Hibiscus sabdariffa leaf polyphenolic extract induces human melanoma cell death, apoptosis, and autophagy

J Food Sci. 2015 Mar;80(3):H649-58. doi: 10.1111/1750-3841.12790. Epub 2015 Feb 17.

Abstract

Melanoma is the least common but most fatal form of skin cancer. Previous studies have indicated that an aqueous extract of Hibiscus sabdariffa leaves possess hypoglycemic, hypolipidemic, and antioxidant effects. In this study, we want to investigate the anticancer activity of Hibiscus leaf polyphenolic (HLP) extract in melanoma cells. First, HLP was exhibited to be rich in epicatechin gallate (ECG) and other polyphenols. Apoptotic and autophagic activities of HLP and ECG were further evaluated by DAPI stain, cell-cycle analysis, and acidic vascular organelle (AVO) stain. Our results revealed that both HLP and ECG induced the caspases cleavages, Bcl-2 family proteins regulation, and Fas/FasL activation in A375 cells. In addition, we also revealed that the cells presented AVO-positive after HLP treatments. HLP could increase the expressions of autophagy-related proteins autophagy-related gene 5 (ATG5), Beclin1, and light chain 3-II (LC3-II), and induce autophagic cell death in A375 cells. These data indicated that the anticancer effect of HLP, partly contributed by ECG, in A375 cells. HLP potentially could be developed as an antimelanoma agent.

Keywords: Hibiscus sabdariffa leaf; apoptosis; autophagy; epicatechin gallate; melanoma; polyphenol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins / metabolism
  • Autophagy / drug effects
  • Autophagy-Related Protein 5
  • Beclin-1
  • Caspases / metabolism
  • Catechin / analogs & derivatives
  • Catechin / pharmacology
  • Catechin / therapeutic use
  • Cell Line, Tumor
  • Hibiscus / chemistry*
  • Humans
  • Melanoma / drug therapy*
  • Melanoma / metabolism
  • Membrane Proteins / metabolism
  • Microtubule-Associated Proteins / metabolism
  • Phytotherapy*
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Plant Leaves / chemistry
  • Polyphenols / pharmacology
  • Polyphenols / therapeutic use*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • fas Receptor / metabolism

Substances

  • ATG5 protein, human
  • Antineoplastic Agents, Phytogenic
  • Antioxidants
  • Apoptosis Regulatory Proteins
  • Autophagy-Related Protein 5
  • BCL2 protein, human
  • BECN1 protein, human
  • Beclin-1
  • FAS protein, human
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Plant Extracts
  • Polyphenols
  • Proto-Oncogene Proteins c-bcl-2
  • fas Receptor
  • light chain 3, human
  • Catechin
  • epicatechin gallate
  • Caspases