Background: Cervical cancer is a type of cancer that originates from the endometrium and is more common in developed countries and its incidence is increasing day by day in developing countries. The most commonly prescribed chemotherapeutic drugs limit their use due to serious side effects and the development of drug resistance. For this reason, interest in new active ingredients obtained from natural products is increasing. This study aimed to reveal the apoptotic and antiproliferative effects of gallic acid and doxorubicin combination therapy against the HeLa cell line. Methods: We investigated the anti-cancer effects of doxorubicin and gallic acid in the human HeLa cervical cell line by using the MTT test, Nucblue staining for the identification of apoptotic cells due to nuclear condensation using fluorescent substance, and apoptotic markers P53 and Bax for the RT-PCR test. Results: The highest cytotoxic effect obtained in the study, the highest increase in apoptotic induction, and a significant difference in P53/Bax levels were seen in the gallic acid/doxorubicin combination. Additionally, it was determined that gallic acid exhibited an effective cytotoxic effect on HeLa and HaCat cells within 48 and 72 h of application. Conclusions: The obtained findings show that the gallic acid/doxorubicin combination applied to HeLa cells may be an alternative treatment against both the cytotoxic effect size and the side effects of the chemotherapy agent.

Cervical cancer is a major gynecological malignancy linked to hormonal dysregulation and genetic alterations. Chemotherapy is standard but limited by toxicity and chemoresistance, prompting interest in plant-derived adjuncts. This study examined the anticancer and immunomodulatory effects of Hesperidin (Hes), a citrus flavonoid, with Doxorubicin (DX) in HeLa cervical cancer cells. Cell viability was assessed by MTT assay, apoptotic markers (Bcl-2, Caspase-3) by RT-qPCR, and inflammatory cytokines (IL-1β, IL-6, TNF-α, IFN-γ) by ELISA. Cytokine levels were normalized to 10⁴ viable cells, and mRNA expression of all four cytokines was quantified by RT-qPCR, confirming protein-level changes and showing the strongest IL-6 suppression with Hes+DX. Chou–Talalay combination index (CI) analysis demonstrated synergistic interactions (CI < 1.0) between Hes and DX across all tested concentrations, with strong synergism (CI < 0.7) at medium and high doses, particularly at 48 and 72 h. Hes alone showed dose-dependent cytotoxicity, while the combination markedly increased Caspase-3, reduced Bcl-2, and decreased IL-1β, IL-6, and TNF-α, indicating enhanced intrinsic apoptosis and complementary immunomodulation. These results suggest that Hes augments DX’s pro-apoptotic and anti-inflammatory effects, potentially allowing lower chemotherapy doses and reduced systemic toxicity in cervical cancer treatment.

Background/Objectives: Ovarian cancer has the highest mortality rate in the world. Treatment methods are listed as surgery, chemotherapy, and radiotherapy, depending on the stage of cancer, but developing resistance to chemotherapy increases the need for alternative agents that act on the same pathways. The effects of rosmarinic acid (RA) and doxorubicin (DX) on the activation of FOXP3, an important tumor suppressor gene, in OVCAR3 cells were examined. Materials and Methods: In this study, a human ovarian adenocarcinoma cell line was used. MTT analysis was performed to reveal the result of RA and DX on ovarian cancer cell proliferation. Expression levels of FOXP3 for cell proliferation and Capase-3 for apoptosis were determined by RT-qPCR. The wound healing model was applied to determine cell migration rates. The results were evaluated with one-way ANOVA in an SPSS 20.0 program as p ≤ 0.05. Results: It was determined that RA and DX alone and in combination inhibited the proliferation of OVCAR3 cells in different doses for 24, 48, and 72 h, and caused the cells to die by causing them to undergo apoptosis. Caspase-3 expression increased approximately tenfold in OVCAR3 cells, while FOXP3 expression was upregulated only in RA treatment and was downregulated in DX and RA + DX treatments. Conclusions: According to the results of our study, it was determined that the FOXP3 signaling pathway related to apoptosis, and proliferation was affected by the combination treatment of RA and DX in the OVCAR3 cancer cell line. This shows that RA will gain an important place in cancer treatment with more comprehensive study.

Background/Objectives: Ovarian cancer remains one of the most commonly diagnosed malignancies among women worldwide. The heterogeneity among tumor subtypes and the emergence of treatment resistance have raised significant concerns regarding the long-term efficacy of chemotherapy, radiotherapy, and immunotherapy. In response to these challenges, drug repurposing strategies—utilizing existing drugs in novel therapeutic contexts—have gained increasing attention. This study aimed to investigate the cytotoxic and apoptotic effects of the combined application of doxorubicin (DX) and thymoquinone (TQ) on ovarian adenocarcinoma cells (OVCAR3). Methods: OVCAR3 cells were cultured in RPMI medium supplemented with 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin. Cell viability and proliferation were assessed using the MTT assay following treatment with various concentrations of DX and TQ. NucBlue immunofluorescence staining was employed to examine nuclear morphology and to identify apoptosis-associated changes. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) was per-formed to evaluate the expression levels of apoptosis-related and oncogenic pathway genes, including RAF, RAS, Bcl-2, and Bax. Results: The results demonstrated that the combination of DX and TQ significantly reduced OVCAR3 cell viability and induced apoptosis in a dose-dependent manner. qRT-PCR analysis revealed a downregulation of RAS, RAF, and Bcl-2 expression, along with an upregulation of Bax, indicating activation of the intrinsic apoptotic pathway. These findings suggest that thymoquinone exerts an-ti-proliferative and pro-apoptotic effects by modulating the RAS/RAF signaling cascade. Furthermore, the co-administration of thymoquinone with doxorubicin potentiated these effects, suggesting a synergistic interaction between the two agents. Conclusions: Histopathological and molecular evaluations further confirmed the activation of apoptosis and the suppression of key oncogenic pathways. Collectively, these results underscore the therapeutic potential of thymoquinone as both a monotherapy and an adjuvant to conventional chemotherapy, warranting further validation in preclinical and clinical studies.

The aim of this study was to determine the protective and antioxidative effects of intensive exercise on streptozotocin (STZ)-induced testicular damage, apoptotic spermatognial cells death, and oxidative stress. 36 male Sprague Dawley rats were divided into three groups: control, diabetes, and diabetes+intensive exercise (IE) groups. Testicular tissues were examined histopathologically and antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) activity, as well as serum testosterone level, were measured. Seminiferous tubules and germ cells were found to be better in the testis tissue of the intense exercise group than in the diabetes group. Diabetes suppressed antioxidant enzymes CAT, SOD, GPx and testosterone levels were significantly decreased, and increased MDA level in the diabetic group compared to diabetes+IE group (p < 0.001). Following four weeks of treatment, intensive exercise improved the antioxidant defense, significantly decreased MDA activity, and increased testosterone levels in testicular tissue in the diabetic group compared to diabetes+IE group (p < 0.01). STZ-induced diabetes causes damage to the testis tissue. In order to prevent these damages, exercise practice has become very popular nowadays. In present study, our intensive exercise protocol, histological, and biochemical analysis of the effect of diabetes on the testicular tissues is shown.

The limitations in cancer treatment and the inadequacy of classical methods have made it necessary to discover therapeutics in cancer treatment. The cytotoxicity of thymoquinone, which has quite different properties in terms of biological activities, in ovarian cancer cells, and the changes in the expression levels of apoptotic genes (p53/caspase-3 (casp-3)) were investigated.