Multidirectional anti-melanoma effect of galactolipids (MGDG-1 and DGDG-1) from Impatiens parviflora DC. and their synergy with doxorubicin

Toxicol In Vitro. 2021 Oct:76:105231. doi: 10.1016/j.tiv.2021.105231. Epub 2021 Aug 4.

Abstract

The anti-melanoma potential of galactolipids: MGDG-1 and DGDG-1, isolated from Impatiens parviflora, and their synergistic effect with anticancer drug - doxorubicin (DOX) was investigated. Both compounds demonstrated time- and dose-dependent cytotoxicity against human melanoma cells of different metastatic potential. MGDG-1 was more effective than DGDG-1, with the highest activity against A375 cell line (IC50 = 15.14 μg/mL). Both compounds acted selectively, were devoid of hepatotoxicity or mutagenicity. Additionally, MGDG-1 proved to be a tyrosinase inhibitor. Co-administration of MGDG-1 and DGDG-1 with DOX revealed a synergistic cytotoxic effect on melanoma cells. The cytotoxicity of all tested MGDG-1/DOX and DGDG-1/DOX cocktails was considerably higher than that of each agent administered alone. MGDG-1/DOX (Mix3) reduced the viability of A375 melanoma cells almost totally and this effect was 2-fold more potent as compared to DOX alone. Our study indicates that the overall effect is enhanced with the increasing concentration of MGDG-1 in the cocktail. These results open up a possibility for lowering therapeutic doses of chemotherapeutics such as doxorubicin when co-administrated with galactolipids. Thus, MGDG-1 can be prospectively considered as multidirectional anti-melanoma agent and can be recommended for further in vitro and in vivo studies, especially in search for effective combined therapy.

Keywords: Anti-melanoma; Anti-tyrosinase; Combined therapy; Digalactosyl diacylglycerol (DGDG); Impatiens; Monogalactosyl diacylglycerol (MGDG).

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Biphenyl Compounds / chemistry
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Doxorubicin / pharmacology*
  • Drug Synergism
  • Glycolipids / chemistry
  • Glycolipids / pharmacology*
  • Humans
  • Impatiens
  • Melanoma / drug therapy*
  • Monophenol Monooxygenase / antagonists & inhibitors
  • Mutagenicity Tests
  • Picrates / chemistry
  • Skin Neoplasms / drug therapy*
  • Vibrio / drug effects
  • Vibrio / genetics

Substances

  • 1-O-linolenoyl-2-O-hexadeca-7,10,13-trienoyl-3-O-galactopyranosylglycerol
  • 3-O-(6-O-galactopyranosylgalactopyranosyl)-1,2-di-O-dodecanoylglycerol
  • Antineoplastic Agents
  • Biphenyl Compounds
  • Glycolipids
  • Picrates
  • Doxorubicin
  • 1,1-diphenyl-2-picrylhydrazyl
  • Monophenol Monooxygenase

Supplementary concepts

  • Vibrio harveyi