Topical 3-bromopyruvate is a novel targeted therapy for melanoma in a preclinical model

Publication date: Available online 30 August 2018

Source: Journal of Dermatological Science

Author(s): Masayuki Yamada, Masami Kagaya, Natsuko Noguchi, Shigeharu Ueki, Naoko Hasunuma, Shin-Ichi Osada, Motomu Manabe

Abstract

Background

Targeting cancer metabolism is a promising strategy in improving cancer treatment.

Objective

To introduce a targeted therapy with topical 3-bromopyruvate (3BP), aglycolytic inhibitor, into the clinic in the near future.

Method

We investigated the anti-tumor efficacy of 3BP on melanoma cells in vitro and in a preclinical model.

Results

Our cell-based study demonstrated that 3BP showed cytotoxicity for melanoma cells under anchorage-dependent or independent cell growth via a reactive oxygen species-mediated and caspase-independent cell death pathway. Moreover, 3BP inhibited both self-renewal potential and growth of slow-cycling phenotype in melanoma cells. Remarkably, the preclinical mouse xenograft model shed light on topical application of 3BP, showing significant anti-tumor effects with no apparent toxicity in surrounding normal tissues.Conclusion: We have now proposed that a targeted therapy with topical 3BP is an innovative strategy for adjuvant chemotherapy of technically or medically unresectable melanoma and possibly other skin cancers.

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