Hedychium spicatum rhizome essential oil induces apoptosis in human prostate adenocarcinoma PC-3 cells via mitochondrial stress and caspase activation

Abstract

Hedychium spicatum is an essential oil bearing plant extensively used in the traditional system of medicine in several countries. Previous research has revealed H. spicatum essential oil (HSEO) to exhibit anti-tumor activity, although the mechanism of action is still unknown. Therefore, the current study was designed to carry out a comprehensive characterization of HSEO and evaluate the chemotherapeutic potential of HSEO against cancerous cells. The volatile constituents of HSEO was determined by one-dimensional gas chromatography with time-of-flight mass spectrometry (GC-TOFMS) and two-dimensional gas chromatography with time-of-flight mass spectrometry (GCxGC-TOFMS). In total, 193 phytocompounds could be detected, out of which 140 were identified for the first time. The major phytoconstituents detected by GCxGC-TOFMS were β-pinene (10.94%), eucalyptol (6.45%), sabinene (5.48%) and trans-isolimonene (5.00%). GCxGC-TOFMS analysis showed two and half fold increase in the constituents over GC-TOFMS due to better chromatographic separation of constituents in the 2nd dimensional column. HSEO was tested for in vitro cytotoxic activity against cancerous (PC-3, HCT-116 and A-549) and normal (3T3-L1) cell, with HSEO being most selective for prostate cancer cell (PC-3) over non-tumorigenic fibroblast (3T3-L1) cell. HSEO treatment inhibited the colony formation ability of PC-3 cells. HSEO treatment caused apoptotic cell death and cell cycle arrest at G2/M and S phase in PC-3 cells. HSEO induced apoptosis via intracellular ROS accumulation, mitochondria depolarization and increased caspase-3, 8, and 9 levels in PC-3 cells. Additionally, HSEO treatment led to a decrease of Bcl-2 and Bcl-xL and increase of Bax and Bak protein levels. Overall, results from this study highlighted the anticancer potential of H. spicatum essential oil, which could be considered as a new agent for treating prostate cancer.