Magnolol induces apoptosis via caspase-independent pathways in non-small cell lung cancer cells.
Magnolol, a hydroxylated biphenyl agent isolated from herbal planet Magnolia officinalis, is a component of traditional Asian herbal teas. It has been reported to have anti-microbial, anti-inflammatory, and anti-cancer activity. Non-small cell lung cancer (NSCLC) cell lines (A549, H441 and H520) and normal human bronchial epithelial cells (HBECs) were used to evaluate the cytotoxic effect of magnolol. We show that magnolol inhibited cellular proliferation, increased DNA fragmentation, and decreased mitochondrial membrane potential in all NSCLC cells, but had no cytotoxic effect on HBECs. Magnolol triggered the release of pro-apoptotic proteins: Bid, Bax and cytochrome c from mitochondria, but did not activate the caspase-3, -8, and -9, suggesting that magnolol induces apoptosis of NSCLC cell lines via a caspase-independent pathway. The caspase-independent pathway is mediated through the activation of nuclear translocation of apoptosis-inducing factor, endonuclease G and cleaved poly(ADP-ribose) polymerase, which played important roles in mediating cell death. Furthermore, magnolol inhibited PI3K/AKT and ERK1/2 activity, but up-regulated p38 and JNK activity in A549 cell lines. The results of this study provided a basis for understanding and developing magnolol as a novel treatment of NSCLC.
Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kao-hsiung, 80708, Taiwan.
Jong-Rung
JR
Tsai
Inn-Wen
IW
Chong
Yung-Hsiang
YH
Chen
Jhi-Jhu
JJ
Hwang
Wei-Hsian
WH
Yin
Hsiu-Lin
HL
Chen
Shah-Hwa
SH
Chou
Chien-Chih
CC
Chiu
Po-Len
PL
Liu
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects / Q000378:metabolism; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D020169:Caspases; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D001713:Biphenyl Compounds; D017705:Lignans; C005498:magnolol; D020169:Caspases