Ilimaquinone Induces Apoptosis and Autophagy in Human Oral Squamous Cell Carcinoma Cells

Biomedicines

Chang-Fang Chiu¹  Ming-Cheng Shih²  Wei-Ting Huang²  Jing-Lan Hu³  Jing-Ru Weng³  Cheng-Wen Lin⁴  Yu-Ting Huang⁵  Wei-Yu Lin⁶  Li-Yuan Bai⁷  Jui-Hsin Su⁸ 

[1] College of Medicine, China Medical University, Taichung 40402, Taiwan;Department of Biological Science & Technology, I-Shou University, Kaohsiung 82445, Taiwan;Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan;Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 40402, Taiwan;Department of Nutrition, I-Shou University, Kaohsiung 82445, Taiwan;Department of Pharmacy, Kinmen Hospital, Kinmen 89142, Taiwan;Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung 40447, Taiwan;National Museum of Marine Biology and Aquarium, Pingtung 94450, Taiwan;

关键词: ilimaquinone;    OSCC;    autophagy;    apoptosis;    p53;   

DOI  :  10.3390/biomedicines8090296

来源: DOAJ

【 摘 要 】

In this study, the anti-tumor activity of ilimaquinone (IQ), a sesquiterpene quinone isolated from marine sponge Halichondria sp., in oral squamous cell carcinoma (OSCC) cells, was investigated. IQ suppressed the viability of the OSCC cell lines SCC4 and SCC2095 with IC₅₀ values of 7.5 and 8.5 mM, respectively. Flow cytometric analysis demonstrated that IQ induced caspase-dependent apoptosis in SCC4 cells and modulated the expression of several cell growth-related gene products, including Akt, p38, Mcl-1, and p53. Notably, p53 knockdown caused higher resistance to IQ’s anti-tumor activity. In addition, IQ increased reactive oxygen species generation, which was partially reversed by the addition of antioxidants. Furthermore, it triggered autophagy, as evidenced by acidic organelle formation and LC3B-II and Atg5 expression in SCC4 cells. Pretreatment with the autophagy inhibitor 3-methyladenine or chloroquine partially decreased IQ-induced apoptosis, suggesting that IQ induced protective autophagy. In summary, IQ has potential to be used in OSCC therapy.

【 授权许可】

Unknown