Mechanisms for the magnolol‐induced cell death of CGTH W‐2 thyroid carcinoma cells

Abstract

Magnolol, a substance purified from the bark of Magnolia officialis, inhibits cell proliferation and induces apoptosis in a variety of cancer cells. The aim of this study was to study the effects of magnolol on CGTH W-2 thyroid carcinoma cells. After 24 h treatment with 80 microM magnolol in serum-containing medium, about 50% of the cells exhibited apoptotic features and 20% necrotic features. Cytochrome-c staining was diffused in the cytoplasm of the apoptotic cells, but restricted to the mitochondria in control cells. Western blot analyses showed an increase in levels of activated caspases (caspase-3 and -7) and of cleaved poly (ADP-ribose) polymerase (PARP) by magnolol. Concomitantly, immunostaining for apoptosis inducing factor (AIF) showed a time-dependent translocation from the mitochondria to the nucleus. Inhibition of either PARP or caspase activity blocked magnolol-induced apoptosis, supporting the involvement of the caspases and PARP. In addition, magnolol activated phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and inactivated Akt by decreasing levels of phosphorylated PTEN and phosphorylated Akt. These data suggest that magnolol promoted apoptosis probably by alleviating the inhibitory effect of Akt on caspase 9. Furthermore, inhibition of PARP activity, but not of caspase activity, completely prevented magnolol-induced necrosis, suggesting the notion that it might be caused by depletion of intracellular ATP levels due to PARP activation. These results show that magnolol initiates apoptosis via the cytochrome-c/caspase 3/PARP/AIF and PTEN/Akt/caspase 9/PARP pathways and necrosis via PARP activation.

2-O-Methylmagnolol Induces Apoptosis and Inhibits IL-6/STAT3 Signaling in Oral Squamous Cell Carcinoma

“…Magnolol triggers the release of Bid, Bax and cytochrome c from mitochondria, and induces apoptosis via a caspase-independent pathway in non-small cell lung cancer cells [7]. Induction of apoptosis by magnolol has been reported to mediate through caspaseindependent pathway and G2/M phase arrest in human breast cancer cells [9], and through cytochrome c/caspase 3/PARP and PTEN/Akt pathways in thyroid carcinoma cells [28]. The regulatory pathways of MM1-induced apoptosis in different cancers, on the other hand, are poorly understood at present.…”

Effects of Obovatol on GSH Depleted Glia-Mediated Neurotoxicity and Oxidative Damage

“…Their efficacy is higher, and side effects are significantly lower than with synthetic compounds (Baker et al 2007). Obovatol (5-prop-2-enyl-3-(4-prop-2-enylphenoxy)benzene-1,2-diol) (OBO), a newly found compound isolated from extracts of Magnolia obovata, is supposed to have great therapeutic potential as suggested by antitumor, anti-depressant, and antiinflammatory activity (Huang et al 2007;Xu et al 2008;Choi et al 2007;Lee et al 2008a). However, the mechanism underlying its biological action is not known.…”

Anticancer potential of magnolol for lung cancer treatment

“…Recently, a number of studies have drawn attention to the anticancer properties of magnolol. Previous studies have revealed that magnolol inhibits the proliferation and induces the apoptosis of several cancer cell lines including colon cancer, HepG2 hepatoma, leukemia, fibrosarcoma, melanoma, squamous carcinoma, and thyroid carcinoma cells (Lin et al, 2001(Lin et al, , 2002Yang et al, 2003;Zhong et al, 2003;Huang et al, 2007). However, the potential anticancer properties of magnolol against NSCLC are not well-known.…”