Gastric cancer has severe morbidity and mortality rates and is the fifth most common cancer globally. This cancer is known to metastasize aggressively, making it very challenging to control. Research has shown histone deacetylase 6 (HDAC6) being related to this specific cancer and has therefore become a target in searching for an effective treatment.
Carbenoxolone disodium has been identified through the use of high-throughput screening as an inhibitor of HDAC6. Carbenoxolone disodium is an active metabolite of glycyrrhizic acid, a natural compound known for its anti-inflammatory properties. A recent study at Zhengzhou University tested the effectiveness of carbenoxolone in cell culture studies and in a mouse model.
In the cell culture studies, normal gastric cells were tested alongside two types of gastric cancer cells. The test results showed that carbenoxolone could block the growth of the cancer cells without showing toxicity to the normal cells. This indicates that this chemical may be a relatively safe agent. The tests also showed that carbenoxolone blocked the wound healing of the cancer cells, inhibiting the migration capacity. And finally, the process of epithelial-mesenchymal transition was reversed after the treatment. Epithelial-mesenchymal transition is an important process allowing cancer cells to increase their mobility.
In the animal study, nude mice and the gastric cancer cells were used to establish a lung cancer metastasis model. Afterwards, oral treatment with carbenoxolone was administered. The results of this experiment showed that carbenoxolone treatment significantly inhibited the lung metastasis.
This study confirms carbenoxolone disodium to be a selective and potent inhibitor for HDAC6 in gastric cancer cells. This is a good lead for development of an anti-metastasis drug against gastric cancer.
Song Z, Zhao C, Yan J, et al. Carbenoxolone disodium suppresses the migration of gastric cancer by targeting HDAC6. Future Med Chem. 2023 Feb;15(4):333-344. doi: 10.4155/fmc-2022-0246. PMID: 36946221