The synthetic flavonoid WYC02-9 inhibits colorectal cancer cell growth through ROS-mediated activation of MAPK14 pathway.

Abstract

AIM:

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. In this study, we explored the anti-cancer activity of WYC02-9, a synthetic protoapigenone, on human HCT116 CRC cells.

MAIN METHODS:

The anti-cancer activity of WYC02-9 and its underlying mechanisms were analyzed using XTT cell proliferation assays, colony formation assays, FACS analysis, annexin V staining, immunoblotting analysis, reactive oxygen species (ROS) generation assays, soft agar assays, a nude mice xenograft study and immunohistochemistry assays.

KEY FINDINGS:

Data showed that WYC02-9 suppressed CRC cell growth by arresting cells at G2/M and inducing cell death via apoptotic pathways. Further analysis demonstrated that WYC02-9-induced apoptosis was mediated by the activation of a ROS-mediated MAPK14 pathway. An in vivo xenograft study revealed that WYC02-9 enhanced MAP2K3/6 and MAPK14 phosphorylation, induced apoptosis, and suppressed CRC tumor growth.

SIGNIFICANCE:

WYC02-9 exerts its anti-tumor effect via ROS/MAPK14-induced apoptosis and has the potential to be developed as a chemotherapeutic agent for CRC.

• Authors: Yun-Ju Chen, Hsin-Pao Chen, Yu-Jen Cheng, Yu-Heng Lin, Kuang-Wen Liu, Yun-Ju Chen, Ming-Feng Hou, Yang-Chang Wu, Yi-Chen Lee, Shyng-Shiou Yuan
• Journal: Life sciences (Life Sci) Vol. 92 Issue 22 Pg. 1081-92 (Jun 13 2013) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 23624232 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Cyclohexanones
• Flavones
• Plant Extracts
• Reactive Oxygen Species
• protoapigenone
• Mitogen-Activated Protein Kinase 14

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Colorectal Neoplasms (drug therapy, metabolism, pathology)
• Cyclohexanones (pharmacology)
• Drug Screening Assays, Antitumor
• Female
• Flavones (pharmacology)
• Gene Knockdown Techniques
• Humans
• Mice
• Mice, Nude
• Mitogen-Activated Protein Kinase 14 (metabolism)
• Neoplasm Transplantation
• Plant Extracts (pharmacology)
• Reactive Oxygen Species (metabolism)
• Transplantation, Heterologous
• Xenograft Model Antitumor Assays