Stilbene B10 induces apoptosis and tumor suppression in lymphoid Raji cells by BTK-mediated regulation of the KRAS/HDAC1/EP300/PEBP1 axis

Biomed Pharmacother. 2022 Dec:156:113887. doi: 10.1016/j.biopha.2022.113887. Epub 2022 Oct 20.

Abstract

Lymphoma is a cancer of the lymphoid cells that originated in matured B or T cells. The bioactive natural compounds can efficiently treat this disease with lesser side effects. Thus, in this study, a natural stilbene B10 (3-methoxy 5-hydroxy stilbene) isolated from Cajanus cajan (Pigeon Pea) was screened for its anti-proliferative efficacy against 13 cancer cell lines. B10 showed a potential effect on the human lymphoma (Raji) cells. Cytotoxicity analysis of B10 has revealed IC50 concentrations in Raji cells at low doses (18 µM) than other cancer cell lines. The B10 could significantly cause dose and time-dependent inhibition in the proliferation of Raji cells triggering intrinsic apoptosis and S/G1 phase cellular arrest. There was an increased expression of phospho-γ-H2A.X and decreased expression of cyclin D1, causing DNA damage and cell cycle arrest, post- B10 treatments. The mitochondrial membrane potential (MMP) variations observed after B10 treatment led to changes in Bax/Bcl-2 ratio, cytochrome C release, and enhanced expression of cleaved caspase3, 9, PARP-1, and APAF-1. The B10 inhibited the proliferation of Raji cells by significantly downregulating the expression of KRAS, BTK, MDM2, P-JAK2, P-STAT3, PI3K, HDAC1/2, SIRT7, and EP300. The treatment upregulated the tumor suppressor genes PEBP1 and SAP18. Thus, the study could reveal the selective inhibitory effects of B10 on lymphoma, suggesting it as a probable innovative chemotherapeutic agent.

Keywords: BTK; EP300; Lymphoma; PEBP1; Raji; Stilbenes.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • E1A-Associated p300 Protein
  • Histone Deacetylase 1
  • Humans
  • Lymphocytes
  • Phosphatidylethanolamine Binding Protein
  • Proto-Oncogene Proteins p21(ras)
  • Stilbenes* / pharmacology

Substances

  • Stilbenes
  • Proto-Oncogene Proteins p21(ras)
  • PEBP1 protein, human
  • Phosphatidylethanolamine Binding Protein
  • KRAS protein, human
  • HDAC1 protein, human
  • Histone Deacetylase 1
  • EP300 protein, human
  • E1A-Associated p300 Protein