Tanshinone IIA Suppresses Non-Small Cell Lung Cancer Through Beclin-1-Mediated Autophagic Apoptosis
Shasha Bai,
Sainan Cui,
Wenhao Wen,
Elaine Lai-Han Leung,
Jing Bai,
Huiyuan Lin,
Yongfei Cui,
Lei Yang,
Zhongqiu Liu,
Yuan Zheng,
Rong Zhang
Affiliations
Shasha Bai
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
Sainan Cui
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
Wenhao Wen
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
Elaine Lai-Han Leung
State Key Laboratory of Quality Research in Chinese Medicine/Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau 999078, China
Jing Bai
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
Huiyuan Lin
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
Yongfei Cui
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
Lei Yang
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
Zhongqiu Liu
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
Yuan Zheng
Cardiothoracic Surgery Department, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510006, China; Corresponding authors.
Rong Zhang
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Corresponding authors.
It is necessary to develop a new strategy for treatment of lung cancer since it is the main cause of cancer death. Tanshinone IIA (Tan IIA), an active ingredient of a commonly used traditional Chinese herb Salvia miltiorrhiza, provides a new direction to develop a new strategy for the treatment. It has been found that Tan IIA could inhibit lung cancer in vitro and in vivo by inducing autophagic apoptosis. Tan IIA increased apoptotic cells and the expression of cleaved caspase 3 and cleaved caspase 9, decreased B-cell lymphoma-2 (Bcl-2)/Bcl-2 associated X protein (Bax) ratio in human non-small cell lung cancer (NSCLC) cell lines, which was promoted by an autophagy activator Rapamycin, and weaken by autophagy inhibitor 3-methyladenine (3-MA). In addition, Tan IIA induced more autophagosomes, up-regulated light chain 3β (LC-3B) I and LC-3B II conversion and less sequestosome 1 (SQSTM1/p62) expression, which cannot be weakened by the caspase 3 antagonist. Moreover, overexpression of LC-3B gene (LC3B) and downregulation of autophagic gene 5 (ATG5) further confirmed that Tan IIA induced autophagic apoptosis in NSCLC cell lines. Beclin-1 gene (BECN1) overexpression and silence attenuated the effects of Tan IIA, suggesting autophagic apoptosis that Tan IIA induced was dependent on Beclin-1. Overall, our study demonstrated a new treatment mechanism of Tan IIA and suggested that Tan IIA is a potential new anti-cancer therapeutic option.
