Sara Bin Judia

The search for NF-κB blockers to optimize antioxidants and counteract inflammation and carcinogenesis has identified several promising natural compounds, encompassing curcumin. Nonetheless, despite the pleiotropic health attributes of curcumin and established safety, its in vivo efficacy is limited by its poor pharmacokinetic properties, primarily due to its low bioavailability because of its low free serum concentrations and short half-life. To overcome these restrictions, we investigated the efficacy of the synthetic curcumin analog PAC in breast cancer cells. Additionally, MCF-7 and MDA-MB-231 cell lines were employed to explore the anticancer effects of PAC by assessing cell viability, apoptosis, clonogenic survival, and the expression of NF-κB, p53, Bcl-2, and Bax. Our results validate that PAC effectively inhibits cell proliferation and induces apoptosis in a dose-dependent manner. PAC also significantly enhances the radiosensitivity of breast cancer cells, indicating a potential synergistic effect with radiation therapy. Mechanistically, PAC exerts anticancer effects by inhibiting NF-κB signaling and modulating apoptotic genes like p53, Bax, and Bcl-2. These findings highlight its potential as a breast cancer therapeutic, enhancing existing treatments.

Venom peptides are promising agents in the development of unconventional anticancer therapeutic agents. This study explored the potential of Pilosulin-3, a recombinant peptide from the venom of the Australian jack jumper ant “Myrmecia pilosula”, as a cytotoxic and radiosensitizing agent in MCF-7 and MDA-MB-231 breast cancer (BC) cell lines. Pilosulin-3’s cytotoxicity was evaluated across a wide range of concentrations using a proliferation assay. Cell cycle progression and apoptosis were examined at the inhibitory concentration 25% (IC25) and IC50 of Pilosulin-3, both with and without a 4Gy X-ray irradiation dose. Radiosensitivity was assessed at IC25 using the clonogenic survival assay. The study revealed that Pilosulin-3 exerted a concentration-dependent cytotoxic effect, with IC25 and IC50 values of 0.01 and 0.5 µM, respectively. In silico screening indicated high selectivity of Pilosulin-3 peptide, which was predicted to be the most likely anticancer agent (PROB = 0.997) with low hemolytic activity (PROP = 0.176). Although Pilosulin-3 exhibited a significant (p < 0.05) G2/M cell cycle arrest in combination with radiation, there was no discernible effect on apoptosis induction or cell survival following irradiation. In conclusion, Pilosulin-3 proved to be cytotoxic to BC cells and induced a cytostatic effect (G2/M arrest) when combined with radiation. However, it did not enhance the efficacy of cell killing by irradiation. While it holds potential as a cytotoxic agent in breast cancer treatment, its application as a radiosensitizer does not find support in these results.

Head and neck squamous cell carcinoma (HNSCC) shows wide disparities, association with human papillomavirus (HPV) infection, and prognosis. We aimed at determining HPV prevalence, and its prognostic association with overall survival (OS) in Saudi HNSCC patients. The study included 285 oropharyngeal and oral-cavity HNSCC patients. HPV was detected using HPV Linear-Array and RealLine HPV-HCR. In addition, p16INK4a (p16) protein overexpression was evaluated in 50 representative cases. Oropharyngeal cancers were infrequent (10%) compared to oral-cavity cancers (90%) with no gender differences. Overall, HPV-DNA was positive in 10 HNSCC cases (3.5%), mostly oropharyngeal (21%). However, p16 expression was positive in 21 cases of the 50 studied (42%) and showed significantly higher OS (p = 0.02). Kaplan–Meier univariate analysis showed significant associations between patients’ OS and age (p < 0.001), smoking (p = 0.02), and tumor stage (p < 0.001). A Cox proportional hazard multivariate analysis confirmed the significant associations with age, tumor stage, and also treatment (p < 0.01). In conclusion, HPV-DNA prevalence was significantly lower in our HNSCC patients than worldwide 32–36% estimates (p ≤ 0.001). Although infrequent, oropharyngeal cancer increased over years and showed 21% HPV-DNA positivity, which is close to the worldwide 36–46% estimates (p = 0.16). Besides age, smoking, tumor stage, and treatment, HPV/p16 status was an important determinant of patients’ survival. The HPV and/or p16 positivity patients had a better OS than HPV/p16 double-negative patients (p = 0.05). Thus, HPV/p16 status helps improve prognosis by distinguishing between the more favorable p16/HPV positive and the less favorable double-negative tumors.