Abstract
Xanthones are an important class of natural compounds bearing huge bioactivity profiles. Garcinone-E is one among most active xanthones showing potential anticancer activity against various human cancer cell lines. Therefore, the current study was performed to explore the anticancer potency of naturally occurring garcinone-E xanthone against human HeLa cervical cancer cells. The underlying mechanism of action was also tried to be explored via testifying its induction of programmed cell death, arrest of cell cycle, suppression of cell migration, cell invasion and cell adhesion. MTT assay was implemented to estimate the viability of HeLa cells after garcinone-E exposure and clonogenic assay was used to analyze the effect on clonogenic potential. Acridine orange/ethidium bromine (AO/EB) staining assay was performed for monitoring of programmed cell death along with western blotting. Flow cytometric studies were carried out to analyze cell cycle check points. Transwell chambers assays were carried out for studying the impact of garcinone-E on migration and invasion potency of HeLa cells. Western blotting was used to study the expressions of apoptosis linked proteins in HeLa cells. Results indicated that garcinone-E remarkably decreased the viability to minimum in HeLa cells in both dose and time-reliant manner. The clonogenic capacity of HeLa cells was efficiently reduced by garcinone exposure. AO/EB staining showed that the anti-viability action of garcinone-E was apoptosis allied which was supported by western blotting as well. The cell cycle check points study indicated cell cycle arrest at G2/M-phase. HeLa cell migration and invasion were reduced efficiently after being subjected to garcinone-E treatment in a dose reliant fashion. In conclusion, garcinone-E has a remarkable potential to act as anti-cervical cancer chemopreventive provided further in vivo studies are required.
Highlights
Natural products have long served human kind in copious aspects including food and medicine (Chen et al 2018)
Its effects of selective and potent anticancer activity mediated via inducing programmed cell death, G2/M phase cell cycle arrest and suppressing cellular migration, cell invasion and cell adhesion, was investigated
Proliferation rate in cervical cancer HeLa cells was analyzed through MTT assay after treatment with variant garcinoneE (Fig. 1) doses viz 0, 16, 64 and 128 μM for 24 h, 48 h and 72 h
Summary
Natural products have long served human kind in copious aspects including food and medicine (Chen et al 2018). Besides mangosteen contains several secondary metabolites, xanthones in particular have revealed efficient anticancer activity. Α-mangostin is a primary xanthone that has been extensively investigated but garcinone-E have revealed potential pharmacological and biological properties (Ho et al 2002). Garcinone-E has been reported to exert anticancer effects against different human cancer cell lines including colorectal, breast and hepatocellular carcinoma (Mohamed et al 2017). Cervical cancer (CC), is a dangerous life threatening and a frequent gynecological disorder prevalent in women, globally. It has been ranked as 4th lethal malignancy in women with approximately 0.27 million deaths in the year of 2015 (Bray et al 2018). Among all subtypes of cervical cancer, almost all include a major-risk factor of long HPV infection (human papillomavirus infection). Its effects of selective and potent anticancer activity mediated via inducing programmed cell death, G2/M phase cell cycle arrest and suppressing cellular migration, cell invasion and cell adhesion, was investigated
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