6-Shogaol from Zingiber officinale Induces Cell Cycle Arrest via Suppression of c-Myc Protein Expression and Promotes Apoptosis in Human B-Cell Lymphoma

Int J Mol Sci. 2026 May 7;27(10):4168. doi: 10.3390/ijms27104168.

Abstract

Lymphoma is a hematological malignancy and a major non-communicable disease characterized by the uncontrolled proliferation of lymphoid cells, frequently associated with dysregulation of the cellular myelocytomatosis (c-Myc) oncogenic pathway. In this study, we investigated the anti-lymphoma potential of bioactive compounds derived from edible plants in the Zingiberaceae family, including fingerroot (Boesenbergia rotunda), turmeric (Curcuma longa), white turmeric (Curcuma mangga), zedoary (Curcuma zedoaria), and ginger (Zingiber officinale). Crude extracts from these traditionally consumed medicinal food plants were evaluated for cytotoxic effects against human B-cell lymphoma cell lines (Raji and Daudi) and compared with normal peripheral blood mononuclear cells (PBMCs). Among the tested extracts, ginger and turmeric exhibited selective cytotoxicity toward lymphoma cells. Ginger was selected for further investigation, and subsequent analyses identified 6-shogaol as the principal active compound. 6-Shogaol significantly suppressed total and phosphorylated c-Myc protein expression, induced dose-dependent apoptosis, and caused cell cycle arrest in lymphoma cells. Network pharmacology and pathway enrichment analyses suggested the modulation of multiple oncogenic signaling pathways, particularly the PI3K/Akt/c-Myc and MAPK signaling. These findings indicate that 6-shogaol exerts anti-lymphoma activity through the coordinated modulation of oncogenic and apoptotic pathways. However, as this study is limited to in vitro and computational analyses, further in vivo validation is required. Overall, 6-shogaol represents a promising food-derived lead compound for the development of novel therapeutic strategies against lymphoma.

Keywords: 6-shogaol; Zingiber officinale; apoptosis; bioactive food compounds; c-Myc; cancer; ginger; lymphoma; nutraceutical.

MeSH terms

  • Antineoplastic Agents, Phytogenic* / pharmacology
  • Apoptosis* / drug effects
  • Catechols* / chemistry
  • Catechols* / pharmacology
  • Cell Cycle Checkpoints* / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Lymphoma, B-Cell* / drug therapy
  • Lymphoma, B-Cell* / genetics
  • Lymphoma, B-Cell* / metabolism
  • Lymphoma, B-Cell* / pathology
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • Proto-Oncogene Proteins c-myc* / genetics
  • Proto-Oncogene Proteins c-myc* / metabolism
  • Signal Transduction / drug effects
  • Zingiber officinale* / chemistry

Substances

  • Catechols
  • Proto-Oncogene Proteins c-myc
  • shogaol
  • Plant Extracts
  • MYC protein, human
  • Antineoplastic Agents, Phytogenic