Association of AP-1/c-Jun with IL-6 and IL-8 expression in hepatocellular carcinoma: attenuating effects of metformin in vitro

Effect of 6-gingerol on proliferation and apoptosis of ovarian cancer cells by the PI3K/AKT/mTOR pathway

Background As a major contributor to mortality among gynecological malignancies, ovarian cancer highlights an urgent need for novel therapeutic approaches. Although 6-gingerol—a primary bioactive compound found in ginger—is recognized for its anticancer properties, its precise role and underlying mechanisms in ovarian cancer remain largely unexplored. Methods SKOV3 ovarian cancer cells were treated with varying concentrations of 6-gingerol, either alone or in combination with Recilisib, an activator of the PI3K signaling pathway. Cell viability was evaluated using the MTT assay, whereas apoptosis and cell cycle distribution were assessed via flow cytometry. Western blot analysis was conducted to measure protein levels of cyclin E, cyclin B, Beclin1, Atg7, and P62. Results 6-gingerol treatment led to a concentration-dependent reduction in cell viability, induced G2-M phase arrest, and promoted apoptosis. These changes were associated with elevated expression of Beclin1 and Atg7, alongside decreased levels of cyclin E, cyclin B, and P62 (p < 0.05). Notably, co-treatment with Recilisib significantly counteracted the effects of 6-gingerol on cell viability, cell cycle regulation, apoptosis, and the expression of autophagy-related proteins (p < 0.05). Conclusion These findings indicate that 6-gingerol may exert antitumor activity in ovarian cancer cells through inhibition of the PI3K/AKT/mTOR pathway, resulting inreduced cell viability, enhanced apoptosis, and increased autophagic activity. The pivotal involvement of this signaling cascade is supported by the observation that its targeted activation effectively reverses the actions of 6-gingerol. Collectively, these results support further investigation into the biological effects of 6-gingerol in ovarian cancer models.

Insulin-Induced NF-κB Activation May Contribute to Doxorubicin Resistance in Luminal A T-47D Breast Cancer Cells

Doxorubicin is an effective chemotherapy agent for breast cancer; however, its efficacy is often limited by cellular resistance. Insulin is hypothesized to enhance anti-apoptotic activity through activation of Nuclear Factor Kappa-Beta (NF-κB), although its mechanism in the Luminal A subtype T-47D cell line has not been extensively studied. This analytical experimental study with a post-test only paired design used T-47D cells divided into insulin-treated and non-insulin groups. Both groups were exposed to various concentrations of doxorubicin, namely 0 (control), 3.125, 6.25, 12.5, 25, 50, and 100 µg/mL. NF-κB activation was measured as pNF-κB concentration using the ELISA method. Data were analyzed using the Shapiro–Wilk test for normality followed by a paired t-test. The insulin-treated group showed higher mean pNF-κB concentrations compared to the non-insulin group across all doxorubicin doses. Significant differences were observed at 0 µg/mL (p = 0.008), 3.125 µg/mL (p = 0.009), and 100 µg/mL (p = 0.045), whereas no significant differences were found at concentrations between 6.25 and 50 µg/mL (p > 0.05). Overall, increasing doxorubicin concentrations reduced pNF-κB levels; however, insulin treatment maintained higher pNF-κB levels compared to the non-insulin group. These findings indicate that insulin increases NF-κB activation in doxorubicin-treated T-47D breast cancer cells and may sustain NF-κB activity against the cytotoxic effects of doxorubicin.

Modulatory Effects of IL-24 on Autophagy and Apoptosis in Large Cell Lung Carcinoma

Large cell lung carcinoma (LCLC) is a highly aggressive, undifferentiated subtype of non-small cell lung cancer characterized by rapid metastasis and resistance to traditional systemic chemotherapies. Targeted immunotherapies using cytokines like Interleukin-24 (IL-24) represent promising avenues to selectively induce cancer-specific cell death. This study evaluated the concentration-dependent cytotoxic and molecular modulatory effects of IL-24 on patient-derived primary LCLC cell lines. Primary LCLC cultures established from ultrasound-guided tru-cut biopsies were treated with varying concentrations of recombinant human IL-24 protein. Cell viability and growth inhibition rates were quantified using the MTT colorimetric assay. Transcriptional variations in the autophagic flux marker (LC3) and the initiator of intrinsic apoptosis (caspase-9) were evaluated using quantitative real-time PCR (RT-qPCR). MTT assay profiling demonstrated a strong concentration-dependent cytotoxic effect after 48 hours of treatment, yielding a half-maximal inhibitory concentration (IC50) of 22.9 pg/mL. Cell viability sharply collapsed from 82.5% at a sub-threshold dose of 5 pg/mL down to 14.7% at the maximum concentration of 100 pg/mL. RT-qPCR tracking showed a robust, dose-dependent upregulation of LC3 across all tested doses, indicating immediate activation of the autophagic pathway. Conversely, apoptotic response tracking revealed a distinct threshold activation; caspase-9 expression remained low at 10 pg/mL but co-elevated drastically with LC3 at higher concentrations of 50 pg/mL and 100 pg/mL. These findings validate that IL-24 exerts potent anti-cancer activity in primary LCLC by triggering excessive, toxic autophagy that drives past a cytoprotective survival threshold, successfully engaging the ATG4/ATG5 molecular switch to orchestrate a fatal transition into the intrinsic mitochondrial apoptotic pathway. Consistently supported by quantitative alignment between gene upregulation and loss of viability, IL-24 proves to be a compelling therapeutic candidate that warrants advanced in vivo evaluation.

Combined effects of EGCG and retinol on viability and apoptosis-related gene expression in Caco-2 and HCT-116 colon cancer cells

Objective(s): Colorectal cancer remains a leading cause of cancer-related deaths worldwide, emphasizing the need for novel therapeutic strategies. Epigallocatechin-3-gallate (EGCG), a major green tea polyphenol, and retinol, a vitamin A derivative with antioxidant properties, have shown anti-cancer activity individually. This study investigates the combined effects of EGCG and retinol on human colorectal cancer cell lines, Caco-2 and HCT-116. Materials and Methods: Cytotoxic effects of EGCG and retinol, alone and in combination, were evaluated using resazurin-based cell viability assays. Intracellular reactive oxygen species (ROS) levels were measured by DCFDA assay to assess antioxidant activity. Changes in expression of apoptosis- and survival-related genes (p53, p21, AKT, and NF-κB) were analyzed using quantitative real-time PCR (RT-qPCR). Results: Combined treatment with EGCG and retinol reduced cell viability and intracellular ROS levels in both Caco-2 and HCT-116 cells. This treatment also modulated gene expression by increasing pro-apoptotic markers (p53 and p21) and decreasing anti-apoptotic markers (AKT and NF-κB), suggesting enhanced regulation of apoptosis-related pathways and inhibition of survival signaling. Conclusion: The combined effects of EGCG and retinol result in enhanced cytotoxicity, antioxidant activity, and modulation of apoptosis- and survival-related genes in colorectal cancer cells, supporting their potential as a combined therapeutic approach. Further studies are required to confirm these findings and explore clinical relevance.

Insulin Enhances NF-κB Activation in Luminal A T -47D Breast Cancer Cells Exposed to Low-Dose Doxorubicin

Zeylenone-mediated inhibition of TIMP-1-induced Bax/Bcl-2/Cle-caspase-3 expression and apoptosis via FAK-PI3K/AKT pathway regulation in thyroid cancer cells: in vitro and in silico study