Background and Aims: Chemotherapy uses agents that selectively target cancer cells but can also cause collateral damage to healthy tissues and lead to significant side effects. These toxic agents have major adverse effects on noncancerous tissues. It is therefore imperative to develop safe and efficacious alternative therapeutic strategies capable of inducing apoptosis. The aim of the present study was to evaluate in vitro how postbiotics derived from heat‐killed Lactobacillus acidophilus LA‐5 affect human prostate cancer cells.Methods: Lactobacillus acidophilus LA‐5 strain was cultured in MRS broth at a concentration of 10⁹ colony forming units (cfu) per milliliter. The activated probiotics were then heat treated at 75°C for 60 min to inactivate them and postbiotics were obtained. The inhibitory effects of heat‐killed Lactobacillus acidophilus LA‐5 on LNCaP and PC3 cells were assessed through an MTT assay. The apoptotic impact of postbiotics on the cells was validated using Hoechst 33342/propidium iodide (HO/PI) staining. Additionally, western blotting was employed to examine the expression of cytochrome‐c (cyt‐c), Bcl2, Bax, and caspase‐3–9 proteins associated with the apoptotic pathway. Additionally, the levels of antioxidant and oxidant enzymes were measured in both cell lines using established colorimetric methods and commercial kits.Results: MTT results showed that the postbiotic Lactobacillus acidophilus LA‐5 had IC50 values of 10⁷ and 10⁸ cfu/mL on LNCaP and PC3 cells, respectively. HO/PI results showed postbiotic‐induced apoptosis in both cell lines. Heat‐killed Lactobacillus acidophilus LA‐5 increased the expression of cyt‐c, caspase‐9, Bax, and caspase‐3 protein levels and decreased Bcl2 expression in LNCaP and PC3 cell lines. However, caspase‐8 was not detected. In addition, high‐dose postbiotic Lactobacillus acidophilus LA‐5 (10⁸ and 10⁹ cfu/mL) increased the activity of oxidants ROS and MDA and suppressed the activity of antioxidants GSH, SOD, and CAT.Conclusions: This study demonstrated that postbiotic Lactobacillus acidophilus LA‐5 from heat inactivation could cause apoptosis and impede the proliferation of LNCaP and PC3 prostate cancer cells in vitro.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease marked by mucosal inflammation, oxidative stress, and increased apoptosis. This study investigated the therapeutic effects of UV‐C‐inactivated Lacticaseibacillus casei 39 (paraprobiotic) in an acetic acid‐induced UC rat model. The study evaluated its effects on clinical symptoms, inflammatory cytokines, oxidative stress, growth factor expression, PI3K/AKT pathway activation, and apoptotic markers. Paraprobiotic was obtained by UV‐C inactivation of 10 ⁸ CFU/mL L. casei 39. Female Wistar rats were divided into four groups: Control, UC, UC + Probiotic, and UC + Paraprobiotic ( n = 10/group for clinical, ELISA, and oxidative stress analyses; n = 3 pooled/group for Western blot). UC was induced by rectal acetic acid administration, followed by daily oral treatments for 6 days. Clinical signs (DAI, weight change), plasma/tissue cytokines (ELISA, Western blot), oxidative stress (colon TOC/TAC), VEGF/EGF mRNA (qRT‐PCR), and apoptosis/PI3K/AKT pathway proteins (Western blot) were assessed. The UC group showed severe colitis, increased TNF‐α and IL‐6, decreased IL‐10, elevated TOC, reduced TAC, altered VEGF/EGF mRNA, PI3K/AKT activation, and increased apoptosis (Bax/Bcl‐2 ratio, Cytochrome c, Caspase‐9, Caspase‐3). Paraprobiotic treatment improved clinical symptoms, reduced pro‐inflammatory cytokines, and increased anti‐inflammatory cytokines, modulated growth factor expression, reduced oxidative stress, suppressed PI3K/AKT signaling, and downregulated apoptotic markers. TOC decreased 2.10‐fold ( p < 0.01), TAC increased 5.43‐fold ( p < 0.001), and Bax/Bcl‐2 ratio and Caspase‐3 expression were significantly reduced ( p < 0.001 vs. UC; Caspase‐3 also p < 0.05 vs. UC + Probiotic). L. casei 39 paraprobiotic exhibits potent anti‐inflammatory, antioxidant, and anti‐apoptotic effects in UC, suggesting its promise as a novel, multi‐target therapeutic agent.

Hepatocellular carcinoma (HCC) presents a significant therapeutic challenge, necessitating novel approaches beyond conventional treatments. This study investigates the combined cytotoxic effects of nano-titanium dioxide (nano-TiO₂), copper (II) phthalocyanine (CuPc), and copper (II) phthalocyanine–modified nano-TiO₂-(nano-TiO₂/Pc) on HepG2 hepatocellular carcinoma cells using sonodynamic therapy (SDT), photodynamic therapy (PDT), and sonophotodynamic therapy (SPDT). The results show that individual treatments with nano-TiO₂ or CuPc alone did not induce significant cytotoxicity. However, when combined with SDT or PDT, a noticeable decrease in cell viability was observed. Strikingly, SPDT combined with nano-TiO₂/Pc demonstrated the most significant cytotoxic effect, achieving up to 83.80% apoptosis in HepG2 cells. This was associated with a marked reduction in Bcl-2 protein levels and an increase in cleaved caspase-3, cleaved caspase-9, cytochrome-c (cyt-c), and Bax indicating the activation of both intrinsic and extrinsic apoptotic pathways. Furthermore, SPDT-nano-TiO₂/Pc significantly increased oxidative stress, as evidenced by decreased levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), along with elevated levels of malondialdehyde (MDA). These findings suggest that phthalocyanine-mediated SPDT effectively enhances mitochondrial apoptosis and disrupts the tumor cytoplasmic membrane, highlighting the potential of combining SDT and PDT with nano-TiO₂/Pc as a promising strategy for cancer treatment. Graphical Abstract

Aim: The aim of this study was to investigate the effects of glutathione (GSH) on chemotherapy-related toxicities in MCF-7 breast cancer cell line treated with paclitaxel (PTX) by cell viability and oxsidative stres parameters. Materials and Methods: Cells were treated with glutathione (2.5-20 mM) and paclitaxel (0.001-100 µM) for 24, 48 and 72 hours, after which cell viability was determined by WST-1 assay. IC50 values were calculated from the data obtained. Following combination analyses, the combination index was calculated and the levels of glutathione, total oxidant species (TOS) and total antioxidant species (TAS) were measured in cell lysates exposed to the indicated combinations for 72 hours. Results: In the study, it was determined that the cytotoxic effect of paclitaxel decreased as the amount of glutathion used in the combinations increased and glutathion concentrations above 10 mM showed antagonistic effect with paclitaxel. Conclusion: In patients with breast cancer, the administration of appropriate doses of glutathione in combination with chemotherapy may prove beneficial in reducing the adverse effects associated with oxidative stress.

Milk-delivered postbiotics from Bifidobacterium animalis BB-12 modulate gut microbiota composition, increase short-chain fatty acid production, and regulate systemic immune responses in vivo .