Magnolol, a natural compound, induces apoptosis of SGC-7901 human gastric adenocarcinoma cells via the mitochondrial and PI3K/Akt signaling pathways

Abstract

Abstract. Gastric cancer is the fourth most commonly diagnosed cancer with the second highest mortality rate worldwide. Surgery, chemotherapy and radiation therapy are generally used for the treatment of stomach cancer but only limited clinical response is shown by these therapies and still no effectual therapy for advanced gastric adenocarcinoma patients is available. Therefore, there is a need to identify other therapeutic agents against this life-threatening disease. Plants are considered as one of the most important sources for the development of anticancer drugs. Magnolol, a natural compound possesses anticancer properties. However, effects of Magnolol on human gastric cancer remain unexplored. The effects of Magnolol on the viability of SGC-7901 cells were determined by the MTT assay. Apoptosis, mitochondrial membrane potential and cell cycle were evaluated by flow cytometry. Protein expression of Bcl-2, Bax, caspase-3 and PI3K/Akt was analysed by Western blotting. Magnolol induced morphological changes in SGC-7901 cells and its cytotoxic effects were linked with DNA damage, apoptosis and S-phase arrest in a dose-dependent manner. Magnolol triggered the mitochondrial-mediated apoptosis pathway as shown by an increased ratio of Bax/Bcl-2, dissipation of mitochondrial membrane potential (ΔΨm), and sequential activation of caspase-3 and inhibition of PI3K/Akt. Additionally, Magnolol induced autophagy in SGC-7901 cells at high concentration but was not involved in cell death. Magnolol-induced apoptosis of SGC-7901 cells involves mitochondria and PI3K/ Akt-dependent pathways. These findings provide evidence that Magnolol is a promising natural compound for the treatment of gastric cancer and may represent a candidate for in vivo studies of monotherapies or combination antitumor therapies. IntroductionGastric cancer is the second most common cause of cancerrelated death worldwide and approximately 800,000 people die each year of this malignancy. So far it is the fourth most frequently diagnosed cancer as each year more than one million patients are annually diagnosed with gastric cancer (1,2). The incidence of stomach cancer varies geographically, with a much higher prevalence in Eastern countries than in the Western ones (3). In 2005, the incidence of gastric cancer (0.3 million deaths and 0.4 million new cases) ranked third among the most common cancers in China (4). Although surgery remains the gold standard for the treatment of stomach cancer but the limitations is that it is diagnosed at an advanced stage. The 5-year survival rate of patients with advanced gastric cancer for surgical treatment is less than 40%. The effectiveness of chemotherapy and/or radiation therapy, in addition to surgery, has been actively studied over the last few decades. Unfortunately, only a little clinical response is generally shown by chemotherapy or radiation therapy and survival rate is also very poor (5). There is no effective therapy for patients with advanced gastric adenocarcinoma. Therefore, to identify new therapeutic ag...

Magnolol-Induced Apoptosis in HCT-116 Colon Cancer Cells Is Associated with the AMP-Activated Protein Kinase Signaling Pathway

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