Fustin suppressed melanoma cell growth via cAMP/PKA-dependent mechanism

Biosci Biotechnol Biochem. 2024 Jul 22;88(8):900-907. doi: 10.1093/bbb/zbae072.

Abstract

Melanoma, a cancer arising from melanocytes, requires a novel treatment strategy because of the ineffectiveness of conventional therapies in certain patients. Fustin is a flavanonol found in young fustic (Cotinus coggygria). However, little is known about its antimelanoma effects. Our study demonstrates that fustin suppresses the growth of B16 melanoma cells. Phalloidin staining of cytoskeletal actin revealed that fustin induced a conformational change in the actin structure of melanoma cells, accompanied by suppressed phosphorylation of myosin regulatory light chain 2 (MLC2), a regulator of actin structure. Furthermore, the protein kinase A (cAMP-dependent protein kinase) inhibitor H89 completely attenuated fustin-induced downregulation of phosphorylated myosin phosphatase targeting subunit 1, which is involved in dephosphorylation of MLC2. In a mouse model, administration of fustin suppressed tumor growth in B16 melanoma cells without adverse effects. In conclusion, our findings suggest that fustin effectively suppresses melanoma cell growth both in vitro and in vivo.

Keywords: cAMP; cancer; fustin; melanoma; phytochemicals.

MeSH terms

  • Actins / metabolism
  • Animals
  • Cardiac Myosins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation* / drug effects
  • Cyclic AMP* / metabolism
  • Cyclic AMP-Dependent Protein Kinases* / metabolism
  • Flavonoids / pharmacology
  • Humans
  • Isoquinolines / pharmacology
  • Melanoma / drug therapy
  • Melanoma / metabolism
  • Melanoma / pathology
  • Melanoma, Experimental* / drug therapy
  • Melanoma, Experimental* / metabolism
  • Melanoma, Experimental* / pathology
  • Mice
  • Mice, Inbred C57BL
  • Myosin Light Chains / metabolism
  • Phosphorylation / drug effects
  • Sulfonamides / pharmacology

Substances

  • Cyclic AMP-Dependent Protein Kinases
  • Cyclic AMP
  • Myosin Light Chains
  • Cardiac Myosins
  • myosin light chain 2
  • Flavonoids
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
  • Isoquinolines
  • Actins
  • Sulfonamides