Anticancer activity of sugiol against ovarian cancer cell line SKOV3 involves mitochondrial apoptosis, cell cycle arrest and blocking of the RAF/MEK/ERK signalling pathway

Abstract

Introduction : Ovarian cancer is one of the leading causes of cancer-related deaths in women. Treatments for ovarian cancer include surgery followed by chemotherapy. However, the survival rate for ovarian cancer is still not satisfactory. Moreover, the current chemotherapy has numerous associated side effects. Therefore there is an urgent need to look for novel and more viable treatment options. Against this backdrop the present study was designed to evaluate the anticancer activity of sugiol against ovarian cancer cells. Material and methods : Cell viability was assessed by CCK8 assay, apoptosis by DAPI, AO/ER and annexin V/PI staining. Mitochondrial membrane potential and cell cycle analysis was performed by flow cytometry. Cell migration was investigated by wound healing assay. Protein expression was monitored by western blotting. Results : The results of the present study indicated that sugiol exerts significant (p < 0.0001) anticancer effects on SKOV3 cancer cells with an IC50 of 25 µM. However, sugiol exhibited less cytotoxicity against normal ovarian cells with an IC50 of 62.5 µM. The anticancer effects of sugiol were found to be due to G0/G1 cell cycle arrest and mitochondrial apoptosis. Sugiol also inhibited cell migration of SKOV3 cells dose dependently. Moreover, the results showed that sugiol could inhibit the RAF/MEK/ERK signalling pathway in a dose-dependent manner. Conclusions : The results of the present study indicate that sugiol exerts potent anticancer effects on SKOV3 cells via induction of cell cycle arrest, mitochondrial apoptosis and inhibition of the RAF/MEK/ERK signalling pathway.

Keywords

• ovarian cancer
• cell cycle arrest
• apoptosis
• raf/mek/erk
• cell migration