Anti-Cancer Effects of Combination Treatment of β-hydroxybutyrate and cisplatin in Colon cancer cells

다국어 초록 (Multilingual Abstract)

Anti-Cancer Effects of Combination Treatment of β-hydroxybutyrate and cisplatin in Colon cancer cells by Jiwon Jang Master of Biomedical Science Graduate School of Kyung Hee University Advised by Dr. Insug Kang This study investigated the combined effects of β-hydroxybutyrate (BHB) and cisplatin on colorectal cancer (CRC) cells. BHB significantly increased cisplatin-induced cell apoptosis in CRC cells. The combination of BHB and cisplatin induced the conversion of autophagy-related protein LC3-II and the degradation of p62. Inhibition by autophagy inhibitors, bafilomycin A1, and 3-methyladenine, decreased cell apoptosis, LC3-II conversion, and p62 degradation caused by combined treatment. Furthermore, the combination of BHB and cisplatin activated MAPKs, leading to increased levels of p-JNK and p-38, ultimately inducing cell apoptosis. Additionally, the antioxidant NAC reduced cell apoptosis induced by combined treatment. The combination of BHB and cisplatin induced histone H3 acetylation and decreased the expression of HDAC3, 4, and 10. Lastly, combined treatment enhanced the inhibitory effect of cisplatin on cell migration. In conclusion, these results demonstrate that the combination of BHB and cisplatin induces cell apoptosis in CRC cells through autophagy, MAPKs, and ROS, revealing its anticancer effects. Key words β-hydroxybutyrate, cisplatin, autophagy, MAPKs, ROS

목차 (Table of Contents)

• Abstract ⅲ
• 1. Introduction · 1
• 2. Materials and Methods · 2
• 3. Results · 4
• 4. Discussion · 22
• 5. SUMMARY 24
• 6. References · 25
• Figure Contents
• Figure 1.
• Effects of combination treatment of BHB and cisplatin on cell viability in CRC cells 5
• Figure 2.
• Effect of combination treatment of BHB and cisplatin on apoptosis of RKO cells · 6
• Figure 3.
• Combination treatment of BHB and cisplatin induces cell death in caspase dependent manner 8
• Figure 4.
• Effect of combination treatment of BHB and cisplatin on autophagy in CRC cells 10
• Figure 5.
• Effects of combination treatment of BHB and cisplatin on the activation of MAPKs in CRC
• cells 13
• Figure 6.
• Effects of combination treatment of BHB and cisplatin on ROS accumulation in CRC cells 16
• Figure 7.
• Effects of combination treatment of BHB and cisplatin on histone H3 acetylation and HDAC
• expression in CRC cells 18
• Figure 8.
• Effect of combination treatment of BHB and cisplatin on migration in CRC cells 20