Tetracaine hydrochloride induces cell cycle arrest in melanoma by downregulating hnRNPA1

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Local anesthetics, including tetracaine, show potential antitumor effects in various cancers.
• The precise molecular mechanisms behind tetracaine's anticancer activity, particularly in melanoma, are not fully understood.

Purpose of the Study:

• To investigate the molecular mechanisms of tetracaine hydrochloride's antitumor effects in melanoma.
• To elucidate the role of heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) in tetracaine's action on melanoma cells.

Main Methods:

• In vitro studies using melanoma cell lines treated with tetracaine hydrochloride.
• Analysis of hnRNPA1 localization, protein stability, and its interaction with cell cycle regulators.
• In vivo studies using melanoma homograft models in mice.

Main Results:

• Tetracaine hydrochloride inhibited melanoma cell growth and induced G0/G1 cell cycle arrest.
• Tetracaine treatment caused hnRNPA1 translocation and reduced its protein stability, impacting ubiquitination and neddylation.
• Elevated hnRNPA1 levels were found to upregulate cyclin D1, promoting cell cycle progression.
• Overexpression of hnRNPA1 attenuated tetracaine's inhibitory effects on melanoma cell growth and cell cycle arrest.
• In vivo experiments confirmed tetracaine's suppression of melanoma growth, with hnRNPA1 overexpression mitigating this effect.

Conclusions:

• Tetracaine hydrochloride demonstrates potent in vitro and in vivo antitumor activity against melanoma.
• The mechanism involves inducing cell cycle arrest through the downregulation of hnRNPA1.
• Targeting hnRNPA1 could be a therapeutic strategy in combination with tetracaine for melanoma treatment.