Jul 3 2018
Celastrol Induces Apoptosis in Gefitinib-Resistant Non-Small Cell Lung Cancer Cells via Caspases-Dependent Pathways
Dr. Elaine Lai-Han Leung et al reported a new compoundas apotential highly effectiveanti-cancer reagent in treatment of NSCLC .
Our knowledge about molecular mechanisms for oncogene-driven tumors and about resistance to targeted therapies has increased quickly over the past year. As a result, several regulatory approvals of new agents that significantly improve survival and quality of life for patients with lung cancer who have advanced disease have occurred. Targeting EGFR continues to be an active area of clinical trials and novel drug development. Gefitinib, the first-generation of targeted drug approved by FDA, which is a tyrosine kinase inhibitor (TKI) can specifically inhibit EGFR and its downstream survival signaling pathway. Despite the good initial significant response of TKI, like other chemotherapeutic agents, patients most acquire resistance to TKI eventually. Therefore, it is high time to discover more effective potential agents as candidate drugs for treating gefitinib resistant NSCLC patients. Inspired by multi-targeted effects of Celastrol, Dr. Leung Lai-Han and their team from the State Key Laboratory of Quality Research in Chinese Medicine (Macau University of Science and Technology, MUST) try to pave the way to combine targeted-drugs and traditional Chinese medicine(TCM).
They discovered that in vitro studies celastrol, which is a cytotoxic agent, exhibits significant anti-cancer activity on gefitinib-resistant NSCLC cells, Celastrol exerted cytotoxicity by induction of caspase-dependent apoptosis and Hsp90 client protein degradation in two gefitinib-resistant NSCLC cell lines. Take together, findings in the current studies indicate that celastrol possesses significant apoptotic induction effects in gefitinib-resistant cells, and caspases activation and Hsp90 client protein degradation play important roles in this apoptotic process. Celastrol may potentially be developed as a promising agent for treatment of gefitinib-resistant NSCLC patients in the future.
It was a first attempt to combine traditional Chinese medicine and targeted-drugs in lung cancer fields. Their study provided evidences to support the potential role of celastrol as a targeted-therapeutic adjuvants for cancer treatment and therapy in NSCLC. This paper was published by the journal “Molecules” on March 9, 2014. The newly released Impact Factor for Molecules is 2.861 (Thomson Reuters, 2017).