Essential Oils from Vitex agnus castus L. Leaves Induces Caspase-Dependent Apoptosis of Human Multidrug-Resistant Lung Carcinoma Cells through Intrinsic and Extrinsic Pathways

Abstract

Essential oil (EO) fractions of plants are complex mixtures of volatile compounds with broad-spectrum biological properties. In the current study, the EO content of Vitex agnus castus L. (VAC) leaves growing in the Aegean region of Turkey was extracted and identified. Then, VAC EOs were investigated for their potential antioxidant, cytotoxic and apoptotic effects in human H69AR multi-drug resistant cancer cells. EOs were isolated by hydrodistillation and chemical composition was determined by GC-MS. Cell viability was assessed via MTT and trypan blue assays. Antioxidant activity was evaluated by measuring the total antioxidant activity and free radical scavenging activity. Apoptosis was evaluated via DNA fragmentation and caspase 3/7 activity assays. Changes in the levels of apoptotic genes were determined by RT-qPCR. The results indicated strong antioxidant activity and cytotoxic effect on H69AR cancer cells but not on HEK-293 human normal cells indicating the tumor-specific effect. VAC EOs induced caspase 3/7 activation and apoptosis through triggering both extrinsic- and intrinsic-pathways by modulating Bcl-2, Bcl-XL, Bax, Bad, FADD, Caspase-8, Caspase-9, TRAIL R1/DR4 and TRAIL R2/DR5. This study revealed that VAC EOs may be a promising candidate in the development of novel therapeutic agents for multi-drug resistant lung cancer treatment.