Anti-tumor effects of atractylenolide I isolated from Atractylodes macrocephala in human lung carcinoma cell lines

• Published in: Molecules (Basel, Switzerland) Vol. 18; no. 11; pp. 13357 - 13368
• Main Authors: Liu, Huanyi, Zhu, Yajie, Zhang, Tao, Zhao, Zhenguo, Zhao, Yu, Cheng, Peng, Li, Hua, Gao, Hui, Su, Xiaomei
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29-10-2013; MDPI
• Subjects: Animals; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; Antineoplastic Agents, Phytogenic - therapeutic use; antitumor activity; Apoptosis; Apoptosis - drug effects; atractylenolide I; Atractylodes - chemistry; Atractylodes macrocephala; bcl-X Protein - metabolism; Carcinoma - drug therapy; Carcinoma - metabolism; Caspase 3 - metabolism; Caspase 9 - metabolism; Cell Line, Tumor; Cell Survival - drug effects; Cytotoxicity; Flow cytometry; Humans; Investigations; Lactones - chemistry; Lactones - pharmacology; Lactones - therapeutic use; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Mice; Mice, Nude; Mitochondria; Proteins; Proto-Oncogene Proteins c-bcl-2 - metabolism; Sesquiterpenes - chemistry; Sesquiterpenes - pharmacology; Sesquiterpenes - therapeutic use
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules181113357

Atractylenolide I (ATL-1) is the major sesquiterpenoid of Atractylodes macrocephala. This study was designed to investigate whether ATL-1 induced apoptosis in A549 and HCC827 cells in vitro and in vivo. In our results, ATL-1 significantly decreased the percentage of in vitro viability, in a dose-dependent manner. In addition, DAPI staining and flow cytometry tests demonstrated the induction of apoptosis by ATL-I. Western blot analysis indicated that the protein levels of caspase-3, caspase-9 and Bax were increased in A549 and HCC827 cells after ATL-I exposure; to the contrary, the expressions of Bcl-2, Bcl-XL were decreased after treatment with ATL-1. In the in vivo study, ATL-I effectively suppressed tumor growth (A549) in transplanted tumor nude mice with up-regulation of caspase-3, caspase-9, and Bax and down-regulation of Bcl-2 and Bcl-XL. In conclusion, our results demonstrated that ATL-I has significant antitumor activity in lung carcinoma cells, and the possible mechanism of action may be related to apoptosis induced by ATL-I via a mitochondria-mediated apoptosis pathway.