Bavachinin induces oxidative stress-associated apoptosis and modulates NF-κB-associated inflammatory gene expression in cervical cancer cells

NaHS inhibits cell proliferation by enhancing oxidative stress and apoptosis in HCT116 cells

Enoxaparin induces apoptosis and autophagy, modulates inflammatory signaling, and reduces oxidative DNA damage in breast and liver cancer cells.

Cancer progression involves intricate interactions between inflammatory signaling, programmed cell death mechanisms, and oxidative stress. Although enoxaparin is widely used for managing cancer-associated thrombosis, its direct cellular effects on tumor biology remain insufficiently characterized. This study aimed to evaluate the impact of enoxaparin on apoptosis, autophagy, inflammatory mediators, and oxidative DNA damage in breast (MDA-MB-231) and liver (HepG2) cancer cell lines. MDA-MB-231, HepG2, and non-cancerous HEK-293 cells were treated with varying concentrations (5, 10, 20, 40, and 80 mg/mL) of enoxaparin for 24 and 48 h. Cell viability was assessed using the MTT assay, while apoptosis was quantified by TUNEL analysis. Immunofluorescence staining was employed to evaluate the expression of NF-κB, IL-6, TNF-α, LC3, and p62. Oxidative DNA damage was determined by measuring extracellular 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels using a competitive ELISA. Statistical analyses were conducted to compare the treated and control groups. Enoxaparin significantly reduced cell viability in MDA-MB-231 and HepG2 cells without inducing cytotoxicity in HEK-293 cells. Apoptosis was markedly increased in both cancer cell lines following treatment. Enoxaparin differentially modulated inflammatory signaling; NF-κB expression was significantly increased in MDA-MB-231 cells, accompanied by suppression of IL-6 and TNF-α, whereas no significant inflammatory changes were observed in HepG2 cells. Enoxaparin treatment was observed to increase LC3 and p62 expression in both MDA-MB-231 and HepG2 cells, triggering autophagy-related pathways. Moreover, enoxaparin significantly reduced extracellular 8-OHdG levels, suggesting a reduction in oxidative DNA damage. Enoxaparin exhibits multifaceted anticancer effects by promoting apoptosis and autophagy, selectively modulating inflammatory pathways, and reducing oxidative DNA damage in breast and liver cancer cells.

Carvacrol induces apoptosis, modulates oxidative stress, and promotes G0/G1 cell cycle arrest in colorectal cancer cells.

8-gingerol from Zingiber officinale induces ER stress-mediated ferroptosis and apoptosis in ovarian cancer involving TRPV1 activation.

It is demonstrated that 8-gingerol induces coordinated apoptotic and ferroptotic cell death through a Ca2+-dependent ER stress mechanism, highlighting its potential as a novel therapeutic strategy for the treatment of ovarian cancer.

Antioxidant efficacy of N-acetylcysteine against acrylamide-induced toxicity in Leydig cells by modulating p53/Bax/Caspase-3 pathway.

Acrylamide (Acr) is a widely encountered environmental and dietary toxicant known to induce oxidative stress and disrupt male reproductive function. Leydig cells, due to their high metabolic activity and mitochondrial dependence, are particularly vulnerable to redox imbalance. N-acetylcysteine (Nac), a thiol-containing antioxidant and glutathione precursor, has been extensively studied for its cytoprotective properties. However, its modulatory effects on Acr-induced toxicity in Leydig cells and its pharmacodynamic interaction profile remain incompletely characterized. In this study, TM3 Leydig cells were exposed to Acr in the presence or absence of Nac. Cell viability was assessed by MTT assay, and chemical interaction profiles were evaluated using ZIP, Bliss, and Chou-Talalay combination index analyses. Oxidative stress parameters, including intracellular reactive oxygen species (ROS), lipid peroxidation, antioxidant enzyme activities (SOD, CAT, GPx), and glutathione levels, were measured. Apoptotic responses were analyzed through double fluorescence staining, RT-qPCR of apoptosis-related genes (Bax, Bcl2, Casp3, Trp53), and Western blot analysis of CASP3 protein expression. Acr exposure significantly reduced cell viability, increased ROS and lipid peroxidation levels, suppressed antioxidant defenses, and activated the mitochondrial apoptotic pathway. Nac treatment markedly improved cell viability, restored antioxidant capacity, reduced oxidative stress markers, and suppressed p53/Bax/Casp3-mediated apoptotic signaling. Combination analyses revealed an antagonistic interaction profile, indicating that Nac biologically limits Acr-induced cytotoxicity. Collectively, these findings demonstrate that Nac exerts protective effects in Leydig cells by modulating redox homeostasis and mitochondrial apoptosis, suggesting its potential as a protective regulator against Acr-induced reproductive toxicity.

Redox-mediated mitochondrial collapse drives intrinsic apoptotic signaling in ELT3 cells response to apigenin

Uterine leiomyoma is the most common benign gynecological tumor and a major cause of abnormal uterine bleeding, pelvic pain, and infertility. Although apigenin (API) exhibits antioxidant, antiproliferative, and anticancer activities, its mechanism of action in uterine leiomyoma, particularly the involvement of oxidative stress-mediated mitochondrial apoptosis, remains unclear. This study investigated the role of oxidative stress in API-induced apoptosis using rat uterine leiomyoma ELT3 cells. Cells were treated with 50 and 100 µM API for 48 h. Oxidative stress was assessed by measuring reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione reductase (GR) activity. Mitochondrial membrane potential (ΔΨm), cell proliferation, lactate dehydrogenase (LDH) release, and apoptosis-related gene and protein expression were also evaluated. API significantly increased ROS and MDA levels while decreasing GR activity, indicating oxidative stress. These changes were accompanied by ΔΨm collapse, reduced cell proliferation, increased LDH release, upregulation of p53, Bax, caspase-3, and caspase-9, and downregulation of Bcl-2, indicating activation of the intrinsic mitochondrial apoptotic pathway. These findings demonstrate that API induces intrinsic mitochondrial apoptosis through oxidative stress-mediated mechanisms, providing mechanistic evidence for its cytotoxic effects and supporting its potential as a phytochemical candidate for uterine leiomyoma treatment.