Abstract 1014: Dihydrotanshione I induces caspase-independent cell death and autophagy in lung cancer cells

Abstract

Abstract In the present study the antitumor mechanism of dihydrotanshinone I (DHT) from Salvia miltiorrhiza Bunge was elucidated in lung cancer cells. DHT significantly exerted cytotoxicity and increased the apoptosis by Annexin V assay in NSCLC (A549 and H460 cells) and lung mesothelioma cells (H28, H2452, MSTO). Furthermore, DHT reduced clonogenic ability in A549 cells. Interestingly, DHT increased PARP cleavage, but no activation of caspase-9 and caspase-3, although caspase-8 and, 3 were partially activated. FACS analysis revealed that the pan-caspase inhibitor z-VAD-fmk increased apoptosis induced by DHT. Furthermore, MTT assay showed that z-VAD-fmk treatment did not block cell cytotoxicity induced by DHT. In contrast, DHT induced the features of autophagy, including formation of autophagosomes by immunofluorescence and an increase of LC3II level after DHT exposure. Treatment of 3MA, an inhibitor of autophagy, blocked the expression level of LC3II induced by DHT and induced cytoprotective autophagy in A549 cells. Taken together, our data suggest that DHT induces caspase-independent cell death and autophagy in lung cancer cells as a potent agent for lung cancer treatment. Citation Format: Sung-Hoon Kim, Gunho Won, Myoung Seok Jeong, Sang Wook Yoon, Jihyun Lee, Bonglee Kim, Eun Jung Sohn. Dihydrotanshione I induces caspase-independent cell death and autophagy in lung cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1014. doi:10.1158/1538-7445.AM2015-1014