Unknown

Dataset Information

0

MHY2245, a Sirtuin Inhibitor, Induces Cell Cycle Arrest and Apoptosis in HCT116 Human Colorectal Cancer Cells.


ABSTRACT: Sirtuins (SIRTs), which are nicotinamide adenine dinucleotide-dependent class III histone deacetylases, regulate cell division, survival, and senescence. Although sirtinol, a synthetic SIRT inhibitor, is known to exhibit antitumor effects, its mechanism of action is not well understood. Therefore, we aimed to assess the anticancer effects and underlying mechanism of MHY2245, a derivative of sirtinol, in HCT116 human colorectal cancer cells in vitro. Treatment with MHY2245 decreased SIRT1 activity and caused DNA damage, leading to the upregulation of p53 acetylation, and increased levels of p53, phosphorylation of H2A histone family member X, ataxia telangiectasia and Rad3-related kinase, checkpoint kinase 1 (Chk1), and Chk2. The level of the breast cancer type 1 susceptibility protein was also found to decrease. MHY2245 induced G2/M phase cell cycle arrest via the downregulation of cyclin B1, cell division cycle protein 2 (Cdc2), and Cdc25c. Further, MHY2245 induced HCT116 cell death via apoptosis, which was accompanied by internucleosomal DNA fragmentation, decreased B-cell lymphoma 2 (Bcl-2) levels, increased Bcl-2-asscociated X protein levels, cleavage of poly(ADP-ribose) polymerase, and activation of caspases -3, -8, and -9. Overall, MHY2245 induces cell cycle arrest, triggers apoptosis through caspase activation, and exhibits DNA damage response-associated anticancer effects.

SUBMITTER: Kang YJ 

PROVIDER: S-EPMC8835956 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications

MHY2245, a Sirtuin Inhibitor, Induces Cell Cycle Arrest and Apoptosis in HCT116 Human Colorectal Cancer Cells.

Kang Yong Jung YJ   Jang Jung Yoon JY   Kwon Young Hoon YH   Lee Jun Ho JH   Lee Sanggwon S   Park Yujin Y   Jung Young-Suk YS   Im Eunok E   Moon Hyung Ryong HR   Chung Hae Young HY   Kim Nam Deuk ND  

International journal of molecular sciences 20220129 3


Sirtuins (SIRTs), which are nicotinamide adenine dinucleotide-dependent class III histone deacetylases, regulate cell division, survival, and senescence. Although sirtinol, a synthetic SIRT inhibitor, is known to exhibit antitumor effects, its mechanism of action is not well understood. Therefore, we aimed to assess the anticancer effects and underlying mechanism of MHY2245, a derivative of sirtinol, in HCT116 human colorectal cancer cells in vitro. Treatment with MHY2245 decreased SIRT1 activit  ...[more]

Similar Datasets

| S-EPMC6521147 | biostudies-literature
| S-EPMC9966721 | biostudies-literature
| S-EPMC2883702 | biostudies-other
| S-EPMC6521404 | biostudies-literature
| S-EPMC5787485 | biostudies-literature
| S-EPMC9515697 | biostudies-literature
| S-EPMC7987731 | biostudies-literature
| S-EPMC5085043 | biostudies-literature
| S-EPMC3759946 | biostudies-literature
| S-EPMC4516515 | biostudies-literature