Therapeutic potential of kakkatin derivatives against hepatocellular carcinoma

卡卡汀衍生物对肝细胞癌的治疗潜力

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Abstract

In this article, we commented on the work done by Jiang et al, where they synthesized a kakkatin derivative, 6-(hept-6-yn-1-yloxy)-3-(4-hydroxyphenyl)-7-methoxy-4H-chromen-4-one (HK), and investigated its antitumor activities and mechanism in gastric cancer MGC803 and hepatocellular carcinoma (HCC) SMMC-7721 cells. HK was evaluated for its antitumor activity as compared to kakkatin and cisplatin. This article focused on various risk factors of HCC, the mechanism of HCC progression and molecular targets of the kakkatin derivative, and limitations of available treatment options. HCC is a predominant form of primary liver cancer characterized by the accumulation of multiple gene modifications, overexpression of protooncogenes, altered immune microenvironment, and infiltration by immune cells. Puerariae flos (PF) has been used in traditional medicine in China, Korea, and Japan for lung clearing, spleen awakening, and relieving alcohol hangovers. PF exerts antitumor activity by inhibiting cancer cell proliferation, invasion, and migration. PF induces apoptosis in alcoholic HCC via the estrogen-receptor 1-extracellular signal-regulated kinases 1/2 signaling pathway. Kakkatin isolated from PF is known as a hepatoprotective bioflavonoid. The kakkatin derivative, HK, exhibited anticancer activity against HCC cell lines by inhibiting cell proliferation and upregulating nuclear factor kappa B subunit 1 and phosphodiesterase 3B. However, further preclinical and clinical studies are required to establish its therapeutic potential against HCC.

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