Dihydroaustrasulfone alcohol induces apoptosis in nasopharyngeal cancer cells by inducing reactive oxygen species-dependent inactivation of the PI3K/AKT pathway

• 영문명: Dihydroaustrasulfone alcohol induces apoptosis in nasopharyngeal cancer cells by inducing reactive oxygen species-dependent inactivation of the PI3K/AKT pathway
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Kok-Tong Tan Yu-Hung Shih Jiny Yin Gong Xiang Zhang Chiung-Yao Huan Jui-Hsin Su Jyh-Horng Sheu
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제27권 제4호, 383~398쪽, 전체 16쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2023.07.31

영문 초록

Dihydroaustrasulfone alcohol (DA), the synthetic precursor of a natural compound (austrasulfone) isolated from the coral species Cladiella australis, has shown cytotoxic effects against cancer cells. However, it is unknown whether DA has antitumor effects on nasopharyngeal carcinoma (NPC). In this study, we determined the antitumor effects of DA and investigated its mechanism of action on human NPC cells. The MTT assay was used to determine the cytotoxic effect of DA. Subsequently, apoptosis and reactive oxygen species (ROS) analyses were performed by using flow cytometry. Apoptotic and PI3K/AKT pathway-related protein expression was determined using Western blotting. We found that DA significantly reduced the viability of NPC-39 cells and determined that apoptosis was involved in DA-induced cell death. The activity of caspase-9, caspase-8, caspase-3, and PARP induced by DA suggested caspase-mediated apoptosis in DA-treated NPC-39 cells. Apoptosis-associated proteins (DR4, DR5, FAS) in extrinsic pathways were also elevated by DA. The enhanced expression of proapoptotic Bax and decreased expression of antiapoptotic BCL-2 suggested that DA mediated mitochondrial apoptosis. DA reduced the expression of pPI3K and p-AKT in NPC-39 cells. DA also reduced apoptosis after introducing an active AKT cDNA, indicating that DA could block the PI3K/AKT pathway from being activated. DA increased intracellular ROS, but N-acetylcysteine (NAC), a ROS scavenger, reduced DA-induced cytotoxicity. NAC also reversed the chances in pPI3K/AKT expression and reduced DA-induced apoptosis. These findings suggest that ROSmediates DA-induced apoptosis and PI3K/AKT signaling inactivation in human NPC cells.

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키워드

Apoptosis Dihydroaustrasulfone alcohol Nasopharyngeal carcinoma Proto-oncogene proteins c-akt Reactive oxygen species