The simultaneous effect of valproic acid and gamma radiation on telomerase activity and bax and Bcl-2 protein levels in MCF-7 breast cancer cell line

Background: Breast cancer is one of the most prevalent types of cancer. Factors such as ionizing radiation and chemotherapeutic agents can trigger apoptosis and cancer cell death. An anticonvulsant drug named Valproic acid is a histone deacetylase inhibitor that shows promising anti-tumor effects in a variety of cancers. Telomerase is a ribonucleoprotein enzyme that activated in cancer cells and lead to telomeres shortening inhibition and triggering the apoptosis. Objectives: The purpose of this research was to investigate the simultaneously effect of Valproic acid and gamma radiation on telomerase activity and bax and Bcl-2 protein level in MCF-7 breast cancer cell line. Materials and Methods: MCF-7 cells was treated with different dose of Valproic acid (0, 2, 8 and 16 mM/l) and single dose of gamma radiation (4 Gy/min. (cell toxicity was determined using neutral uptake test. Telomerase activity was determined using TRAP assay (PCR-ELISA) method. Bax and Bcl-2 protein level was determined by ELISA method, as well. Results: Combination of Valproic acid and gamma radiation increased significantly cell toxicity in a time and dose dependent manner compared with control (P < 0.0001). The ratio of Bax/Bcl-2 was increased in a dose dependent manner at 48 and 72 hour treatment (P < 0.0001). There was a decrease in Telomerase activity after 24, 48 and 72 hours treatment in a dose dependent manner (P < 0.0001). Conclusions: The increasing cell toxicity, apoptosis-inducing effects and decreasing telomerase activity may play an important role in the Valproic acid and radiation mechanism. The current survey suggested that it is likely beneficial to combine Valproic acid and gamma radiation to treat breast cancer. © 2015, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences

Kisspeptin levels in relation to sex hormone profile among PCOS patients

Introduction: Polycystic ovary syndrome (PCOS) is a common endocrine disease among women in the reproductive age that is associated with consequences such as insulin resistance and hyperandrogenemia. This study was aimed to assess the association of sex hormone profile and kisspeptin levels in PCOS women in Gorgan, Iran. Methods: In this case-control study, 43 women with diagnosed PCOS between the ages of 15 and 37 years and 40 healthy demographically matched controls were recruited. Sex hormone profile and kisspeptin levels were measured in these subjects using ELISA assay kits. Results: Follicle stimulating hormone (FSH), sex hormone binding globulin (SHBG), and kisspeptin levels were significantly lower in cases than in controls. Luteinizing hormone (LH), free-testosterone (FT), 17-OH-progesterone (17-OH-P), dehydroepiandrosterone sulfate (DHEA-S), estradiol (E2), and free androgen index (FAI) were higher in PCOS significantly. There was a significant positive correlation between kisspeptin levels and LH and E2 in cases (p = 0.037 and p = 0.024, respectively). The results of the regression analysis have shown a significant association between the LH and kisspeptin concentrations in PCOS group (r = 0.275, p = 0.037). Conclusion: PCOS patients had lower plasma kisspeptin level that was positively correlated with LH and estradiol levels. Also, higher levels of free androgens were demonstrated in these patients. It is suggested that kisspeptin may be involved in complex interactions of the sex hormone endocrine system of PCOS. © 2021, Royal Academy of Medicine in Ireland