Title:Jaridonin, a Novel Ent-Kaurene Diterpenoid from Isodon rubescens, Inducing Apoptosis via Production of Reactive Oxygen Species in Esophageal Cancer Cells
Volume: 13
Issue: 6
Author(s): Yong-Cheng Ma, Yu Ke, Xiaolin Zi, Wen Zhao, Xiao-Jing Shi and Hong-Min Liu
Affiliation:
Keywords:
Apoptosis, ent-kaurene diterpenoid, esophageal cancer, mitochondria pathway, rabdosia rubescens, reactive
oxygen species.
Abstract: Isodon rubescens, a Chinese herb, has been used as a folk, botanical medicine in China for inflammatory
diseases and cancer treatment for many years. Recently, we isolated a new ent-kaurene diterpenoid, named Jaridonin,
from Isodon rubescens. The chemical structure of Jaridonin was verified by Infrared (IR), Nuclear magnetic resonance
(NMR), and Mass spectrum (MS) data as well as X-ray spectra. Jaridonin potently reduced viabilities of several
esophageal cancer cell lines, including EC109, EC9706 and EC1. Jaridonin treatment resulted in typical apoptotic
morphological characteristics, increased the number of annexin V-positive staining cells, as well as caused a G2/M arrest
in cell cycle progression. Furthermore, Jaridonin resulted in a significant loss of mitochondrial membrane potential,
release of cytochrome c into the cytosol, and then activation of Caspase-9 and -3, leading to activation of the mitochondria
mediated apoptosis. Furthermore, these effects of Jaridonin were accompanied by marked reactive oxygen species (ROS)
production and increased expression of p53, p21waf1/Cip1 and Bax, whereas two ROS scavengers, N-acetyl-L-cysteine (LNAC)
and Vitamin C, significantly attenuated the effects of Jaridonin on the mitochondrial membrane potential, DNA
damage, expression of p53 and p21waf1/Cip1 and reduction of cell viabilities. Taken together, our results suggest that a
natural ent-kaurenoid diterpenoid, Jaridonin, is a novel apoptosis inducer and deserves further investigation as a new
chemotherapeutic strategy for patients with esophageal cancer.
