Carbenoxolone Disodium Suppresses the Migration of Gastric Cancer By Targeting HDAC6

Abstract

Aim: Because of the severe morbidity and mortality of gastric cancer, discovering new candidate drugs has been an urgent issue. The close association between histone deacetylase 6 (HDAC6) and gastric cancer makes the development of HDAC6-targeted anti-gastric cancer drugs a viable idea. Methods & results: Carbenoxolone disodium was identified as a novel HDAC6 inhibitor. Cellular thermal shift assay, surface plasmon resonance assay and molecular docking confirmed its binding ability to HDAC6. Cell viability, wound healing and transwell assays as well as animal studies have demonstrated that carbenoxolone disodium could block the proliferation and migration of gastric cancer cells MGC-803 in vitro and in vivo. Conclusion: This is the first report to indicate that carbenoxolone disodium could be an HDAC6 inhibitor with potential for treatment of gastric cancer.

Development of First-in-Class Dual Sirt2/HDAC6 Inhibitors as Molecular Tools for Dual Inhibition of Tubulin Deacetylation

“…All selected cell lines were isolated from tumor types that were already investigated regarding the effects of Sirt2 and HDAC6 inhibition, respectively. 9 , 47 , 55 − 58 Whereas most of the tested dual Sirt2/HDAC6 inhibitors showed no effects on cell viability, compound 33 reduced the viability of all tested cancer cell lines. These results are consistent with the data from our cell-based studies investigating α-tubulin acetylation ( Figure 7 ), where we also detected the strongest effects for this dual Sirt2/HDAC6 inhibitor.…”

“…Thus, we tested our dual Sirt2/HDAC6 inhibitors against a panel of solid cancer cell lines of different chemosensitivity and tissue origin, including HGC27 gastric carcinoma cells, W1 ovarian cancer cells, MCF-7 breast cancer cells, and PC-3M-luc prostate cancer cells (Table ). All selected cell lines were isolated from tumor types that were already investigated regarding the effects of Sirt2 and HDAC6 inhibition, respectively. ,,− Whereas most of the tested dual Sirt2/HDAC6 inhibitors showed no effects on cell viability, compound 33 reduced the viability of all tested cancer cell lines. These results are consistent with the data from our cell-based studies investigating α-tubulin acetylation (Figure ), where we also detected the strongest effects for this dual Sirt2/HDAC6 inhibitor.…”

“…1 H NMR a (400 MHz, DMSO-d 6 , δ [ppm]): 11.20, 11.17 13 C NMR a (101 MHz, DMSO-d 6 , δ [ppm]): 172.2, 172.1 q (−CH 2 -N(C 4 H 9 )-CO-C 4 H 9 ), 164.1, 163.9 q (−CO-NH-OH), 141.9, 141.5 q (N-hydroxybenzamide C-4), 131.6, 131.4 q (Nhydroxybenzamide C-1), 127. (58). 65 Ethyl 4-(aminomethyl)benzoate (37, 206 mg, 1.212 mmol, 1 equiv) and DIPEA (235 mg, 316.5 μL, 1.818 mmol, 1.5 equiv) were dissolved in 7 mL of dichloromethane and cooled in an ice bath to 0 °C.…”