Fucosterol exhibits selective antitumor anticancer activity against HeLa human cervical cell line by inducing mitochondrial mediated apoptosis, cell cycle migration inhibition and downregulation of m-TOR/PI3K/Akt signalling pathway

Abstract

Cervical cancer greatly contributes to cancer-associated mortalities worldwide. The growing incidence of cervical cancer is of primary concern, and has signaled the need for multiple treatment options. Despite preliminary responses to chemotherapy and/or surgical interventions, the tumors consistently relapse. Previously, natural products gained attention for their diverse bioactivities, which include however are not limited to, neuroprotective, antimicrobial and anticancer effects. The present study evaluated the anticancer activity of fucosterol against a panel of human cancer cell lines. Results indicated that fucosterol exhibited selective inhibitory activity against human HeLa cervical cancer cell line with an IC ₅₀ of 40 µM. Fucosterol also induced apoptosis in HeLa cells and prompted reactive oxygen species mediated alterations in mitochondrial membrane potential. It triggered cell cycle arrest of HeLa cells at G2/M check point and exerted inhibitory effects on cell migration. The activation of the phosphoinositide-3-kinase (PI3K)/AKT Serine/Threonine Kinase 1 (AKT)/mechanistic target of Rapamycin (mTOR) pathway is important in cancer tumorigenesis, progression and chemotherapy resistance. The results demonstrated that fucosterol significantly inhibited the expression levels of key proteins of the PI3K/Akt/mTOR signaling pathway. Overall, the results of the present study suggest that fucosterol may prove beneficial in the management of cervical cancer.