Cervical cancer in Vitamin A Points of View

 Kyle J. Norton

Vitamins form an important part in human diet. Epidemiological studies, linking vitamin A in reduced risk of cervical cancer have produced uncleared result(1)(5)(8)(9). But in certain studies, vitamin A in form of retinoids and carotenoids is effective in inhibition of cervical  cancer cell lines through many anti proliferative and apoptotic pathways.

Vitamin A is a general term of Vitamin A Retinol, retinal, beta-carotene, alpha-carotene, gamma-carotene, and beta-cryptoxanthin best known for its functions for vision health and antioxidant scavenger and essential for growth and differentiation of a number of cells and tissues.


1. The serum of vitamin A
In a total of 144 cervical cancer cases and 288 age-matched, hospital-based controls using unconditional logistic regression models showed a statistically lower mean dietary intakes of vitamin A compared to control(2). Other study found that serum and urine collected  are lower from12 women diagnosed with cervical intraepithelial neoplasia(3)(4)(4a). But the study of Nizam Institute of Medical Sciences, showed no correction of levels of vitamin A intake between cervical cancer patients and normal controls, in a total of total of 60 consecutive patients and 60 controls were enrolled from a referral hospital during the year 2004(6)(7).

2. Retinols
A combination of retinoids with histone deacetylase (HDAC) inhibitors effectively inhibited the growth of cervical cancer cells  due to the restore RARβ2 expression, associated with a significant upregulation of p21(CIP1) and p53 as well as a pronounced decrease in p-Stat3(10). In cervical cancer cells line HeLa and CaSki, All-trans retinoic acid (ATRA) derived from retinols, inhibited the proliferation of cervical cancer cells line HeLa but showed no effect on proliferation CaSki cells(11).
Other derivatives of retinols, all-trans and 9-cis retinoic acid induced profilerative activity of CaSki cells through cell cycle arrest via exhibited the increase in the level of immunophenotypic expression of wild type p53 and inhibited E6/E7 transcription(12). The study of composition of tea polyphenol, (-)-epigallocatechin gallate (EGCG) and retinoic acid (RA), showed to prevent cervical adenocarcinoma, though induced apoptosis and inhibited telomerase activity(13).

3. Carotenoids
According to the University of Arizona, in the analysis of cervical tissue (cancerous, precancerous, and noncancerous) samples obtained from 87 patients (age, 21-86 years), showed that maintaining an adequate serum concentration of beta-carotene may be necessary for the prevention of cervical cancer and precancer(14). Crocetin is a natural carotenoid dicarboxylic acid, inhibited the cell proliferation of Hela cells through cell cycle arrest via p53-dependent and -independent mechanisms(15). The Albert Einstein College of Medicine and Montefiore Medical Center study, showed a lower correction of mean plasma levels of carotenoids (beta-carotene, lycopene, and canthaxanthin), as well as alpha-tocopherol, in women with cervical intraepithelial neoplasia (CIN)and cervical cancer and suggested that antioxidant deficiency may be associated to the pathogenesis of CIN and carcinoma of the cervix(16). Dr. Harris RW, and the researcher team in the study of Cancer of the cervix uteri and vitamin A indicated that the strong correction of significantly reduced serum beta carotene concentrations in women with pre-invasive disease compared to the controls(17).

Taking altogether, Vitamin A may be associated to reduced risk and treatment of cervical cancer, but further studies are necessary to validate its effectiveness. maintaining the adequate levels of vitamin A may be a choice to prevent the onset of the disease. 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,

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References
(1) 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)
(2) Intakes of vitamin A, C, and E, and beta-carotene are associated with risk of cervical cancer: a case-control study in Korea by Kim J¹, Kim MK, Lee JK, Kim JH, Son SK, Song ES, Lee KB, Lee JP, Lee JM, Yun YM.(PubMed)
(3) Rapid HPLC method for the determination of vitamin A and E and cotinine concentration in human serum in women with CIN and cervical cancer by Bystrowska B¹, Gomółka E, Szczudrawa A, Brandys J, Pawlik M, Milewicz T, Dulińska-Litewka J, Jach R.(PubMed)
(4) A case-control study of nutrient status and invasive cervical cancer. I. Dietary indicators.

Herrero R¹, Potischman N, Brinton LA, Reeves WC, Brenes MM, Tenorio F, de Britton RC, Gaitan E.(PubMed)

(4a) Dietary risk factors for invasive and in-situ cervical carcinomas in Bangkok, Thailand by Shannon J¹, Thomas DB, Ray RM, Kestin M, Koetsawang A, Koetsawang S, Chitnarong K, Kiviat N, Kuypers J.(PubMed)

(5) Intakes of vitamin A, C, and E, and beta-carotene are associated with risk of cervical cancer: a case-control study in Korea(5)Kim J¹, Kim MK, Lee JK, Kim JH, Son SK, Song ES, Lee KB, Lee JP, Lee JM, Yun YM.(PubMed)

(6) Food consumption pattern in cervical carcinoma patients and controls by Labani L¹, Andallu B, Meera M, Asthana S, Satyanarayana L.(PubMed)
(7) Dietary micronutrients and cervical dysplasia in southwestern American Indian women by Buckley DI¹, McPherson RS, North CQ, Becker TM.(PubMed)
(8) Antioxidant vitamins and mineral supplementation, life span expansion and cancer incidence: a critical commentary by Dolara P¹, Bigagli E, Collins A.(PubMed)
(9) Vitamin A and risk of cervical cancer: a meta-analysis by Zhang X¹, Dai B, Zhang B, Wang Z.(PubMed)
(10) Combination of valproic acid and ATRA restores RARβ2 expression and induces differentiation in cervical cancer through the PI3K/Akt pathway by Feng D¹, Cao Z, Li C, Zhang L, Zhou Y, Ma J, Liu R, Zhou H, Zhao W, Wei H, Ling B.(PubMed)
(11) Proliferation of cells and expression of RARs, RXRs and HPV viral E6 and E7 proteins in cervical cancer cell lines after treatment with ATRA by Myga-Nowak M¹, Pacholska-Bogalska J, Kwaśniewski W, Kwaśniewska A, Goździcka-Józefiak A.(PubMed)
(12) The effect of all-trans and 9-cis retinoic acid on the steady state level of HPV16 E6/E7 mRNA and cell cycle in cervical carcinoma cells by Narayanan BA¹, Holladay EB, Nixon DW, Mauro CT.(PubMed)
(13) Antiproliferative effects of the major tea polyphenol, (-)-epigallocatechin gallate and retinoic acid in cervical adenocarcinoma by Yokoyama M¹, Noguchi M, Nakao Y, Ysunaga M, Yamasaki F, Iwasaka T.(PubMed)
(14) Concentrations of carotenoids, tocopherols, and retinol in paired plasma and cervical tissue of patients with cervical cancer, precancer, and noncancerous diseases by Peng YM¹, Peng YS, Childers JM, Hatch KD, Roe DJ, Lin Y, Lin P.(PubMed)
(15) Crocetin induces cytotoxicity and enhances vincristine-induced cancer cell death via p53-dependent and -independent mechanisms by Zhong YJ¹, Shi F, Zheng XL, Wang Q, Yang L, Sun H, He F, Zhang L, Lin Y, Qin Y, Liao LC, Wang X.(PubMed)
(16) Plasma levels of beta-carotene, lycopene, canthaxanthin, retinol, and alpha- and tau-tocopherol in cervical intraepithelial neoplasia and cancer by Palan PR¹, Mikhail MS, Goldberg GL, Basu J, Runowicz CD, Romney SL.(PubMed)
(17) Cancer of the cervix uteri and vitamin A byb Harris RW, Forman D, Doll R, Vessey MP, Wald NJ.(PubMed)