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

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

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

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

Bavachinin exhibited anti-inflammatory and pro-apoptotic activities against HeLa cells, likely through oxidative stress-associated apoptosis and modulation of NF-κB-associated inflammatory gene expression.

ONC212 Induces Ferroptosis-Associated Cell Death in Glioblastoma Cells

Aim: Glioblastoma (GBM) is an aggressive primary brain tumor with limited treatment options. Ferroptosis, an iron-dependent cell death characterized by lipid peroxidation and oxidative stress, is a promising therapeutic target. This study investigated the anticancer effects of the imipridone derivative ONC212 in GBM cells and examined whether its cytotoxicity involves ferroptosis-related mechanisms.Material and Methods: U87 and U251 cells were treated with increasing ONC212 concentrations. Viability was assessed by CCK-8, proliferation by BrdU incorporation (24–72 h). Ferroptosis-associated changes were evaluated by measuring ferrous iron (Fe²⁺), malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS). Expression of ferroptosis-related genes GPX4 and ACSL4 was analyzed by qRT-PCR. Ferrostatin-1 (Fer-1) was used to confirm ferroptosis involvement.Results: ONC212 reduced viability in a time- and dose-dependent manner [IC₅₀ (95% CI): 18.7 µM (17.3-20.1), 9.6 µM (8.8-10.4), and 6.2 µM (5.7-6.7) at 24, 48, and 72 h, respectively]. BrdU incorporation decreased by 46.9% and 79.4% at 24 h and 72 h, respectively, following treatment with the 24-hour IC₅₀ concentration (18.7 µM). Ferroptosis-associated oxidative stress was evident through increased Fe²⁺, MDA, ROS, and GSH depletion. ONC212 upregulated ACSL4 (2.14‑fold) and reduced GPX4 expression by 62%. Fer-1 pretreatment partially reversed these alterations, supporting the involvement of ferroptosis-associated mechanisms. Similar results were obtained in U251 cells.Conclusion: ONC212 exerts potent cytotoxic and anti-proliferative effects in GBM cells and provides preliminary evidence suggesting that it induces ferroptosis-associated cell death through modulation of oxidative stress and ferroptosis‑associated gene expression. Targeting ferroptosis with ONC212 may represent a promising therapeutic strategy for GBM.

Oxidative stress-associated mitochondrial depolarization correlates with apoptotic response in karanjin-treated cancer cells

Karanjin is a furanoflavanoid that demonstrates selective cytotoxic effects toward various cancer cells; however, its underlying mechanism has yet to be thoroughly investigated. This study aimed to elucidate the molecular mechanisms underlying karanjin-induced cytotoxicity across cancer (HeLa, MCF-7, A549, and HCT116) and healthy (HaCaT) cell lines. A combined approach integrating network pharmacology, molecular docking, and in vitro functional analyses was employed. The in vitro data showed that a high accumulation of intracellular reactive oxygen species (ROS) induced oxidative-stress-related toxicity events and subsequent cell death in cancer cells. The mitochondrial membrane potential (MMP), ATP levels, cytochrome C, and caspase 3 were more significantly affected in cancer cells (MCF-7, A549, and HCT116) as compared to healthy cells (HaCaT). Interestingly, HeLa cells were not responsive to karanjin treatment. Correlation and regression analyses indicated that mitochondrial depolarization was strongly associated with apoptosis, suggesting that mitochondrial dysfunction plays a key role downstream of oxidative stress. Network pharmacology analysis showed significant enrichment in PI3K-Akt signalling pathway, ROS regulation, and various cancer-related pathways. This suggests that ROS and the PI3K-AKT-mTOR pathway could be targets of karanjin in cancer therapy, which is supported by molecular docking and in vitro data. In conclusion, karanjin induced ROS accumulation and mitochondrial dysfunction in susceptible cancer cells (MCF-7, A549, and HCT116) in a dose-dependent manner without affecting healthy cells.

Antineoplastic Effects of Ankaferd Hemostat on Hep-2 Laryngeal Cancer Cells: Involvement of Apoptosis and PI3K/Akt/mTOR Signaling

To investigate the cellular and molecular effects of Ankaferd Hemostat on human laryngeal squamous carcinoma Hep-2 cells, with particular emphasis on cell viability, apoptosis, oxidative stress, cell cycle progression, migration, invasion, and PI3K/Akt/mTOR signaling. Hep-2 cells were treated with increasing concentrations of Ankaferd Hemostat (50-1600 nL/mL) for 24, 48, and 72 h. Cell viability, clonogenic survival, apoptosis, cell cycle distribution, migration, invasion, nuclear morphology, DNA fragmentation, intracellular reactive oxygen species (ROS) production, and expression of apoptosis- and signaling-related proteins were evaluated using established in vitro assays. Ankaferd Hemostat significantly reduced Hep-2 cell viability and clonogenic survival in a dose- and time-dependent manner. It induced apoptosis, as demonstrated by Annexin V/PI staining, nuclear fragmentation, DNA laddering, and activation of caspase-3 and PARP. Treatment also resulted in G2/M phase cell cycle arrest and increased intracellular reactive oxygen species (ROS) levels. In addition, Ankaferd Hemostat inhibited cell migration and invasion and modulated metastasis-associated proteins by downregulating MMP-2, MMP-9, and VEGF, while upregulating E-cadherin. At the signaling level, Ankaferd Hemostat suppressed the activation of the PI3K/Akt/mTOR pathway. These findings provide preclinical in vitro evidence that Ankaferd Hemostat exerts multifaceted antineoplastic effects on Hep-2 laryngeal cancer cells by modulating apoptosis, oxidative stress, cell cycle progression, migratory and invasive behavior, and intracellular survival signaling. Validation in additional laryngeal cancer models and in vivo systems is required before the translational relevance can be established.