Molecular mechanism of apoptosis induction in skin cancer cells by the centipedegrass extractReport as inadecuate




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BMC Complementary and Alternative Medicine

, 13:350

Basic research

Abstract

BackgroundCentipedegrass extract CGE is mainly composed of maysin and its derivatives, which are recognized internationally as natural compounds. Compared to other flavonoids, maysin has a unique structure in that mannose is bound to the flavonoid backbone. CGE exhibits some biological properties in that it can function as an anti-oxidant, anti-inflammatory, anti-adipogenic, and insecticidal. Whether CGE has other biological functions, such as anti-cancer activity, is unknown.

MethodsB16F1 mouse and SKMEL-5 human cells were treated with CGE, and their subsequent survival was determined using MTT assay. We performed a cell cycle analysis using propidium iodide PI, and detected apoptosis using double staining with annexin V-FITC-PI. In addition, we examined mitochondrial membrane potentials using flow cytometry, as well as signaling mechanisms with an immunoblotting analysis.

ResultsCGE inhibited skin cancer cell growth by arresting the cell cycle in the G2-M phase, and increased both early and late apoptotic cell populations without affecting normal cells. Furthermore, we observed mitochondrial transmembrane depolarization, increased cytochrome-c release, caspase-3 and caspase-7 activation, and increased poly ADP-ribose polymerase degradation. CGE also downregulated activation of p-AKT, p-glycogen synthase kinase-3β GSK-3β, and p-BAD in a time-dependent manner. LY294002 inhibition of phosphoinositide 3-kinase PI3K significantly sensitized skin cancer cells, which led to an increase in CGE-induced apoptosis.

ConclusionsCGE controlled skin cancer cell growth by inhibiting the PI3K-AKT-GSK-3β signaling pathway and activating the effector caspases. This study is the first to demonstrate anti-cancer properties for CGE, and that CGE may be an effective therapeutic agent for treating skin cancer.

KeywordsCentipedegrass extract Apoptosis B16F1 SKMEL-5 PI3K-AKT-GSK-3β Caspase Skin cancer AbbreviationsCGECentipede grass extract

PI3KPhosphoinositide 3-kinase

MTT3-4, 5-dimethylthiazol-2-yl-2, 5-di-phenyltetrazolium bromide

GSK3βGlycogen synthase kinase-3 beta

PIPropidium iodide

PARPPoly-ADP-ribose-polymerase

PVDFPolyvinyl difluoride

DiOC6 33, 30-dihexyloxacarboxyanine iodide

DMSODimethyl sulphoxide

FITCFluorescein isothiocyanate.

Srilatha Badaboina, Hyoung-Woo Bai contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1186-1472-6882-13-350 contains supplementary material, which is available to authorized users.

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Author: Srilatha Badaboina - Hyoung-Woo Bai - Chul-Hong Park - Dong Min Jang - Bo Yun Choi - Byung Yeoup Chung

Source: https://link.springer.com/



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