Magnolol-induced H460 cells death via autophagy but not apoptosis.
We have reported that the protective effect of Magnolol on TBHP-induced injury in human nonsmall lung cancer H460 cells is partially via a p53 dependent mechanism. In this study, we found that Magnolol displayed a stimulatory effect at low concentrations (< or = 20 microM) whilst inhibitory effect at high concentrations (> or = 40 microM) in H460 cells. To investigate the mechanism of inducing the biphasic effect in H460 cells with Magnolol, we showed that Magnolol stimulated DNA synthesis at low concentrations and displayed an inhibition effect at high concentrations in H460 cells. More importantly, the inhibition of DNA synthesis was accompanied by the S phase cell cycle arrest and the appearance of intense intracytoplasmic vacuoles. These vacuoles can be labeled by autophagic marker monodansylcadaverin (MDC), 3-methyladenine (3-MA), an inhibitor of autophagy, was able to inhibit the occurrence of autophagy. The results of the LDH activity assay and TUNEL assay also showed that Magnolol at high concentrations inhibiting H460 cell growth was not via apoptotic pathway. Furthermore, accompanied by the occurrence of autophagy, the expression of phospho-Akt was down-regulated but PTEN significantly was up-regulated. In conclusion, Magnolol induces H460 cells death by autophagy but not apoptotic pathway. Blockade of PI3K/PTEN/Akt pathway is maybe related to Magnolol-induced autophagy. Autophagic cells death induction by Magnolol underlines the potential utility of its induction as a new cancer treatment modality.
Li
Hai-Bo
HB
School of Basic Medical Sciences, Liaoning University of TCM, 79 Chongshan East Road, Shenyang 110032, China.
Yi
Xin
X
Gao
Jian-Mei
JM
Ying
Xi-Xiang
XX
Guan
Hong-Quan
HQ
Li
Jian-Chun
JC
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology
D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D017705:Lignans; C005498:magnolol; D004247:DNA; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human