A new synthetic 2′-hydroxy-2,4,6-trimethoxy-5′,6′-naphthochalcone induces G2/M cell cycle arrest and apoptosis by disrupting the microtubular network of human colon cancer cells

• HMNC-74 is a novel methoxylated benzochalcone derivative.
• HMNC-74 is more cytotoxic to cancer cells than non-cancerous cells in culture.
• HMNC-74 induces G2/M cell cycle arrest through the inhibition of tubulin polymerization.
• HMNC-74 activates p53 and caspase-2, leading to apoptosis.
• HMNC-74 may be a promising antimitotic agent.

Methoxylated chalcones exert antitumor activities. In the present study, we characterized the cytotoxicity of methylated chalcone derivatives against human colon cancer cells. We synthesized a group of methoxychalcones and explored the molecular mechanisms underlying inhibition of tumor growth by these materials. A new synthetic methoxychalcone, 2′-hydroxy-2,4,6-trimethoxy-5′,6′-naphthochalcone (named HMNC-74), most effectively inhibited the clonogenicity of SW620 colon cancer cells. Mechanistically, HMNC-74 triggered cell cycle arrest at G2/M phase, followed by an increase in apoptotic cell death. Our results indicate that the cytotoxicity of the novel compound HMNC-74 involves the disruption of microtubular networks.