Underlying mechanisms of apoptosis in HepG2 cells induced by polyphyllin I through Fas death and mitochondrial pathways

Abstract

Aims: Polyphyllin I, a steroidal saponin in Rhizoma paridis, which possess broad application prospects in cancer prevention and treatment. The purpose of this study was to determine the potential cytotoxicity and mechanism of Polyphyllin I in HepG2 cells.

Main methods: In this study, we used MTT to evaluate cell survival. Cell apoptosis rate, cell cycle distribution, mitochondrial membrane potential and ros levels were measured by flow cytometry, and the expression of apoptosis-related proteins was determined by Western blot analysis.

Key findings: Polyphyllin I significantly reduced cell viability and induced HepG2 cell apoptosis in a dose and time-dependent manner. Compared with the control group, it could induce reactive oxygen species (ROS) generation and depolarization of matrix metalloproteinases in liver cells. Polyphyllin I dose-dependent increased the release of mitochondrial cytochrome c, and levels of Fas, p53, p21, and Bax/Bcl-2 ratios, as well as the activation of cleaved caspase-3, -8, -9, and subsequent cleavage of the poly (ADP-ribose) polymerase (PARP). The G2/M phase cell cycle arrest was induced by increasing the expression of p21 and cyclin E1, and significantly reducing the expression of cyclin A2 and CDK2.

Significance: Our results suggested that Polyphylin I inhibited cell proliferation and growth by triggering G2/M cell cycle arrest, and induced apoptosis through intracellular and extracellular apoptosis pathways to cause cell death by generating reactive oxygen species.

Keywords:

• Polyphyllin I
• cell apoptosis
• mechanisms
• reactive oxygen species
• toxicology

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability

The data used to support the findings of this study are available from the corresponding author upon request.

Additional information

Funding

This research was funded by the National Natural Science Foundation of China [No. 81703715] and the Beijing Natural Science Foundation [No. 7194289].

This research was funded by the National Natural Science Foundation of China [No. 81703715] and the Beijing Natural Science Foundation [No. 7194289].