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At present, melanoma is a common malignant tumor with the highest mortality rate of all types of skin cancer. Although the first option for treating melanoma is with chemicals, the effects are unsatisfactory and include poor medication response and high resistance. Therefore, developing new medicines or a novel combination approach would be a significant breakthrough. Here, we present cinnamaldehyde (CA) as a potential candidate, which exerted an antitumor effect in melanoma cell lines. Chemical biology methods of target fishing, molecular imaging, and live cell tracing by an alkynyl-CA probe revealed that the α-enolase (ENO1) protein was the target of CA. The covalent binding of CA with ENO1 changed the stability of the ENO1 protein and affected the glycolytic activity. Furthermore, our results demonstrated that dacarbazine (DTIC) showed a high promoting effect with CA for antimelanoma both in vivo and in vitro. The combination improved the DTIC cell cycle arrest in the S phase and markedly impacted melanoma growth. As a covalent inhibitor of ENO1, CA combined with DTIC may be beneficial in patients with drug resistance in antimelanoma therapy.

Cinnamaldehyde Enhances Antimelanoma Activity through Covalently Binding ENO1 and Exhibits a Promoting Effect with Dacarbazine