Elucidation of anti-human melanoma and anti-aging mechanisms of compounds from green seaweed Caulerpa racemosa

Sci Rep. 2024 Nov 11;14(1):27534. doi: 10.1038/s41598-024-78464-6.

Abstract

Human melanoma is linked with aging-related disorders, prompting interest in the development of functional foods derived from natural ingredients to mitigate its incidence. Molecules in green seaweeds such as Caulerpa racemosa can serve this purpose due to their anti-tumor and anti-inflammatory properties. A previous work study compounds profiling has been carried out, and in this research the molecular docking studies targeting receptors associated with melanoma (GRP78, IRE1, BRAF) and aging (mTOR, AMPK, SIRT1) identified four promising compound in an extract of C. racemosa. The current study aims to the mechanism of those compounds at a cellular level using the human A375 (BRAF-V600E mutation) and A375 and B16-F10 cell lines. The MTT assay was used to evaluate the potential of GSCRE compounds against A375 and B16-F10 cell lines, with comparisons made to normal HDFa cell lines. Results indicated that compound C2, also known as Caulersin, demonstrated a significantly different ∆G affinity binding score compared to the control drug Dabrafenib. GSCRE crude extract, particularly C2, showed potential in modulating mTOR, AMPK, and SIRT1 pathways and downregulating GRP78, IRE1, and BRAF signaling (p < 0.05). Interestingly, C2 was less effective in suppressing A375 and B16-F10 cell lines (LD50 C2 < LD50 Dabrafenib/control), with its LD50 value nearly matching that of the Trametinib control in B16-F10 cell lines. Consequently, GSCRE, especially C2 or Caulersin, shows promise as a new molecule for developing functional foods to combat aging and human melanoma. However, further in vivo studies and clinical trials are necessary to confirm these findings.

Keywords: Antiaging; Anticancer; Caulerpa; Green seaweed; Marine algae; Melanoma; Natural product.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Aging / drug effects
  • Animals
  • Cell Line, Tumor
  • Endoplasmic Reticulum Chaperone BiP*
  • Endoribonucleases* / metabolism
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism
  • Humans
  • Melanoma* / drug therapy
  • Melanoma* / metabolism
  • Mice
  • Molecular Docking Simulation
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • Protein Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins B-raf / metabolism
  • Seaweed* / chemistry
  • Sirtuin 1 / metabolism
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Endoplasmic Reticulum Chaperone BiP
  • HSPA5 protein, human
  • Hspa5 protein, mouse
  • Endoribonucleases
  • Proto-Oncogene Proteins B-raf
  • TOR Serine-Threonine Kinases
  • ERN1 protein, human
  • Protein Serine-Threonine Kinases
  • Sirtuin 1
  • Heat-Shock Proteins
  • BRAF protein, human
  • SIRT1 protein, human
  • Plant Extracts
  • MTOR protein, human
  • AMP-Activated Protein Kinases