Methylisoindigo preferentially kills cancer stem cells by interfering cell metabolism via inhibition of LKB1 and activation of AMPK in PDACs

Pancreatic ductal adenocarcinoma (PDAC) clinically has a very poor prognosis. No small molecule is available to reliably achieve cures. Meisoindigo is chemically related to the natural product indirubin and showed substantial efficiency in clinical chemotherapy for CML in China. However, its effect on PDAC is still unknown. Our results showed strong anti-proliferation effect of meisoindigo on gemcitabine-resistant PDACs. Using a recently established primary PDAC cell line, called Jopaca-1 with a larger CSCs population as model, we observed a reduction of CD133+ and ESA+/CD44+/CD24+ populations upon treatment and concomitantly a decreased expression of CSC-associated genes, and reduced cellular mobility and sphere formation.

Source: Molecular Oncology - February 3, 2016 Category: Cancer & Oncology Authors: Xinlai Cheng, Jee Young Kim, Shahrouz Ghafoory, Tijen Duvaci, Roya Rafiee, Jannick Theobald, Hamed Alborzinia, Pavlo Holenya, Johannes Fredebohm, Karl-Heinz Merz, Arianeb Mehrabi, Mohammadreza Hafezi, Arash Saffari, Gerhard Eisenbrand, Jörg D. Hoheisel, Source Type: research