A triterpenoid from wild bitter gourd inhibits breast cancer cells.

Li-Yuan Bai,Chang-Fang Chiu,Po-Chen Chu,Wei-Yu Lin,Shih-Jiuan Chiu,Jing-Ru Weng

doi:10.1038/srep22419

Abstract

The antitumor activity of 3β,7β,25-trihydroxycucurbita-5,23(E)-dien-19-al (TCD), a triterpenoid isolated from wild bitter gourd, in breast cancer cells was investigated. TCD suppressed the proliferation of MCF-7 and MDA-MB-231 breast cancer cells with IC50 values at 72 h of 19 and 23 μM, respectively, via a PPARγ−independent manner. TCD induced cell apoptosis accompanied with pleiotrophic biological modulations including down-regulation of Akt-NF-κB signaling, up-regulation of p38 mitogen-activated protein kinase and p53, increased reactive oxygen species generation, inhibition of histone deacetylases protein expression, and cytoprotective autophagy. Together, these findings provided the translational value of TCD and wild bitter gourd as an antitumor agent for patients with breast cancer.

Highlights

The antitumor activity of 3β,7β,25-trihydroxycucurbita-5,23(E)-dien-19-al (TCD), a triterpenoid isolated from wild bitter gourd, in breast cancer cells was investigated
We first examined the antiproliferative effect of TCD in two breast cancer cell lines, MCF-7 and MDA-MB-231, using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay (Fig. 1B)
Increased reactive oxygen species (ROS) has been reported to be responsible for the anti-tumor activity of some phytochemicals including curcumin, resveratrol, and triterpenoids[22,23,24], we examined the ROS generation in MCF-7 cells treated with TCD (Fig. 4A)

Summary

Introduction

The antitumor activity of 3β,7β,25-trihydroxycucurbita-5,23(E)-dien-19-al (TCD), a triterpenoid isolated from wild bitter gourd, in breast cancer cells was investigated. TCD induced cell apoptosis accompanied with pleiotrophic biological modulations including down-regulation of Akt-NF-κB signaling, up-regulation of p38 mitogenactivated protein kinase and p53, increased reactive oxygen species generation, inhibition of histone deacetylases protein expression, and cytoprotective autophagy Together, these findings provided the translational value of TCD and wild bitter gourd as an antitumor agent for patients with breast cancer. The much progress beyond the chemotherapy and hormonal therapy, including strategies against human epidermal growth factor receptor and against angiogenesis, the 5-year overall survival rate of patients with metastatic breast cancer is around 22%. To further explore and validate the anti-tumor effect of wild bitter gourd, in the present study, we investigated the efficacy and underlying mechanisms of another triterpenoid, 3β ,7β ,25-trihydro xycucurbita-5,23(E)-dien-19-al (TCD; structure shown in Fig. 1A) against breast cancer cells. To the best of our knowledge, we demonstrated for the first time that TCD induced apoptotic death in breast cancer cells through Akt-NF-κ B signaling, reactive oxygen species (ROS) production, and histone deacetylase inhibition

Methods

Results

Discussion

Conclusion