Abstract
Pachymic acid (PA) is a purified triterpene extracted from medicinal fungus Poria cocos. In this paper, we investigated the anticancer effect of PA on human chemotherapy resistant pancreatic cancer. PA triggered apoptosis in gemcitabine-resistant pancreatic cancer cells PANC-1 and MIA PaCa-2. Comparative gene expression array analysis demonstrated that endoplasmic reticulum (ER) stress was induced by PA through activation of heat shock response and unfolded protein response related genes. Induced ER stress was confirmed by increasing expression of XBP-1s, ATF4, Hsp70, CHOP and phospho-eIF2α. Moreover, ER stress inhibitor tauroursodeoxycholic acid (TUDCA) blocked PA induced apoptosis. In addition, 25 mg kg-1 of PA significantly suppressed MIA PaCa-2 tumor growth in vivo without toxicity, which correlated with induction of apoptosis and expression of ER stress related proteins in tumor tissues. Taken together, growth inhibition and induction of apoptosis by PA in gemcitabine-resistant pancreatic cancer cells were associated with ER stress activation both in vitro and in vivo. PA may be potentially exploited for the use in treatment of chemotherapy resistant pancreatic cancer.
Highlights
The high mortality rates of pancreatic cancer, one of the most lethal cancers worldwide, are the result of inadequate tools for early diagnosis and few therapeutic options [1]
It was reported that pancreatic cancer cell lines PANC-1 and MIA PaCa-2 were resistant to gemcitabine treatment [35,36,37]
The apoptosis inducting effects of Pachymic acid (PA) in gemcitabine-resistant PANC-1 and MIA PaCa-2 were determined by the induction of nuclear DNA fragmentation using ELISA [38]
Summary
The high mortality rates of pancreatic cancer, one of the most lethal cancers worldwide, are the result of inadequate tools for early diagnosis and few therapeutic options [1]. Gemcitabine, a cytotoxic nucleoside analogue, is the current clinical standard of care for advanced pancreatic cancer but has a response rate of less than 20% [2]. A potential novel strategy for highly treatmentresistant cancers is the induction of an organelle-related stress response, such as endoplasmic reticulum (ER), nuclear and mitochondrial stress response in cancer cells [3]. Natural Triterpene Inhibits Pancreatic Cancer salary for Dr Isaac Eliaz, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the ‘author contributions’ section
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
