摘要

Ovarian cancer is one of the most common causes of mortality among all cancers in females and is the primary cause of mortality from gynecological malignancies. The objective of the current research work was to evaluate a naturally occurring sesquiterpene-delta-Cadinene for its antiproliferative and apoptotic effects on human ovary cancer (OVCAR-3) cells. We also demonstrated the effect of delta-Cadinene on cell cycle phase distribution, intracellular damage and caspase activation. Sulforhodamine B (SRB) assay was used to evaluate the antiproliferative effect of delta-cadinene on OVCAR-3 cells. Cellular morphology after delta-cadinene treatment was demonstrated by inverted phase contrast microscopy, fluorescence microscopy and transmission electron microscopy. Flow cytometry was used to analyze the effect of delta-cadinene on cell cycle phase distribution and apoptosis using propidium iodide and Annexin V-fluorescein isothiocyanate (FITC)/PI kit. The results revealed that delta-cadinene induced dose-dependent as well as time-dependent growth inhibitory effects on OVACR-3 cell line. delta-cadinene also induced cell shrinkage, chromatin condensation and nuclear membrane rupture which are characteristic of apoptosis. Treatment with different doses of delta-cadinene also led to cell cycle arrest in sub-G1 phase which showed dose-dependence. Western blotting assay revealed that delta-cadinene led to activation of caspases in OVCAR-3 cancer cells. PARP cleavage was noticed at 50 mu M dose of delta-cadinene with the advent of the cleaved 85-kDa fragment after exposure to delta-cadinene. At 100 mu M, only the cleaved form of PARP was detectable. Pro-caspase-8 expression remained unaltered until 10 mu M dose of delta-cadinene. However, at 50 and 100 mu M dose, pro-caspase-8 expression was no longer detectable. There was a significant increase in the caspase-9 expression levels after 50 and 100 mu M delta-cadinene treatments.