Autophagy Accompanied with Bisdemethoxycurcumin-induced Apoptosis in Non-small Cell Lung Cancer Cells.
- Author:
Jin Hong XU
1
;
He Ping YANG
1
;
Xiang Dong ZHOU
1
;
Hai Jing WANG
1
;
Liang GONG
1
;
Chun Lan TANG
1
Author Information
- Publication Type:Journal Article
- Keywords: Apoptosis; Autophagy; Bisdemethoxycurcumin; Hedgehog pathway; Non-small cell lung cancer
- MeSH: Antineoplastic Agents; pharmacology; Apoptosis; drug effects; Autophagy; drug effects; Carcinoma, Non-Small-Cell Lung; drug therapy; Cell Line, Tumor; Curcumin; analogs & derivatives; chemistry; pharmacology; Down-Regulation; Gene Expression Regulation, Neoplastic; drug effects; Hedgehog Proteins; genetics; metabolism; Humans; Kruppel-Like Transcription Factors; genetics; metabolism; Signal Transduction; drug effects; Zinc Finger Protein GLI1
- From: Biomedical and Environmental Sciences 2015;28(2):105-115
- CountryChina
- Language:English
-
Abstract:
OBJECTIVETo investigate the effects of bisdemethoxycurcumin (BDMC) on non-small cell lung cancer (NSCLC) cell line, A549, and the highly metastatic lung cancer 95D cells.
METHODSCCK-8 assay was used to assess the effect of BDMC on cytotoxicity. Flow cytometry was used to evaluate apoptosis. Western blot analysis, electron microscopy, and quantification of GFP-LC3 punctuates were used to test the effect of BDMC on autophagy and apoptosis of lung cancer cells.
RESULTSBDMC inhibited the viability of NSCLC cells, but had no cytotoxic effects on lung small airway epithelial cells (SAECs). The apoptotic cell death induced by BDMC was accompanied with the induction of autophagy in NSCLC cells. Blockage of autophagy by the autophagy inhibitor 3-methyladenine (3-MA) repressed the growth inhibitory effects and induction of apoptosis by BDMC. In addition, BDMC treatment significantly decreased smoothened (SMO) and the transcription factor glioma-associated oncogene 1 (Gli1) expression. Furthermore, depletion of Gli1 by siRNA and cyclopamine (a specific SMO inhibitor) induced autophagy.
CONCLUSIONAberrant activation of Hedgehog (Hh) signaling has been implicated in several human cancers, including lung cancers. The present findings provide direct evidence that BDMC-induced autophagy plays a pro-death role in NSCLC, in part, by inhibiting Hedgehog signaling.
