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Preclinical Development of Seriniquinones as Selective Dermcidin Modulators for the Treatment of Melanoma

Journal

MARINE DRUGS
Volume 20, Issue 5, Pages -

Publisher

MDPI
DOI: 10.3390/md20050301

Keywords

marine natural products; melanoma; seriniquinone; dermcidin; autophagy; apoptosis

Funding

  1. State of Sao Paulo Research Foundation
  2. FAPESP [2020/06613-8, 2015/17177-6]
  3. National Council for Scientific and Technological Development
  4. CNPq [443281/2019-0]
  5. US NIH [R37CA044848]

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Seriniquinone is a bioactive compound produced by a marine bacterium, showing significant anti-cancer activity against melanoma cells by targeting dermcidin (DCD). DCD is found to be a peptide associated with cancer cell survival, and seriniquinone exhibits enhanced potency against melanoma cell lines.
The bioactive natural product seriniquinone was discovered as a potential melanoma drug, which was produced by the as-yet-undescribed marine bacterium of the rare genus Serinicoccus. As part of a long-term research program aimed at the discovery of new agents for the treatment of cancer, seriniquinone revealed remarkable in vitro activity against a diversity of cancer cell lines in the US National Cancer Institute 60-cell line screening. Target deconvolution studies defined the seriniquinones as a new class of melanoma-selective agents that act in part by targeting dermcidin (DCD). The targeted DCD peptide has been recently examined and defined as a pro-survival peptide in cancer cells. While DCD was first isolated from human skin and thought to be only an antimicrobial peptide, currently DCD has been also identified as a peptide associated with the survival of cancer cells, through what is believed to be a disulfide-based conjugation with proteins that would normally induce apoptosis. However, the significantly enhanced potency of seriniquinone was of particular interest against the melanoma cell lines assessed in the NCI 60-cell line panel. This observed selectivity provided a driving force that resulted in a multidimensional program for the discovery of a usable drug with a new anticancer target and, therefore, a novel mode of action. Here, we provided an overview of the discovery and development efforts to date.

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