Lung cancer is one of the most lethal forms of cancer known to man, affecting millions of individuals worldwide. Despite advancements being made in lung cancer treatments, the prognosis of patients with the disease remains poor, particularly among patients with late‑stage lung cancer. The elucidation of the signaling pathways involved in lung cancer is a critical approach for the treatment of the disease. Over the past decades, accumulating evidence has revealed that Rho‑associated kinase (ROCK) is overexpressed in lung cancer and is associated with tumor growth. The present review discusses recent findings of ROCK signaling in the pathogenesis of lung cancer that were conducted in pre‑clinical studies. The significant role of ROCK in cancer cell apoptosis, proliferation, migration, invasion and angiogenesis is discussed. The present review also suggests the use of ROCK as a potential target for the development of lung cancer therapies, as ROCK inhibition can reduce multiple hallmarks of cancer, particularly by decreasing cancer cell migration, which is an initial step of metastasis.

Tissues become more rigid during tumorigenesis and have been identified as a driving factor for tumor growth. Here, we highlight the concept of tissue rigidity, contributing factors that increase tissue rigidity, and mechanisms that promote tumor growth initiated by increased tissue rigidity. Various factors lead to increased tissue rigidity, promoting tumor growth by activating Focal adhesion kinase (FAK) and Rho-associated kinase (ROCK). Consequently, result in recruitment of Cancer-associated fibroblasts (CAFs), epithelial-mesenchymal transition (EMT) and tumor protection from immunosurveillance. We also discussed the rationale for targeting tumor tissue rigidity and its potential for cancer treatment.

Christia vespertilionis (L.F) Bakh. F. (red butterfly wing) is commonly used as a herbal medicine to treat symptoms of many diseases. The present study aimed to determine the in vitro antimalarial and cytotoxic activities as well as investigate the chemical compositions of the methanolic extract of C. vespertilionis leaves (CVME). The antimalarial activity of CVME against a chloroquine-sensitive (3D7) strain of Plasmodium falciparum was assessed by using a malarial SYBR Green I fluorescence-based (MSF) assay. The cytotoxic effect of CVME on cancerous (MDA-MB-231 and MCF-7) and noncancerous (NIH/3T3) cell lines were evaluated by using methyl tetrazolium (MTT) assay. Chemical constituents of CVME were analysed by using a gas chromatography/mass spectrometry (GCMS). CVME exhibited a moderate antimalarial activity with an IC50 value of 43.87 ± 2.04 µg/mL. CVME is considered as weak cytotoxic and significantly inhibited proliferation of MDA-MB-231 cells with an IC50 value of 37.45 ± 1.05 µg/mL (p100 μg/mL) and NIH/3T3 cells (IC50>100 μg/mL). This effect is selectively cytotoxic towards certain cancerous cells only. GCMS analysis suggests that CVME potentially contains several pharmacologically bioactive compounds such as tetrahydro-2-methyl- thiophene (61.77%), phytol (8.59%), 10-undecenoic acid (5.00%), 6-methyl heptyl-2-propanoate (4.96%) and 2-(2-benzothiazolylthio)-1-(3,5-dimethylpyrazolyl)-ethanone (2.70%) that might possess antimalarial and cytotoxic activities. It implies that CVME has selective cytotoxic activity against the breast cancer cell line (MDA-MB-231) and possesses an antimalarial activity against the 3D7 malaria parasite, suggesting the presence of bioactive compounds in C. vespertilionis leaves that could be a potential source of phytochemicals with high medicinal value to be used in cancer and malaria treatment. Keywords: Christia vespertilionis, antimalarial activity, anticancer activity, cytotoxic activity, bioactive compounds.

Increased tissue rigidity is an emerging hallmark of cancer as it plays a critical role in promoting cancer growth. However, the field lacks a defined characterization of tissue rigidity in dual-stage carcinogenesis of lung squamous cell carcinoma (SCC) in vivo. Pre-malignant and malignant lung SCC was developed in BALB/c mice using N-nitroso-tris-chloroethylurea (NTCU). Picro sirius red staining and atomic force microscopy were performed to measure collagen content and collagen (diameter and rigidity), respectively. Then, the expression of tenascin C (TNC) protein was determined using immunohistochemistry staining. Briefly, all tissue rigidity parameters were found to be increased in the Cancer group as compared with the Vehicle group. Importantly, collagen content (33.63 ± 2.39%) and TNC expression (7.97 ± 2.04%) were found to be significantly higher (p < 0.05) in the Malignant Cancer group, as compared with the collagen content (18.08 ± 1.75%) and TNC expression (0.45 ± 0.53%) in the Pre-malignant Cancer group, indicating increased tissue rigidity during carcinogenesis of lung SCC. Overall, tissue rigidity of lung SCC was suggested to be increased during carcinogenesis as indicated by the overexpression of collagen and TNC protein, which may warrant further research as novel therapeutic targets to treat lung SCC effectively.

Mice have served as an excellent model to understand the etiology of lung cancer for years. However, data regarding dual-stage carcinogenesis of lung squamous cell carcinoma (SCC) remain elusive. Therefore, we aim to develop pre-malignant (PM) and malignant (M) lung SCC in vivo using N-nitroso-tris-chloroethylurea (NTCU). BALB/C mice were allotted into two main groups; PM and M groups which received treatment for 15 and 30 weeks, respectively. Then, the mice in each main group were allotted into three groups; control, vehicle, and cancer (n = 6), which received normal saline, 70% acetone, and 0.04 M NTCU by skin painting, respectively. Histopathologically, we discovered a mix of hyperplasia, metaplasia, and dysplasia lesions in the PM group and intracellular bridge; an SCC feature in the M group. The M group was positive for cytokeratin 5/6 protein which confirmed the lung SCC subtype. We also found significantly higher (P < 0.05) epithelium thickness in the cancer groups as compared to the vehicle and control groups at both the PM and M. Overall, this study discovered that NTCU is capable of developing PM and M lung SCC in mice model at appropriate weeks and the vehicle group was suggested to be adequate as control group for future research.

Mitochondrial DNA (mtDNA) is integral to cellular function. Alterations in mtDNA can lead to significant disruptions in mitochondrial function, including cellular energy production, metabolism, and apoptosis regulation. Mitochondrial dysfunction has emerged as a crucial factor in the progression of cancer, including head and neck squamous cell carcinoma (HNSCC). Based on a literature search conducted from August 2024 to March 2025 on PubMed and Google Scholar, our review summarizes the relevance of mtDNA alterations in HNSCC development. HNSCC has been found to cause significant variations in mtDNA, including mutations, copy number variations (or known as mtDNA content) and large-scale deletions. Notably, these alterations varied by disease stage, different key aspects of mitochondrial function, such as cellular growth, senescence, metabolism and apoptosis, and cell-specific genetic context. We further suggest that drugs that modulate mitochondrial pathways, mitochondrial transplantation, and gene-editing technologies, are future treatment strategies for HNSCC. Lastly, we discuss the potential of co-roles of nuclear DNA mutations with mtDNA alterations in HNSCC to provide a holistic view of HNSCC pathogenesis and the possibility for combined therapeutic strategies in HNSCC.