Effects of synthetic alkyl-phospholipid (Perifosine) on survival and cell cycle relevant genes of hepatocellular carcinoma cells

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality globally, particularly in Asia. Limited treatment options highlight the needs for novel therapies. Alkyl-phospholipids (ALPs) offer a promising alternative to traditional chemotherapy by targeting cell membrane integrity and signaling pathways rather than DNA replication. Perifosine, a synthetic ALP, has shown cytotoxic effects in cancer cells, but its mechanisms on cell cycle regulation in HCC require further investigation. Methods: This in vitro study evaluated the effects of perifosine on HepG2 liver cancer cells. Cytotoxicity of perifosine was assessed using the MTT assay while applying various concentrations over 24-, 48-, and 72-hours intervals. Gene expression analysis of cell cycle regulator genes (CCNA1, CCNA2, and CCND1) was conducted using qRT-PCR after treating the HepG2 cancer cells with perifosine at IC25, IC50, and IC75 concentrations for 48 hours. Results: Perifosine demonstrated time and dose dependent cytotoxicity, with increased cell death at higher concentrations and prolonged exposure. Perifosine exposure imposed discrete expression modifications in CCNA1, CCNA2 and CCNDI genes. Maximum de-regulation was observed for CNNA1 (8fold) and CCNA2 (-3.5fold) in response to perifosine exposure. Conclusion: Perifosine exhibited cytotoxic effects and imposed de-regulation in cell cycle related genes in liver cancer cells.