Home
Resources
Publications
Selective Activation of Tumor-Suppressive MAPKP Signaling Pathway by Triptonide Effectively Inhibits Pancreatic Cancer Cell Tumorigenicity and Tumor Growth

Selective Activation of Tumor-Suppressive MAPKP Signaling Pathway by Triptonide Effectively Inhibits Pancreatic Cancer Cell Tumorigenicity and Tumor Growth

Bin Zhang, Mei Meng, Shufen Xiang, Zhifei Cao, Xingdong Xu, Zhe Zhao, Tong Zhang, Bowen Chen, Ping Yang, Ye Li, Quansheng Zhou

Biochem Pharmacol. 2019 Aug;166:70-81.

PMID: 31075266

Abstract:

The mitogen-activated protein kinase (MAPK, 1K) family members ERK, JNK, and p38 play a divergent role in either promoting tumorigenesis or tumor-suppression. Activation of ERK and JNK promotes tumorigenesis; whereas, escalation of p38 inhibits carcinogenesis. As these three MAPK members are controlled by the common up-stream MAPK signaling proteins which consist of MAPK kinases (2K) and MAPK kinase kinases (3K), how to selectively actuate tumor-suppressive p38, not concurrently stimulate tumorigenic ERK and JNK, in cancer cells is a challenge for cancer researchers, and a new opportunity for novel anti-cancer drug discovery. Using human pancreatic cancer cells and xenograft mice as models, we found that a small molecule triptonide first discerningly activated the up-stream MAPK kinase kinase MEKK4, not the other two 3K members ASK1 and GADD45; and then selectively actuated the middle stream MAPK kinase MKK4, not the other two 2K members MKK3 and MKK6; and followed by activation of the MAPK member p38, not the other two members ERK and JNK. These data suggest that triptonide is a selective MEKK4-MKK4-p38 axis agonist. Consequently, selective activation of the MEKK4-MKK4-p38 signaling axis by triptonide activated tumor suppressor p21 and inhibited CDK3 expression, resulting in cancer cell cycle arrest at G2/M phase and marked inhibition of pancreatic cancer cell tumorigenic capability in vitro and tumor growth in xenograft mice. Our findings support the notion that selective activation of tumor-suppressive MEKK4-MKK4-p38-p21signaling pathway by triptonide is a new approach for pancreatic cancer therapy, providing a new drug candidate for development of novel anti-cancer therapeutics.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP38647119	Triptonide		38647-11-9	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: