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

Area of Science:

• Oncology
• Biochemistry
• Chemical Biology

Background:

• Melanoma is a deadly skin cancer with limited treatment options due to poor response and resistance.
• Current chemotherapy for melanoma often yields unsatisfactory outcomes.
• Novel therapeutic strategies and drug combinations are crucial for improving melanoma treatment.

Purpose of the Study:

• To identify the molecular target of cinnamaldehyde (CA) in melanoma.
• To evaluate the antitumor effects of CA alone and in combination with dacarbazine (DTIC) against melanoma.
• To explore the potential of CA-DTIC combination therapy for drug-resistant melanoma.

Main Methods:

• Target fishing, molecular imaging, and alkynyl-CA probe for identifying CA's protein target.
• Assessing the impact of CA on ENO1 protein stability and glycolytic activity.
• In vitro and in vivo studies to evaluate the combined efficacy of CA and DTIC against melanoma.

Main Results:

• Cinnamaldehyde (CA) was identified as a covalent inhibitor of alpha-enolase (ENO1).
• CA binding to ENO1 altered protein stability and affected cellular glycolytic activity.
• The combination of CA and dacarbazine (DTIC) demonstrated synergistic antimelanoma effects in vitro and in vivo.
• The CA-DTIC combination enhanced DTIC-induced cell cycle arrest at the S phase, significantly inhibiting melanoma growth.

Conclusions:

• Cinnamaldehyde (CA) is a novel covalent inhibitor of alpha-enolase (ENO1) with antitumor activity in melanoma.
• The combination of CA and dacarbazine (DTIC) exhibits enhanced efficacy against melanoma, including drug-resistant forms.
• CA, as an ENO1 inhibitor, holds promise for improving melanoma treatment outcomes, especially in combination therapy.