New York, July 2 :
An Indian-origin researcher at the University of Minnesota has discovered that triptolide — an extract of the Chinese herb thunder god vine (tirpterygium wilforii) — suppresses a key protein that helps pancreatic cancer cells thrive.
GRP78, a protein that protects cells from dying, is more abundant in cancer cells and tissue than in normal organs and is thought to play a role in helping pancreatic cancer cells survive and thrive.
“Our study shows that although increased expression of GRP78 confers a survival advantage to the tumour cells, prolonged exposure to triptolide induces chronic endoplasmic reticulum (ER) stress that eventually leads to cell death,” Prof. Ashok Saluja said.
In this context, inhibition of GRP78 by activation of the ER stress pathway by triptolide offers a novel mechanism for inhibiting the growth and survival of pancreatic cancer cells, he noted.
For mammals to use the proteins in our bodies, a process called protein folding must occur in the endoplasmic reticulum (ER) of cells. If proteins are not folded fast enough, unfolded proteins begin to build up and the cell becomes stressed.
Prolonged ER stress activates a cellular process called the “unfolded protein response (UPR)”.
Initially, the UPR helps kick-start the cell’s protein-folding ability, allowing it to function properly again. But if the problem does not resolve, the UPR triggers cell death.
GRP78 helps cells survive long enough for the UPR to kick in and correct protein-folding problems.
“However, GRP78 is available in higher quantities in pancreatic cancer cells, which assists the cancer cells in evading cell death, allowing them to live and multiply,” researchers stressed.
The study was published in the Journal of Physiology-Gastrointestinal and Liver Physiology.