The c-Myc protein, a key regulator of cell proliferation, growth, and apoptosis in B-cell lymphocytes, is frequently dysregulated in Burkitt’s lymphoma. Zingiberaceae plants—galangal (Alpinia galanga), black turmeric (Curcuma aeroginosa), black ginger (Kaempferia parviflora), phlai lueang (Zingiber montanum), and phlai dum (Zingiber ottensii)—are traditionally used as herbal remedies and may serve as natural anti-lymphoma agents. In this study, extracts from these five plants were screened for cytotoxicity against Raji and Daudi lymphoma cell lines and compared with their effects on normal peripheral blood mononuclear cells (PBMCs). Galangal extract exhibited the strongest cytotoxic effects on lymphoma cells. Its major bioactive compounds, galangin and 1′-acetoxychavicol acetate (ACA), showed selective cytotoxicity, with ACA being more potent. ACA significantly suppressed both c-Myc and phosphorylated c-Myc (p-c-Myc) protein levels and induced dose-dependent apoptosis in lymphoma cells. Cell cycle analysis revealed arrest at specific phases, supporting its anti-proliferative action. Furthermore, network pharmacology and pathway enrichment analyses implicated ACA in the modulation of oncogenic PI3K-Akt and MAPK pathways. These findings highlight ACA as a promising plant-derived therapeutic candidate for lymphoma, acting through c-Myc suppression, cell cycle arrest, and apoptosis induction.

Lymphoma remains a major hematological malignancy associated with treatment resistance and systemic toxicity, highlighting the need for novel anticancer agents derived from natural products. In this study, dicentrine (5), an aporphine alkaloid isolated from Stephania venosa, was investigated for its anti-lymphoma activity in Raji and Ramos cells. Among the isolated compounds, dicentrine (5) exhibited the strongest cytotoxic activity, with IC₅₀ values of 9.03 ± 0.53 and 5.16 ± 0.44 µg/mL in Raji and Ramos cells, respectively, while demonstrating favorable selectivity toward lymphoma cells relative to peripheral blood mononuclear cells (PBMCs). Dicentrine (5) significantly suppressed c-Myc and phosphorylated c-Myc expression, reduced lymphoma cell proliferation, and decreased total viable cell numbers in a dose-dependent manner. Cell cycle analysis revealed G0/G1 arrest in Raji cells and G2/M arrest in Ramos cells. Furthermore, dicentrine (5) induced apoptosis, as evidenced by increased Annexin V-positive populations and elevated cleaved caspase-3 expression. Molecular docking analysis demonstrated strong binding affinities of dicentrine (5) toward Akt, PI3K, caspase-3, and caspase-9, while network pharmacology identified AKT1 and the PI3K/Akt signaling pathway as potential targets associated with lymphoma suppression. Western blot analysis further demonstrated that dicentrine (5) significantly reduces total Akt protein expression. Overall, the present findings indicate that dicentrine (5) suppresses lymphoma progression by inhibiting cell proliferation and promoting apoptotic cell death, highlighting its potential as a promising natural therapeutic candidate for lymphoma.

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.