Anti-Cancer Agents in Medicinal Chemistry - Volume 26, Issue 3, 2026

The smooth muscle α-actin 2-antisense 1 (ACTA2-AS1), also known as ZXF1, is an emerging cancer-associated long non-coding RNA (lncRNA) that has garnered significant attention in recent years. ACTA2-AS1 is situated on human chromosome 10 at location 10q23.31, comprising five exons and a single transcript. The aberrant expression of ACTA2-AS1 has been noted in 10 malignant tumors, correlating significantly with unfavorable clinicopathological characteristics and poor patient prognosis.

This review encapsulates recent progress in ACTA2-AS1 research, examining its expression profile, biological functions, molecular mechanisms, and anticipated influence on cancer diagnosis, treatment, and prognosis, emphasizing its potential as a novel therapeutic target based on lncRNA and its prognostic utility as a biomarker.

Based on a comprehensive search of the PubMed database for the biological function of lncRNA ACTA2-AS1 in malignant tumors, the current research is systematically summarized and critically analyzed.

ACTA2-AS1 plays a complex role in various biological processes in tumor cells, encompassing proliferation, apoptosis, and cell cycle arrest. It also contributes to migration, invasion, epithelial-mesenchymal transition (EMT), and drug resistance. Mechanistically, ACTA2-AS1 influences oncogenic or tumor-suppressive effects via a complex regulatory network. It can adsorb specific 5 miRNAs as competitive endogenous RNAs (ceRNAs), thereby mitigating the suppression of downstream mRNA targets implicated in tumorigenesis (e.g., SOX7, KLF9, CXCL2, BCL2L11, etc.) and modulating their downstream signaling pathways (e.g., Wnt5a/PKC, SMAD3, mTOR, etc.), demonstrating a broad spectrum of dual roles in carcinogenesis and tumor suppression.

ACTA2-AS1 is a promising biomarker and molecular target for the treatment of cancer.

PD-L1 plays a pivotal role as an immunoregulatory checkpoint within the immune system, exerting a critical influence on the internal functioning and survival mechanisms of cancer cells. Our study aimed to elucidate the clinical significance of PD-L1 expression in circulating tumor cells (CTCs) derived from individuals afflicted with Hypopharyngeal and Laryngeal Cancers (HLC).

To verify the relationship between the expression of PD-L1 in CTCs in HLC and the consistency in tissue and the preliminary clinical application.

A laboratory-based experimental study was carried out at Fujian Medical University Union Hospital. CTCs were identified using an immunomagnetic positive sorting methodology. Simultaneous detection was conducted on the CTC levels among PD-L1 positive patients, aiming to ascertain the dynamic relationship between real-time CTC fluctuations and the clinicopathological indices of the patients. This investigation encompassed a cohort of 38 individuals, wherein PD-L1 expression analysis was executed to delineate CTC variations in PD-L1-positive patients.

The constructed immunolipid magnetic nano-beads demonstrated pronounced efficacy in capturing CTCs, and the lipid nanoparticles exhibited noteworthy capture efficiency coupled with minimal cytotoxic effects. The assessment of PD-L1 expression consistency between CTCs and tissue specimens revealed a substantial agreement surpassing 70%. Furthermore, inhibition of PD-L1 yielded a significant elevation in the cytokine TNF-α levels, accompanied by a concomitant reduction in IL-10 levels.

The CTC sorting system devised in this investigation boasts attributes of remarkable specificity and sensitivity. By virtue of PD-L1 expression analysis, it holds the potential to offer instructive implications for tailoring individualized treatments in clinical scenarios.

Heterocyclic compounds serve as the structural framework for many commercially available drugs and are well known for their antitumor properties.

This study aimed to evaluate the cytotoxic effects, apoptosis induction, changes in cell cycle progression, and gene expression alterations of new heterocyclic compounds and their precursors against the acute monocytic leukemia cell line THP-1 through in vitro experimentation and computational approaches.

The study employed cytotoxicity assays, flow cytometry analyses, gene expression evaluations, oral bioavailability studies, and molecular modeling. Among the compounds tested, 6, 25, and 26 demonstrated the greatest potency and selectivity, exhibiting substantially increased cytotoxicity (1.18 μM < IC50 < 7.66 μM) against the THP-1 cell line. Investigations into apoptosis induction and cell cycle changes revealed that these compounds primarily caused an increase in the number of THP-1 cells undergoing apoptosis after 48 hours of treatment. Additionally, compounds 6 and 25 induced an accumulation of cells in the G0/G1 phase in the same cell line.

Regarding gene expression, a shift in the expression profile of genes associated with apoptotic mechanisms was observed. Furthermore, in silico analysis revealed that these three active compounds potentially interact with histone deacetylase 8 (HDAC8), a protein known to be associated with cancer.

These findings underscore the potential of these compounds as candidates for the development of novel therapeutic approaches in oncology.

Lung cancer is one of the most widespread malignancies among all types of cancers. There is uncertainty in its treatment because of the selectivity. The investigation is aimed to enhance therapeutic efficacy through targeted improvements in drug selectivity and reduced toxicity by analyzing well-accepted cyclooxygenase (COX)-2, which is an enzyme target and a known therapeutic target for anti-inflammatory and antitumor agents.

The objective of the present research was to identify the most suitable counterpart for celecoxib, which would produce synergistic effects and improve the selectivity index, safety, and efficacy of targeting cancer cells.

The HOPE-62 cancer cell line and noncancerous LLC-MK2 cell line were used to analyze the activity of the prepared formulations. The effectiveness was compared by calculating the half-maximal inhibitory concentration (IC50) values of carrageenan, celecoxib, and celecoxib embedded with carrageenan. The release pattern of celecoxib from the carrageenan matrix was also determined by using a trans-diffusion cell; moreover, the binding sites of carrageenan and celecoxib were also evaluated through in silico molecular docking studies.

Carrageenan showed promising anticancer activity, with an IC50 value of 17.3±2 µM against the HOPE-62 cell line. When blended with celecoxib (15.6±2 µM), the combination achieved enhanced efficacy and improved selectivity over celecoxib alone (IC50 of 10.3±1.5 µM). In noncancerous LLC-MK2 cells, the IC50 values were observed to be significantly higher: 1484 ±6 µM in the combined formulation and with IC50 values of 559±3 µM and 878±4 µM, respectively, in celecoxib and carrageenan alone.

The carrageenan-embedded celecoxib exhibited a significant increase in the selectivity index from 32 to 144, which suggests enhanced anticancer activity with a favorable safety profile. Initially, sustained release of celecoxib from the blend was at a higher rate, but steadily maintained rates were. The In-silico docking studies also supported the synergistic activity of the combined form through separate interaction patterns without interfering with others. These findings underscore the therapeutic potential of excipient–drug blending strategies to achieve synergistic effects, excellent selectivity, and reduced toxicity in cancer treatments.

Chemotherapy faces limitations such as toxicity and resistance, necessitating novel cancer treatments. Green-synthesized zinc oxide nanoparticles (ZnO-NPs) have attracted attention for their safety, biocompatibility, and therapeutic potential. This study investigates the anticancer efficacy of ZnO-NPs synthesized using the extracellular matrix of Aspergillus biplanus against colorectal cancer cell lines (HCT-116).

ZnO-NPs were synthesized extracellularly using A. biplanus fungal extract. The nanoparticles were characterized through UV-Vis spectrophotometry, showing an absorbance peak at 375 nm, and scanning electron microscopy (SEM), which determined their morphology and size. The anticancer activity was evaluated in vitro using HCT-116 cells. Reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) were assessed to understand the mechanism of cytotoxicity. In vivo studies were proposed for further validation.

The synthesized ZnO-NPs appeared pale white and exhibited a characteristic absorbance at 375 nm. SEM revealed spherical particles ranging from 35–150 nm. The ZnO-NPs showed strong anticancer activity with an IC50 value of 40.6 µg/mL. ROS levels increased significantly in treated cells, while the MMP decreased to 77.25% compared to 100% in controls.

ZnO-NPs exerted cytotoxic effects via ROS generation and mitochondrial dysfunction. These results underscore the nanoparticles’ ability to induce apoptosis in cancer cells through oxidative stress pathways.

Biogenically synthesized ZnO-NPs from A. biplanus show promise as eco-friendly anticancer agents. Further in vivo studies are recommended to confirm their therapeutic potential.