Investigation of prunetrin induced G2/M cell cycle arrest and apoptosis via Akt/mTOR/MAPK pathways in hepatocellular carcinoma cellsopen access
- Authors
- Abusaliya, Abuyaseer; Bhosale, Pritam Bhagwan; Kim, Hun Hwan; Park, Min Yeong; Jeong, Se Hyo; Lee, Sijoon; Kim, Gon Sup
- Issue Date
- May-2024
- Publisher
- Elsevier Masson s.r.l.
- Keywords
- Apoptosis; Cell cycle arrest; Flavonoids; Hepatocellular carcinoma; HepG2 cells; Huh7 cells
- Citation
- Biomedicine and Pharmacotherapy, v.174
- Indexed
- SCIE
SCOPUS
- Journal Title
- Biomedicine and Pharmacotherapy
- Volume
- 174
- URI
- https://scholarworks.gnu.ac.kr/handle/sw.gnu/70204
- DOI
- 10.1016/j.biopha.2024.116483
- ISSN
- 0753-3322
1950-6007
- Abstract
- Hepatocellular carcinoma (HCC) stands as a leading cause of mortality, and despite recent advancements in the overall survival rates, the prognosis remains dismal. Prunetin 4-O-glucoside (Prunetrin or PUR), an active compound derived from Prunus sp., was explored for its impact on HepG2 and Huh7 cells. The cytotoxicity assessment revealed a notable reduction in cell viability in both cell lines, while exhibiting non-toxicity towards HaCaT cells. Colony formation studies underscored PUR's inhibitory effect on cell proliferation, dose-dependently. Mechanistically, PUR downregulated cell cycle proteins (CDC25c, Cdk1/CDC2, and Cyclin B1), inducing G2/M phase arrest, corroborated by flow cytometry. Western blot analyses exhibited dose-dependent cleavages of PARP and caspase 3, indicative of apoptosis. Treatment with the apoptotic inhibitor z-vmd-fmk provided evidence of PUR-induced apoptosis. Annexin V and PI flow cytometry further affirmed apoptotic induction. Enhanced expression of cleaved-caspase 9 and the pro-apoptotic protein Bak, coupled with reduced anti-apoptotic Bcl-xL, and affirmed PUR's induction of intrinsic apoptosis. Additionally, PUR activated the MAPK pathway, evidenced by elevated phospho p38 and phospho ERK expressions in both cell lines. Notably, a concentration-dependent decrease in mTOR and Akt expressions indicated PUR's inhibition of the Akt/mTOR pathway in HepG2 and Huh7 cells. These findings illuminate PUR's multifaceted impact, revealing its potential as a promising therapeutic agent against HepG2 and Huh7 cells through modulation of cell cycle, apoptosis, and key signaling pathways. © 2024
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