The application of natural compounds in uveal melanoma drug discovery

J Pharm Pharmacol. 2022 May 20;74(5):660-680. doi: 10.1093/jpp/rgac009.

Abstract

Objectives: Uveal melanoma (UM) is the most common primary intraocular tumour in adults. UM has a poor overall prognosis and ~50% of patients progress to metastatic disease that has a median survival of 5.2 months. There are currently no proven pharmacological treatments for primary or metastatic UM. Research efforts continue to seek new agents. Many natural compounds have shown promising anti-UM activity in in-vitro and/or in-vivo studies. This review summarises the current findings for natural compounds that may be potentially useful in treating UM.

Key findings: Literature suggests that natural compounds, such as pristimerin, picropodophyllin, oridonin, zeaxanthin, withaferin and FR-900359, may be promising candidate compounds to treat UM. Most of these compounds have demonstrated satisfactory efficacy in inhibiting in-vitro UM cell growth.

Summary: The evidence regarding the anti-UM effects of natural compounds is mainly limited to in-vitro studies; to date, only a small number of these agents have been evaluated in vivo. The molecular mechanisms underpinning the anti-UM properties of these compounds remain largely undefined. Further studies are required to evaluate the in-vivo anticancer activity, appropriate dosage regimen and safety of natural compounds that could be developed for use in UM.

Keywords: drug therapy; natural compounds; picropodophyllin; pristimerin; uveal melanoma; zeaxanthin.

Publication types

  • Review

MeSH terms

  • Adult
  • Cell Line, Tumor
  • Drug Discovery
  • Humans
  • Melanoma
  • Pentacyclic Triterpenes
  • Uveal Neoplasms* / drug therapy
  • Uveal Neoplasms* / pathology

Substances

  • Pentacyclic Triterpenes
  • celastrol methyl ester

Supplementary concepts

  • Uveal melanoma