiol, and docetaxel in proliferation, apoptosis and immunocytochemical profile of human ovary endometrioid cancer cell line CRL-11731 by Czeczuga-Semeniuk E¹, Bielawski T, Lemancewicz D, Rusak M, Wołczyński S.(PubMed)
(11) The use of antioxidants with first-line chemotherapy in two cases of ovarian cancer by Drisko JA¹, Chapman J, Hunter VJ.(PubMed)
(12) The use of antioxidant therapies during chemotherapy by Drisko JA¹, Chapman J, Hunter VJ.(PubMed)