Triple-negative breast cancer (TNBC) presents a major clinical challenge due to its aggressive behavior, limited targeted therapies, and frequent development of chemoresistance. Resistance to doxorubicin (DOX), a key chemotherapeutic agent, is often associated with epithelial-mesenchymal transition (EMT), overexpression of multidrug resistance (MDR) proteins, and dysregulation of microRNAs (miRNAs). This study investigates the potential of pentagalloyl glucose (PGG), a naturally occurring polyphenol, to overcome DOX resistance in TNBC cells by targeting EMT, miRNA expression, and MDR transporter activity. DOX-resistant MDA-MB-231/ADR cells were established and characterized. The cytotoxic and chemosensitizing effects of PGG were evaluated through MTT assays, apoptosis analysis, migration and invasion assays, Western blotting, miRNA sequencing, qRT-PCR, and drug accumulation studies. PGG significantly restored DOX sensitivity in resistant TNBC cells, as demonstrated by a reduction in the half-maximal inhibitory concentration (IC₅₀) and increased apoptosis. An EMT reversal effect was observed through upregulation of E-cadherin and downregulation of ZEB1 and vimentin, accompanied by reduced cell migration and invasion. miRNA profiling revealed the upregulation of miR-200c-3p and other tumor-suppressive miRNAs. Notably, overexpression of miR-200c-3p alone enhanced chemosensitizing and DOX-induced apoptosis in MDA-MB-231/ADR cells, highlighting its role in drug sensitivity. Additionally, PGG reduced the expression of P-glycoprotein (P-gp) and multidrug resistance protein-1(MRP-1), increased intracellular DOX accumulation, and inhibited efflux activity. In conclusion, PGG reverses DOX resistance in TNBC cells through multiple mechanisms involving EMT inhibition, MDR suppression, and restoration of miR-200c-3p expression. These findings suggest that PGG holds promise as an adjuvant therapeutic agent for managing multidrug-resistant TNBC.

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.

This study systematically evaluated Escherichia coli (E. coli) expression systems for the production of a humanized single-chain variable fragment targeting interleukin-17A (hScFv-IL-17A). A wild-type hScFv (hScFv-IL-17A-WT), derived from Secukinumab, was compared with a C97S mutant (hScFv-IL-17A-C97S) in which the unpaired cysteine residue in the light-chain complementarity-determining region 3 (CDR3) was substituted with serine. The primary objectives were to identify an optimal expression system for soluble protein production and to assess the functional consequences of the C97S mutation. Protein solubility, yield, and antigen-binding properties were evaluated across expression on three E. coli strains: Origami B (DE3), SHuffle, and BL21 (DE3) incorporating the DisCoTune system. Analyses were performed using SDS-PAGE, Western blotting, enzyme-linked immunosorbent assay (ELISA), and biolayer interferometry (BLI). Among the systems tested, BL21 (DE3) with DisCoTune yielded the highest levels of soluble expression for both variants. Although the C97S mutation enhanced soluble protein yield in this system, it significantly impaired functional activity. The hScFv-IL-17A-WT exhibited a strong binding affinity (K_D = 3.64 × 10^-8 M), whereas the hScFv-IL-17A-C97S demonstrated an approximately 10-fold reduction in affinity. Competitive ELISA further confirmed that both variants recognized the same epitope as a neutralizing monoclonal antibody. Structural modeling predicted that the C97S substitution imposed a moderate stability penalty without inducing major conformational alterations, consistent with the observed reduction in binding affinity. Collectively, these findings indicate that while the C97S mutation improves soluble expression, it compromises biological activity. The hScFv-IL-17A-WT produced in BL21 (DE3) using the DisCoTune system represents the most promising candidate for subsequent therapeutic development.

Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy with poor prognosis, frequent relapse, and treatment-related toxicity. The discovery of novel anti-leukemic agents with improved selectivity remains an urgent clinical need. In this study, rhizomes of Angiopteris evecta, a medicinal plant used in Thai traditional medicine, were collected from twelve locations in Thailand and extracted using solvents of increasing polarity. Among thirty-six crude fractional extracts, the ethyl acetate crude fractional extract from source No. 003 (AE EtOAc No. 003) exhibited the strongest cytotoxic activity against KG-1a and EoL-1 leukemic cell lines, with low toxicity toward normal peripheral blood mononuclear cells. Bioactivity-guided fractionation yielded the ternary mixture, a furanone-rich mixture dominated by 5-(1-hydroxyethyl)-dihydro-2-furanone. The ternary mixture inhibited leukemic cell proliferation by inducing apoptosis, causing cell cycle arrest, and downregulating WT1 expression in EoL-1 cells. Network pharmacology and molecular docking analyses implicated AKT1, MAPK signaling, apoptosis-related pathways, and WT1 as key molecular targets. In addition, AE EtOAc No. 003 and the ternary mixture suppressed TNF-α and IL-6 production in LPS-stimulated macrophages. Collectively, A. evecta-derived furanone compounds represent promising lead candidates for anti-leukemic drug development.

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.

The XPO1 (exportin 1) gene encodes exportin 1 protein responsible for transporting proteins and RNA from the nucleus to the cytoplasm. It has been used as a biomarker for lymphoma detection. XPO1^E571K mutation has been frequently observed and identified as a good prognostic indicator for lymphoma patients. The detection of a target molecule released by lymphoma cells into blood circulation (cell-free circulating tumor DNA, cfDNA) is a better method than tissue biopsy. However, cfDNA concentration in blood circulation is very low in cancer patients. Therefore, a precise and sensitive method is needed. In this study, cfDNA was extracted, and then the XPO1 gene was detected and amplified using conventional PCR. Sanger sequencing was employed to verify the DNA sequences. FAST-COLD-PCR was developed to detect XPO1^E571K gene mutation using a CFX96 Touch Real-Time PCR System. The optimal critical temperature (Tc) was 73.3 °C, allowing selective amplification of XPO1^E571K mutant DNA while wild-type XPO1 could not be amplified. XPO1^E571K gene mutation can be detected by this method with high specificity and sensitivity in lymphoma patients. This approach facilitates rapid and straightforward detection in a timely manner after the diagnosis. Accordingly, the optimized FAST-COLD-PCR conditions can be used as a prototype for XPO1^E571K mutant detection in lymphoma patients.