Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents) - Volume 25, Issue 1, 2025

Argemone mexicana, commonly known as the Mexican prickly poppy, has been historically employed in traditional medicine for various ailments, including liver disorders. Given the rising prevalence of liver diseases, including cancer, investigating the potential efficacy of Argemone mexicana in promoting liver health is of paramount importance. This review aims to provide a comprehensive analysis of the existing literature on the hepatoprotective and anticancer properties of Argemone mexicana.

A systematic literature search was conducted across PubMed, Google Scholar, and relevant botanical and pharmacological databases. Studies from various sources, including in vitro experiments, animal models, and clinical trials, were included in the review. The search focused on articles published up to 2010-2023, encompassing research that explored the botanical characteristics, chemical composition, traditional uses, and pharmacological properties of Argemone mexicana, specifically emphasizing its impact on liver health and cancer.

The review revealed a wealth of studies highlighting the diverse pharmacological properties of Argemone mexicana. The botanical composition includes compounds with antioxidant and anti-inflammatory potential, suggesting hepatoprotective effects. Studies using in vitro and in vivo models demonstrated promising outcomes regarding liver function improvement and inhibition of liver cancer cell proliferation. While some clinical studies supported the traditional uses of Argemone mexicana, further well-designed trials are warranted to establish its clinical efficacy.

In conclusion, Argemone mexicana shows promise as a natural agent for promoting liver health and combating liver cancer. Bioactive compounds with antioxidant and anti-inflammatory properties suggest potential hepatoprotective effects. However, translating these findings into clinical practice requires further rigorous investigation, including well-designed clinical trials. This review provides a foundation for future research efforts aimed at elucidating the full therapeutic potential of Argemone mexicana in liver health and cancer management.

Although T-cell malignancies are relatively less prevalent compared to B-cell malignancies, they are highly malignant, and patients usually have poor prognoses. Employing CD7-targeted chimeric antigen receptor (CAR) T cell therapy as a novel immunotherapy to treat malignant T cells faces numerous challenges and is in its early phase. To evaluate this possibility, we aimed to review and meta-analyze the related clinical trials systematically.

On October 9, 2023, the online databases of PubMed, Scopus, Embase, and Web of Science were systematically searched for pertinent studies. After completing a two‐step title/abstract and full-text screening process, the eligible studies were included.

We observed a pooled overall response rate (ORR) of 100%. Partial response (PR), stringent and/or complete response (sCR/CR), and relapse rate were 6%, 85%, and 18%, respectively. Additionally, the pooled rate of minimal residual disease (MRD) negativity was 85%. The most common grade ≥3 adverse events were related to hematological toxicities, including neutropenia (100%), thrombocytopenia (79%), and anemia (57%). Cytokine release syndrome (CRS) was also a frequent complication with a 100% rate; however, 81% of CRS events were low grades. No grade ≥3 GVHD was reported, and the immune effector cell–associated neurotoxicity syndrome (ICANS grade ≥3) was rare (4%).

CD7 is an active and safe target that shows promising results in the treatment of relapsed and/or refractory (r/r) T-cell malignancies.

Previous studies have reported that the cGMP-specific PDE5 isozyme is overexpressed in colon adenomas and adenocarcinomas and essential for colon cancer cell proliferation, while PDE5 selective inhibitors (e.g., sildenafil) have been reported to have cancer chemopreventive activity.

This study aimed to determine the anticancer activity of a novel PDE5 inhibitor, RF26, using colorectal cancer (CRC) cells and the role of PDE5 in CRC tumor growth in vivo.

The objective of this study was to characterize the anticancer activity of a novel celecoxib derivative, RF26, in CRC cells previously reported to lack COX-2 inhibition but have potent PDE5 inhibitory activity.

Anticancer activity of RF26 was studied using human CRC cell lines. Effects on cell growth, cGMP-dependent protein kinase (PKG) activity, β-catenin levels, TCF/LEF transcriptional activity, cell cycle distribution, and apoptosis were measured. CRISPR/cas9 PDE5 knockout techniques were used to determine if PDE5 mediates the anticancer activity of RF26 and validate PDE5 as a cancer target.

RF26 was appreciably more potent than celecoxib and sildenafil to suppress CRC cell growth and was effective at concentrations that activated PKG signaling. RF26 suppressed β-catenin levels and TCF/LEF transcriptional activity and induced G1 cell cycle arrest and apoptosis within the same concentration range. CRISPR/cas9 PDE5 knockout CRC cells displayed reduced sensitivity to RF26, proliferated slower than parental cells, and failed to establish tumors in mice.

Further evaluation of RF26 for the prevention or treatment of cancer and studying the role of PDE5 in tumorigenesis are warranted.

Novel MRP modulators are needed to combat MRP-mediated multidrug resistance (MDR) in cancer cells.

Anticancer drug resistance is the main problem in cancer therapy. Causative multidrug efflux pumps are attractive target structures for the development of inhibitors of their activity.

We synthesized novel cage dimeric 1,4-dihydropyridines to evaluate them as MRP modulators in cancer cells targeting MRP1, MRP2, and MRP4.

Cage compounds were synthesized by solution dimerization of monomeric 1,4-dihydropyridines and a final functionalization reaction. The MRP modulation was determined in cellular efflux assays by the use of the flow cytometry technique as well as cellular fluorescent measurements with each fluorescent substrate of the efflux pumps.

Difluoro phenyl and methoxy or dimethoxy benzyl substitutions were most favourable for the MRP1 and MRP2 inhibition, whereas monofluor phenyl and dimethoxy benzyl substitutions were most favourable for the MRP4 inhibition.

Effective inhibitors were identified that were demonstrated to restore the respective cancer cell line sensitivity for the anticancer drug as a proof-of-concept that encourages further preclinical studies.