Abstract
Background:Cervical cancer is the most common cancer and has the highest morbidity rate of gynaecological malignancies in women worldwide. So, the development of effective anti-cancer agents to treat this condition is vital. Considering the recent interest in free (unconjugated) curcuminoids delivery, the present study investigated the efficacy of a novel food-grade, free-curcuminoids (curcumin-galactomannoside complex; CGM) on cervical cancer cells (HeLa) of human origin. In this study, we examined the anticancer potential of CGM as well as its effects on the cell cycle and the apoptosis of HeLa cancer cell. Methods:Determination of anti-proliferative and apoptosis validation of CGM on HeLa cells was performed by 3-(4,5-Dimethylthiazol-2-yl)-2, 5,-diphenyltetrazolium bromide (MTT), acridine orange/propidium iodide and annexin-V-fluorescein isothiocyanate assays. Measurement of Reactive Oxygen Species (ROS) production, Caspase activities and protein expression experiments were performed to investigate the potential mechanisms of action in the apoptotic process. Results:The cytotoxic assays revealed that the CGM showed inhibition of cell survival and exhibited high cytotoxic activity against HeLa cells at 25 μg/mL. Further studies on morphological changes were done in CGM-treated cervical cancer cells contributing to apoptosis. Flow cytometry analysis with Annexin V-FITC and PI staining precisely indicated that CGM induced apoptosis in HeLa cell lines at 25 μg/mL. By the supplementation of CGM showed an increase in Bax and cleaved caspase-8 protein in HeLa cells after 48 h exposure. Conclusion:The evidence obtained from this study suggests that CGM is a potent and promising natural formulation against cervical cancer cells via induction of apoptosis through ROS mediated mitochondrial damage in HeLa cells. Hence, CGM could be further explored as a potential lead in treating cancer.
Highlights
Cancer is a major life-threatening disease and one of the foremost stimuli of death all over the world
The key results obtained by MTT and Neutral Red Uptake (NRU) assays in HeLa cells exposed to 5 μg/ml to 100 μg/ml for 24 h are summarized in Figures 1(A) and 1(B)
Scientists and researchers are giving more attention to alternative therapies and medicines to provide better treatment for cancer diseases owing to the fact that, most of the cancer therapies and medicines using for cancer patients have severe side-effects
Summary
Cancer is a major life-threatening disease and one of the foremost stimuli of death all over the world. Cervical Cancer (CC) is the one that stands in the third position worldwide and the fourth leading cause of death from gynaecologic malignancy. During the HPV infection, its genome gets integrated into the host body, which further leads to dysregulation of the cellular processes including cell proliferation, alteration of growth and differentiation factors, DNA synthesis, and oxidative stress and eventually leads to CC formation. We examined the anticancer potential of CGM as well as its effects on the cell cycle and the apoptosis of HeLa cancer cell. Further studies on morphological changes were done in CGM-treated cervical cancer cells contributing to apoptosis. Conclusion: The evidence obtained from this study suggests that CGM is a potent and promising natural formulation against cervical cancer cells via induction of apoptosis through ROS mediated mitochondrial damage in HeLa cells. CGM could be further explored as a potential lead in treating cancer
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