Publication: Inhibition of Topoisomerase IIα and induction of apoptosis in gastric cancer cells by 19-triisopropyl andrographolide
Issued Date
2017-10-01
Resource Type
ISSN
2476762X
15137368
15137368
Other identifier(s)
2-s2.0-85031910005
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Asian Pacific Journal of Cancer Prevention. Vol.18, No.10 (2017), 2845-2851
Suggested Citation
Adeep Monger, Nittaya Boonmuen, Kanoknetr Suksen, Rungnapha Saeeng, Teerapich Kasemsuk, Pawinee Piyachaturawat, Witchuda Saengsawang, Arthit Chairoungdua Inhibition of Topoisomerase IIα and induction of apoptosis in gastric cancer cells by 19-triisopropyl andrographolide. Asian Pacific Journal of Cancer Prevention. Vol.18, No.10 (2017), 2845-2851. doi:10.22034/APJCP.2017.18.10.2845 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/41769
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Inhibition of Topoisomerase IIα and induction of apoptosis in gastric cancer cells by 19-triisopropyl andrographolide
Other Contributor(s)
Abstract
Gastric cancer is the most common cancer in Eastern Asia. Increasing chemoresistance and general systemic toxicities have complicated the current chemotherapy leading to an urgent need of more effective agents. The present study reported a potent DNA topoisomerase IIa inhibitory activity of an andrographolide analogue (19-triisopropyl andrographolide, analogue-6) in gastric cancer cells; MKN-45, and AGS cells. The analogue was potently cytotoxic to both gastric cancer cell lines with the half maximal inhibitory concentration (IC50values) of 6.3±0.7 μM, and 1.7±0.05 μM at 48 h for MKN-45, and AGS cells, respectively. It was more potent than the parent andrographolide and the clinically used, etoposide with the IC50values of > 50 μM in MKN-45 and 11.3±2.9 μM in AGS cells for andrographolide and 28.5±4.4 μM in MKN-45 and 4.08±0.5 μM in AGS cells for etoposide. Analogue-6 at 2 μM significantly inhibited DNA topoisomerase IIa enzyme in AGS cells, induced DNA damage, activated cleaved PARP-1, and Caspase3 leading to late cellular apoptosis. Interestingly, the expression of tumor suppressor p53 was not activated. These results show the importance of 19-triisopropyl-andrographolide in its emerging selectivity to primary target on topoisomerase IIa enzyme, inducing DNA damage and apoptosis by p53- independent mechanism. Thereby, the results provide insights of the potential of 19-triisopropyl andrographolide as an anticancer agent for gastric cancer. The chemical transformation of andrographolide is a promising strategy in drug discovery of a novel class of anticancer drugs from bioactive natural products.