Levistolide A Induces Apoptosis via ROS-Mediated ER Stress Pathway in Colon Cancer Cells.

Abstract

BACKGROUND/AIMS:

Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Levistolide A (LA), a natural compound isolated from the traditional Chinese herb Ligusticum chuanxiong Hort, is used for treating cancer. In this study, we investigated the anticancer effect of LA in HCT116 and its isogenic p53-/- colon cancer cells, as well as the underlying mechanisms.

METHODS:

MTT assay was used to evaluate the effect of LA on the viability of cancer cells. Apoptosis and reactive oxygen species (ROS) production by the cells were determined by flow cytometry. Protein expression was detected by western blotting.

RESULTS:

The results showed that LA inhibited viability and caused apoptosis of both wild-type and p53-/- HCT116 cells. LA was able to trigger production of ROS and endoplasmic reticulum (ER) stress. Inhibition of ROS using N-acetylcysteine abrogated LA-induced ER stress and apoptosis, as well as the reduction in cancer cell viability.

CONCLUSION:

Our results indicate that LA causes apoptosis of colon cancer cells via ROS-mediated ER stress pathway. It will be interesting to develop the natural compound for chemotherapy of cancers such as CRC.

• Authors: Yingjuan Yang, Yanhua Zhang, Lan Wang, Shaochin Lee
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 42 Issue 3 Pg. 929-938 ( 2017) ISSN: 1421-9778 [Electronic] Germany
• PMID: 28662507 (Publication Type: Journal Article)
• Copyright: © 2017 The Author(s). Published by S. Karger AG, Basel.

Chemical References

• Antineoplastic Agents, Phytogenic
• Benzofurans
• Reactive Oxygen Species
• levistolide A

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis (drug effects)
• Benzofurans (pharmacology)
• Colon (drug effects, metabolism, pathology)
• Colonic Neoplasms (drug therapy, metabolism, pathology)
• Endoplasmic Reticulum Stress (drug effects)
• HCT116 Cells
• Humans
• Reactive Oxygen Species (metabolism)