Apigenin 7-O-glucoside promotes cell apoptosis through the PTEN/PI3K/AKT pathway and inhibits cell migration in cervical cancer HeLa cells. (December 2020)

• Record Type: Journal Article
• Authors: Liu, Miao-Miao; Ma, Run-Hui; Ni, Zhi-Jing; Thakur, Kiran; Cespedes-Acuña, Carlos L.; Jiang, Li; Wei, Zhao-Jun
• Is Part Of: Food and chemical toxicology. Volume 146(2020)
• Publication Date: 2020-12
• Subjects: Apigenin 7-O-Glucoside -- Cervical cancer -- Apoptosis -- Cell cycle -- Migration -- PTEN/PI3K/AKT pathway; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2020.111843
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: Epidemiologic evidence promote the inclusion of flavones in diet due to their inhibitory effects on certain types of cancers, particularly in women. Among the naturally occurring plant flavonoids, Apigenin 7-O-glucoside (AGL) is endowed with anti-inflammatory, anti-oxidant, and anti-cancer activities. However, its mechanism of action on cervical cancer, the fourth largest cancer in women, has not yet been clarified. In the current study, we have determined the effect of AGL on human cervical cancer cells and studied its molecular mechanism against cervical cancer. The results showed that AGL inhibited the proliferation of HeLa cells (IC50 was 47.26 μM at 48 h) by inducing apoptosis. Furthermore, AGL treatment caused G0/G1 phase arrest, reduced mitochondrial membrane potential (MMP), and upgraded intracellular ROS production. AGL could promote the release of cytochrome c by regulating Bcl-2 family proteins, and then activated caspase 9/3 to promote cell apoptosis. Moreover, AGL treatment promoted the expression of p16 INK4A, while inhibited the expression of Cyclin A/D/E and CDK2/6. At the same time in HeLa cells treated with AGL, the PTEN/PI3K/AKT pathway was inhibited in a concentration-dependent manner, and cell migration was also impeded correspondingly through the matrix metalloproteinase 2 and 9. Our study may provide a new research direction for harnessing the novel natural compounds in cervical cancer treatment. Graphical abstract: Image 1 Highlights: ➢ Apigenin 7-O-glucoside inhibited cervical cancer proliferation in Hela cells. ➢ Apigenin 7-O-glucoside promotes cell apoptosis through cell cycle arrest, mitochondrial, death receptor, and PTEN/AKT/PI3K signaling pathways. ➢ Apigenin 7-O-glucoside inhibits Hela cell migration through down-regulating MMP2/9.