A novel polysaccharide from Se-enriched Ganoderma lucidum induces apoptosis of human breast cancer cells.
The novel polysaccharide SeGLP-2B-1 isolated from Se-enriched Ganoderma lucidum, showed anti-proliferative activity towards several cancer cell lines in vitro. To investigate the antitumor mechanisms, the apoptotic effects of SeGLP-2B-1 in human breast cancer cells were studied, and the mechanism of this action was further elucidated. Cell apoptosis was detected by Annexin V/PI staining. Caspase activity was assayed using a caspase apoptosis detection kit. Western blot analysis was used to evaluate the levels of pro-caspase-3, -8, -9, PARP and cytochrome c expression. The results showed that SeGLP-2B-1 inhibited the growth of MCF-7 cells in a time- and dose-dependent manner. Typical characteristics of apoptosis were observed, including morphological changes, sub-G1 cells and DNA ladder formation. Further analysis showed that SeGLP-2B-1 treatment disrupted the mitochondrial membrane potential followed by an increase in the cytochrome c cytosolic levels. Sequentially, SeGLP-2B-1 increased the activities of caspase-9, -3 and poly (ADP-ribose) polymerase in a time-dependent manner, however, no obvious activation of caspase-8 was observed. Caspase-9 and caspase-3 inhibitor prevented SeGLP-2B-1-induced apoptosis, and the activities of caspases-3, -9 were significantly up-regulated by SeGLP-2B-1. Our studies suggest that SeGLP-2B-1 induces apoptosis via a mitochondria-mediated pathway.
Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, College of Life Science, Liaoning Normal University, Dalian, P.R. China. djshang@lnnu.edu.cn
Dejing
D
Shang
Yang
Y
Li
Che
C
Wang
Xiaomin
X
Wang
Zhi
Z
Yu
Xin
X
Fu
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology*; D020940:Reishi / Q000737:chemistry; D018036:Selenium Compounds / Q000494:pharmacology*
D000970:Antineoplastic Agents; D010936:Plant Extracts; D011134:Polysaccharides; D018036:Selenium Compounds