Combination therapy and multitarget drugs have recently attracted much attention as promising tools to fight against many challenging diseases and, thus, represent a new research focus area. The aim of the current project was to screen multitarget compounds and to study their individual and combined effects on acetaminophen-induced liver injury. In this study, 2 of the best hepatoprotective multitargeting compounds were selected from a pool of 40 major compounds present in Curcuma longa and Cinnamomum zeylanicum by using molecular docking, ADMET profiling, and Pfizer’s rule of five. The two selected compounds, quercetin and curcumin, showed a high binding affinity for the CYP2E1 enzyme, MAPK, and TLR4 receptors that contribute to liver injury. The candidates caused the decreased viability of cancer cell lines (HepG2 and Huh7) but showed no effect on a normal cell line (Vero). Examination of biochemical parameters (ALT, AST, ALP, and bilirubin) showed the hepatoprotective effect of the candidate drugs in comparison with the control group, which was confirmed by histological findings. Taken together, quercetin and curcumin not only satisfied the drug-like assessment criterion and proved to be multitargeting by preventing liver damage but also showed anticancer activities.

Aslam J, et al. J Vet Sci. 2024 May;25(3):e47. https://doi.org/10.4142/jvs.23258

The epithelial cell adhesion molecule (EpCAM) is considered an essential proliferation signature in cancer. In the current research study, qPCR induced expression of EpCAM was noted in acute lymphoblastic leukemia (ALL) cases. Costunolide, a sesquiterpene lactone found in crepe ginger and lettuce, is a medicinal herb with anticancer properties. Expression of EpCAM and its downstream target genes (Myc and TERT) wasdownregulated upon treatment with costunolide in Jurkat cells. A significant change in the telomere length of Jurkat cells was not noted at 72 h of costunolide treatment. An in silico study revealed hydrophobic interactions between EpCAM extracellular domain and Myc bHLH with costunolide. Reduced expression of NFκB, a transcription factor of EpCAM, Myc, and TERT in costunolide-treated Jurkat cells, suggested that costunolide inhibits gene expression by targeting NFκB and its downstream targets. Overall, the study proposes that costunolide could be a promising therapeutic biomolecule for leukemia.

Glia maturation factor gamma (GMFG) overexpression increases T-cell migration and adhesion. Its high expression in colorectal and ovarian cancer is associated with chemoresistance and adverse prognosis. However, it remains elusive if GMFG plays a role in the development and progression of leukemia. Tissue invasion in leukemia has long been known as the reason for disease progression as leukemic cells accumulates in bone marrow, spleen and lymph nodes. This tissue invasion requires cell motility and migration. The aim of the present study was to find any association of GMFG expression with leukemia and its potential to be a diagnostic marker. For this purpose, we have carried out expression profiling of GMFG among a cohort of leukemia patients. Liquid biopsies were collected and subjected to GMFG expression analysis. We found that GMFG expression was significantly elevated among leukemia patients of all age groups relative to their age match controls. Further promoter analysis of GMFG reveals binding sites for T-cell Acute Lymphocytic Leukemia 1 (TAL1) and associated transcription factors. TAL1 is master transcription factor which, in coordination with other factors like GATA-binding protein 1 (GATA-1) and LIM domain only 2 (LMO2), regulates gene expression in T-cell leukemia. The induced TAL1 expression coincides with upregulated GMFG expression. Together these data suggest that TAL1 may bind to GMFG promoter to increase its expression. GMFG may play a crucial role in the motility of leukemic cells and facilitates their tissue invasion which leads to therapy resistance.