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The apoptotic effect of hesperetin on human cervical cancer cells is mediated through cell cycle arrest, death receptor, and mitochondrial pathways
Author(s) -
Alshatwi Ali A.,
Ramesh E.,
Periasamy V.S.,
SubashBabu P.
Publication year - 2013
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.2012.01061.x
Subject(s) - apoptosis , hesperetin , cell cycle checkpoint , cell cycle , programmed cell death , apoptotic cell death , cancer research , microbiology and biotechnology , receptor , cervical cancer , chemistry , cancer , medicine , biology , pharmacology , biochemistry , flavonoid , antioxidant
Hesperetin, a flavonoid from citrus fruits, has several bioactivities such as anti‐inflammatory, antihypertensive, antiatherogenic effects. However, studies elucidating the role and the mechanism(s) of action of hesperetin in cervical cancer are sparse. In this study, we investigated the mechanism of the antiproliferative and apoptotic actions exerted by hesperetin on human cervical cancer S i H a cells. The viability of S i H a cells was evaluated using the MTT assay, apoptosis by acridine orange/ethidium bromide, propidium iodide, TUNEL assay, and A nnexin V ‐ C y3, cell cycle distribution and mitochondrial transmembrane potential using flow cytometry, and apoptotic marker genes using quantitative real‐time PCR . The treatment of S i H a cells with hesperetin ( IC 50, 650 μ m ) showed a marked concentration‐ and time‐dependent inhibition of proliferation and induced the G 2/ M phase in a dose‐dependent manner after 24 h. There was an attenuation of mitochondrial membrane potential with increased expression of caspase‐3, caspase‐8, caspase‐9, p53, B ax, and F as death receptor and its adaptor protein F as‐associated death domain–containing protein ( FADD ), indicating the participation of both death receptor– and mitochondria‐related mechanisms. Furthermore, hesperetin‐induced apoptosis was confirmed by TUNEL and A nnexin V ‐ C y3. This study shows that hesperetin exhibits a potential anticancer activity against human cervical cancer cell lines in vitro through the reduction in cell viability and the induction of apoptosis. Altogether, these data sustain our contention that hesperetin has anticancer properties and merits further investigation as a potential therapeutic agent.