Magnolol-lnduced H460 cells deathvia autophagy but not apoptosis
- 217 Downloads
We have reported that the protective effect of Magnolol on TBHP-induced injury in human non-small lung cancer H460 cells is partiallyvia a p53 dependent mechanism. In this study, we found that Magnolol displayed a stimulatory effect at low concentrations (≤20 μM) whilst inhibitory effect at high concentrations (≥40 μM) 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 notvia apoptotic pathway. Furthermore, accompanied by the occurrence of autophagy, the expression of phospho-Akt was down-regulated but PTEN signif-icantly 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 util-ity of its induction as a new cancer treatment modality.
Key wordsMagnolol H460 Autophagy Apoptosis
Unable to display preview. Download preview PDF.
- Arico, S., Petiot, A., Bauvy, C., Dubbelhuis, P. F., Meijer, A. J., Codogno, P., and Ogier-denis, E., The tumor suppressor PTEN positively regulates macroautophagy by inhibiting the phosphatidylinositol 3-kinase/protein kinase B pathway.J. Biol. Chem, 276, 35243–35246 (2001).PubMedCrossRefGoogle Scholar
- Bursch, W., Ellinger, A., Kienzl, H., Torok, L., Pandey, S., Sikorska, M., Walker, R., and Hermann, R. S., Active cell death induced by the anti-estrogens tamoxifen and ICI 164 384 in human mammary carcinoma cells (MCF-7) in culture: the role of autophagy.Carcinogenesis, 17, 1595–607 (1996).PubMedCrossRefGoogle Scholar
- Li, H., Gao, J.-M., Ying, X., Wang, S., and Li, J., Protective Effect of Magnolol on TBHP-lnduced Injury in H460 Cells Partially via a p53 Dependent Mechanism (inpress).Google Scholar
- Iwamaru, A., Kondo, Y., Iwado, E., Aoki, H., Fujiwara, K., Yoko-yama, T., Mills, G. B., and Kondo, S., Silencing mammalian target of rapamycin signaling by small interfering RNA enhances rapamycin-induced autophagy in malignant glioma cells.Oncogene, 26, 1840–1851 (2007).PubMedCrossRefGoogle Scholar
- Kishimoto, H., Ohteki, T., Yajima, N., Kawahara, K., Natsui, M., Kawarasaki, S., Hamada, K., Horie, Y, Kubo, Y, Arase, S., Taniguchi, M., Vanhaesebroeck, B., Mak, T. W., Nakano, T., Koyasu, S., Sasaki, T., and Suzuki, A., The Pten/PI3K pathway governs the homeostasis of Valpha14iNKT cells.Blood, 109, 3316–3324 (2007).PubMedCrossRefGoogle Scholar
- Lee, J. O., Yang, H., Georgescu, M. M., Di Cristofano, A., Maehama, T., Shi, Y., Dixon, J. E., Pandolfi, P., and Pavletich, N. P., Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association.Cell, 99, 323–334 (1999).PubMedCrossRefGoogle Scholar