Search Results (30,771)

Matrix metalloproteinases (MMPs) have long been recognized as key mediators of tumor invasion and metastasis due to their capacity to degrade extracellular matrix components. However, clinical failure of broad-spectrum MMP inhibitors has revealed a more complex and context-dependent role for these proteases in cancer. Among them, macrophage metalloelastase, MMP-12, has emerged as a particularly intriguing enzyme with both tumor-promoting and tumor-suppressive functions. Predominantly expressed by tumor-associated macrophages, MMP-12 occupies a unique position at the interface of proteolysis, inflammation, and immune regulation within the tumor microenvironment. Accumulating evidence from experimental models and clinical studies demonstrates that MMP-12 can exert potent anti-tumorigenic effects, primarily through inhibition of angiogenesis. Mechanistically, MMP-12 generates angiostatin and other anti-angiogenic fragments, suppresses vascular endothelial growth factor signaling, and reduces tumor vascularization, thereby limiting tumor growth and metastatic expansion. In several cancer types, including lung, colorectal, and hepatocellular carcinoma, elevated MMP-12 expression has been associated with reduced tumor progression and improved patient outcomes. Conversely, MMP-12 can also promote tumor progression through extracellular matrix remodeling, facilitation of invasion, and modulation of inflammatory pathways, particularly in environments characterized by chronic inflammation or immunosuppressive macrophage phenotypes. These seemingly contradictory roles are governed by multiple context-dependent factors, including macrophage polarization, tumor type, disease stage, and microenvironmental cues such as hypoxia and cytokine signaling. In this review, we comprehensively examine the molecular regulation, functional mechanisms, and clinical relevance of MMP-12 in cancer. We highlight the dualistic nature of MMP-12 activity and discuss its implications for therapeutic strategies, emphasizing the need for selective and context-aware targeting approaches rather than broad inhibition of MMP activity. Full article

Cancer remains a leading cause of global mortality, entailing the exploration of novel therapeutic agents from natural sources. This study evaluated the in vitro anti-cancer potential of essential oils (EOs) extracted from the needles of Pinus sylvestris L. (Scots pine) and Picea abies (L.) H. Karst. (Norway spruce). GC–MS analysis revealed that both EOs are rich in monoterpenes; the primary constituents were α-pinene (35.27%) for Pinus sylvestris sylvestris EO (Pinus EO) and β-pinene (31.40%) for Picea abies EO (Picea EO). Cell viability assay (Alamar Blue) demonstrated that both EOs exert a dose-dependent cytotoxic effect across all tested malignant lines: melanoma (A375), colorectal adenocarcinoma (HT-29), and pancreatic adenocarcinoma (PANC-1). Notably, Pinus EO consistently displayed higher potency toward cancer cells when compared with normal keratinocytes (HaCaT), with the highest selectivity noticed in HT-29 cells. Immunofluorescence analysis revealed morphological changes consistent with apoptosis, such as nuclear condensation, DNA fragmentation, and the disruption of the β-actin cytoskeleton. High-resolution respirometry indicated that the EOs increase LEAK respiration, while also significantly reducing the oxidative phosphorylation (OXPHOS) efficiency. Furthermore, network pharmacology and molecular docking predicted EP300 as a common hub target for both EOs, with β-caryophyllene showing the most favourable predicted binding affinity among the investigated constituents. Overall, these preliminary in vitro and in silico findings support the further investigation of Pinus EO and Picea EO as potential candidates for the development of future adjuvant strategies in cancer therapy. Full article

Pancreatic ductal adenocarcinoma (PDAC) is characterized by poor clinical outcomes and limited responsiveness to conventional treatments. Beyond delayed diagnosis, its high mortality is linked to limited treatment choices and resistance to chemotherapy. Neoplastic cells characterized by stem-like features and epithelial–mesenchymal transition (EMT) activation are crucial drivers of drug resistance and metastatic progression. Consequently, targeting these cellular programs could represent a promising therapeutic strategy for PDAC. N-acetyl-L-aspartic acid (NAA) is an endogenous metabolite, mainly localized in the central nervous system, where it facilitates acetate storage for lipid metabolism. Previous studies established its antineoplastic effect in neuroblastoma, promoting a more differentiated phenotype of cancer cells. Here we investigated the effects of NAA on BxPC-3 pancreatic cancer cells using both 2D and 3D models. NAA treatment induced a dose-dependent reduction in cell proliferation and led to a significant downregulation of stemness-associated surface markers, with concomitant upregulation of E-cadherin. Furthermore, NAA significantly enhanced cellular radiosensitization with a reduction in caveolin-1 and increased efficacy of gemcitabine in PDAC cells. Collectively, these results confirmed the anticancer activity of NAA and provide a rationale for further investigation of its synergistic effects with radiotherapy to yield better PDAC treatments. Full article

Background: Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, with lymph node metastasis (LNM) being a key predictor of recurrence and poor prognosis. Preoperative detection of LNM remains challenging due to the limitations of imaging modalities, leading to inadequate surgical resection in 20–30% of patients. While immune checkpoint molecules have been implicated in PTC progression, the heterogeneity of CD8⁺ T cell exhaustion subsets and their specific association with LNM remain poorly defined. In this study, we aimed to perform an exploratory characterization of the distinct immune landscape of PTC prone to LNM, with a focus on terminal immune exhaustion, in order to generate hypotheses for improved risk stratification and therapeutic strategies. Methods: Fresh PTC tissues from 40 patients (22 LNM-positive and 18 LNM-negative) were analyzed via flow cytometry (FCM) to quantify immune cell subsets, inflammatory cytokines, and chemokines. Immunohistochemistry (IHC) validated CD45⁺ immune cell infiltration. Transcriptomic and clinical data from 448 PTC patients in The Cancer Genome Atlas (TCGA-PTC) cohort were used for bioinformatic analysis consistent with the observed phenotype, including Gene Set Variation Analysis (GSVA) of terminal exhaustion gene signatures. Results: LNM-positive PTC exhibited a unique inflammatory milieu with significantly elevated IL-6, IL-1ra, CCL5, and IL-9 levels (all p < 0.05) in tumor interstitial fluid. FCM analysis revealed that LNM-positive PTC had increased infiltration of total CD45⁺ immune cells, CD3⁺ T cells, and CD3⁺CD8⁺ T cells (all p < 0.05). Critically, terminally exhausted PD-1^hiTIM-3⁺ CD8⁺ T cells were significantly enriched in LNM-positive PTC (p = 0.022) and positively correlated with extrathyroidal extension (p = 0.044). Additionally, LNM risk was associated with increased CD4⁺ regulatory T (Treg) cell frequency (p = 0.023) and elevated CTLA-4 expression on CD4⁺ T cells (p = 0.047). In TCGA-PTC validation, the terminal exhaustion gene signature was predominantly enriched in LNM-positive (p < 0.0001) and advanced-stage PTC (p < 0.001) and strongly correlated with BRAF mutation (predominantly V600E) (p < 0.0001)—the most common oncogenic driver in aggressive PTC. Conclusions: Our findings suggest a terminal immune exhaustion phenotype (characterized by PD-1^hiTIM-3⁺ CD8⁺ T cells and Treg enrichment) as a potential key feature associated with LNM-prone PTC. This phenotype shows consistency across clinical samples and TCGA datasets, linking BRAF mutation (predominantly V600E) to immune suppression and metastatic potential. These insights provide a novel exploratory immune-based biomarker for LNM risk stratification and support the potential of combining anti-PD-1/TIM-3 therapy with BRAF inhibitors for high-risk PTC, which should be confirmed in future studies. Full article

Cancer is still one of the major causes of death globally. While there are many cancer therapies, they often come with significant adverse effects and limitations. A lot of studies have shown that using natural products can improve the efficacy of conventional therapies and decrease their toxicity. Natural products and their derivatives encompassing unmodified molecules, semi-synthetic analogs, and synthetic structures featuring natural pharmacophores, represent a major foundation for approved anticancer agents. Phenolic compounds are a large family of naturally occurring compounds found in plants and have attracted a lot of attention for their potential anticancer properties. Preclinical studies have shown that phenolic compounds have anticancer activity through different mechanisms, mainly by modulating inflammation, which plays a critical role in cancer development. Inflammatory processes in cancer involve complex molecular mechanisms regulated by both oncogenic and tumor-suppressing transcription factors. This review focuses on how phenolic compounds regulate transcription factors, such as nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), and signal transducer and activator of transcription 3 (STAT3), which are critical in cancer-related gene expression, ultimately leading to the inhibition of cancer cell proliferation, invasion, and metastasis. Furthermore, phenolic compounds have been shown to synergize with conventional anticancer drugs, enhancing their efficacy and reducing side effects. This review investigates the role of phenolic compounds in regulating transcription factors in cancer animal models, highlighting both the therapeutic potential and limitations of these compounds in cancer prevention and treatment. Full article

Background/Objectives: Oxidative stress, chronic inflammation, disrupted apoptosis, and altered autophagy are biological processes implicated in colorectal tumor development. Morin is a plant-derived flavonoid with antioxidant and anti-inflammatory properties, but its limited solubility and bioavailability may limit its biological activity. This study evaluated the effects of free morin and morin-loaded liposomes (MOR-Lips) on 1,2-dimethylhydrazine (DMH)-associated colonic biochemical, molecular, and histopathological alterations in rats. Methods: Rats were randomly assigned to six groups—vehicle control, MOR, MOR-Lips, DMH, DMH + MOR, and DMH + MOR-Lips—and treated for 10 weeks. Serum and colonic tissues were evaluated for cancer-associated biomarkers (CEA, CA19-9, CA125, HMG-CoA reductase), oxidative stress and antioxidant indices, nitrosative and oxidative DNA-damage markers (MDA, NO, 8-OHdG), inflammatory mediators (TLR4/NF-κB/COX-2, cytokines, MPO), proliferative indices (Ki-67, PCNA), apoptotic and autophagy-related regulators (Bax, caspase-3, p53, cytochrome c, BCL-2, p-AKT, LC3-II, Beclin-1, p62), and histopathological and immunohistochemical changes. Results: DMH exposure was associated with increased CEA, CA19-9, CA125, HMG-CoA reductase, MDA, NO, 8-OHdG, TLR4/NF-κB/COX-2, cytokines, MPO, Ki-67, and PCNA. DMH also reduced NRF2/HO-1 signaling and antioxidant defenses, shifted apoptosis-related markers toward a pro-survival profile, altered autophagy-related markers, and produced marked colonic histopathological abnormalities. Both free MOR and MOR-Lips attenuated several of these DMH-associated alterations, with MOR-Lips generally producing greater effects than free MOR. MOR-LIP treatment was associated with restoration of antioxidant marker profiles, reduced levels of inflammatory and proliferative markers, a shift toward a pro-apoptotic marker profile, partial normalization of autophagy-related markers, and improved colonic histopathological appearance. Conclusions: In DMH-exposed rats, MOR-Lips were associated with more favorable redox, inflammatory, proliferative, apoptosis-related, autophagy-related, and histopathological profiles than free MOR. These findings support further investigation of MOR-Lips as a formulation strategy for improving the biological activity of morin. Because quantitative preneoplastic and neoplastic endpoints were not measured, the results do not establish inhibition of colorectal carcinogenesis or chemopreventive efficacy. Full article

Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a dose-limiting complication of paclitaxel (PTX) therapy, for which effective treatments are still lacking. This study evaluated the neuroprotective potential of Thymoquinone (TQ), a bioactive derivative of Nigella sativa, in mitigating chronic PTX-induced neurotoxicity without compromising antineoplastic activity. We first performed in vitro experiments using Sprague–Dawley rat embryonic (E15) Dorsal Root Ganglia (DRG) (Envigo Laboratory (Udine, Italy))to assess neurotoxicity through neurite outgrowth evaluation. To investigate the molecular mechanisms underlying TQ’s putative neuroprotective mechanisms, SIRT1 protein expression was additionally evaluated by western blot, while MCF-7 and MDA-MB-231 breast cancer cells were used to monitor cytotoxicity via MTT assay. We then moved to in vivo experiments, in which chronic neuropathy was induced in rats using PTX (10 mg/kg, i.v., weekly for 4 weeks). TQ was co-administered orally (5–10 mg/kg/day). The effects of TQ on peripheral neuropathy were assessed through behavioral testing, neurophysiological assessments, and histological analysis of Intraepidermal Nerve Fibre density (IENF), DRG and peripheral nerves. In vitro, TQ (5 μM) significantly attenuated PTX-induced neurite shortening at 24 h; TQ co-treatment fully prevented PTX-induced SIRT1 downregulation in embryonic DRG neurons and did not compromise PTX cytotoxicity in MCF-7 cells, while significantly potentiating it in MDA-MB-231 triple-negative breast cancer cells. In vivo results demonstrated that PTX-treated animals exhibited mild erythroid myelosuppression at the end of treatment. Regarding efficacy, TQ consistently prevented PTX-induced mechanical allodynia throughout the treatment period, and TQ (10 mg/kg) transiently mitigated IENF depletion at mid-treatment; however, no improvement in neurophysiological parameters or peripheral nerve morphology was observed at either time point. Collectively, these findings suggest that, under conditions of chronic PTX exposure, TQ exerts a predominantly analgesic effect in vivo, without conferring meaningful structural neuroprotection against PTX-induced peripheral nerve degeneration. Full article

Glycyrrhiza glabra is an herbaceous plant native to Eurasia, living in mild climates, and spread worldwide. Liquorice serves as a vital resource for human health, used as medicinal plants in feed and food, with anti-inflammatory and anticancer properties. To the best of our knowledge, no genetic studies on Italian populations of this species have been reported so far. This study investigated for the first time the genetics of the Mediterranean G. glabra samples found in small natural meadows in Agrigento and Trapani provinces (Sicily, Italy). To assess possible genetic differences among samples, two molecular markers were employed, ribosomal DNA-Internal Transcribed Spacer (rDNA-ITS) regions and Inter-Simple Sequence Repeats (ISSRs), both widely used for evaluating intra- and interspecific variability. Partial sequencing of the rDNA-ITS region was performed on five samples collected from two distinct locations in Agrigento and Trapani provinces, revealing complete sequence identity among them. ISSR analysis further confirmed the genetic conservation of samples. We also compared, by multiple alignment and phylogenetic analysis, the Sicilian rDNA/ITS sequences with G. glabra sequences coming from other countries, and with other species of Glycyrrhiza such as G. uralensis, G. inflata, G. aspera, G. echinata, and G. pallidiflora. The results revealed a high similarity among all analyzed sequences. Studying the genetic diversity of liquorice is important in preserving its medicinal properties, supporting plant conservation programs, and in expanding its applications in the healthcare field. Full article

Background: Triple-negative breast cancer (TNBC) remains a major cause of cancer mortality due to its aggressive behavior, metabolic adaptability, and high therapeutic resistance. Extracellular vesicles (EVs) within the tumor microenvironment contribute to tumor progression and metastasis by transferring pro-tumorigenic cargo. While conventional Tumor Treating Fields use high-frequency alternating fields to disrupt mitosis, low-energy triple-frequency bioelectromagnetic approaches remain poorly characterized. Methods: We evaluated a device–drug strategy combining triple-frequency low-intensity electromagnetic stimulation (EMS2: 396 Hz, 285 Hz, 528 Hz) with the pleiotropic drug Fingolimod (FTY720). Treatments were tested in MDA-MB-231 and ARM-G breast cancer cells, with Paclitaxel as a positive control. Cell proliferation was assessed by MTS assay, and extracellular vesicles were isolated following individual and combination treatments. Quantitative LC-MS/MS proteomics was used to characterize treatment-induced changes in EVs cargo. Results: EMS2 reduced proliferation in both cell lines and produced morphological changes consistent with altered cell-cycle progression. EMS2 alone triggered adaptive metabolic responses, whereas combination with Fingolimod suppressed these compensatory signatures. EVs proteomics revealed combination-specific alterations associated with mitochondrial stress, ER stress, NF-κB suppression, and autophagy-associated pathways. The combination also reduced levels of metastasis- and stroma-associated proteins, including Mitogen-Activated Protein Kinase 12 (MAPK12) and collagen-associated ECM components (Collagen Type I Alpha 1 Chain (COL1A1), Collagen Type VI Alpha 1 Chain (COL6A1), Collagen Type VI Alpha 3 Chain (COL6A3), and Matrilin 3 (MATN3)) in EVs. Bliss independence analysis identified a subset of metastasis-associated proteins suppressed in EVs beyond the level predicted by an additive model, an exploratory finding that will require further validation with dose–response and functional assays. Conclusions: Combined triple-frequency EMS2 and Fingolimod treatment altered the extracellular vesicle proteome, inducing signatures consistent with mitochondrial and endoplasmic reticulum stress, metabolic disruption, and reduced levels of metastasis-associated and stromal/ECM remodeling proteins, along with reduced proliferation. These findings suggest a coordinated anti-cancer effect of this tunable device–drug strategy, warranting further functional and in vivo validation to confirm therapeutic potential. Full article

Graphitic carbon nitrides (g-C₃N₄) are well-known fluorescent nanosheets that are photoactive under the UV–visible light range and could generate reactive oxygen species (ROS) upon appropriate light exposure. Therefore, these materials are generally favored in diagnostic applications for bioimaging and light-activated treatments simultaneously, e.g., theranostic applications in cancer treatments. Here, the natural polymer, hyaluronic acid (HA), was physically crosslinked with trivalent metal ions such as Gd(III) or Fe(III) ions in the presence of boron (B)- or sulfur (S)-doped graphitic carbon nitride (g-C₃N₄) nanosheets to attain spherical light-sensitive g-C₃N₄@HA-M(III) (M: G(III) or Fe(III) ions) composite microparticles. The g-C₃N₄@HA-M(III) particles were in the 0.5–20 μm size range, which is injectable for possible intravenous administration. No significant toxicity was determined for g-C₃N₄@HA-Gd(III) particles up to 500 μg/mL concentration on L929 fibroblast cells; for example, g-C₃N₄@HA-Fe(III) particles could be used in vivo applications safely up to 100 μg/mL concentration with no toxicity. The g-C₃N₄-based materials exhibited strong fluorescence at λ_ex 380 nm, and S-doped g-C₃N₄@HA-Gd(III) particles provided the highest emission intensity for possible cell imaging applications as a diagnostic tool material. Especially, S-doped g-C₃N₄@HA-M(III) particles delivered photoinduced anticancer activity on SKMEL 30 skin cancer cells after 30 min of UV-A treatment at 6.88 mW/cm² irradiance and 12.38 J/cm fluence via the reactive oxygen species (ROS) production capability. In addition to the targeting ability of HA-M(III) particles, the photoinduced anticancer activity of g-C₃N₄@HA-M(III) particles, e.g., on SKMEL 30 melanoma cells, offer great alternatives to toxic chemo- or radiotherapy. Furthermore, HA-Gd(III)-based particles show the highest signal intensity with better proton relaxation times and the highest proton longitudinal relaxivity. Overall, HA-Gd/Fe(III) particles with heteroatom-doped g-C₃N₄ revealed excellent assets with enhanced MRI capabilities in addition to specific targeted cancer treatments and photoinduced therapy for multifaceted theranostic applications. Full article

Cancer nanomedicine has generated extensive preclinical evidence of improved drug delivery, pharmacokinetics, and tolerability, yet its clinical impact has often remained modest. This narrative review examines the interconnected biological, pharmacokinetic, manufacturing, regulatory, and clinical factors underlying this translational paradox. A structured literature search was conducted primarily in PubMed and Google Scholar, focusing on studies published between 2022 and 2026 while retaining seminal earlier reports. Major biological barriers include protein corona formation, mononuclear phagocyte system clearance, heterogeneous enhanced permeability and retention, complex tumor microenvironments, and intratumoral heterogeneity. These factors limit circulation, tumor accumulation, tissue penetration, drug release, and interpatient reproducibility. Translation is further constrained by off-target accumulation, uncertain long-term toxicity, non-standardized experimental methods, batch-to-batch variability, scale-up challenges, and fragmented regulatory pathways. Clinical experience shows that successful products are dominated by relatively established platforms and reformulations of known anticancer agents, whereas many actively targeted or structurally complex systems have failed to demonstrate sufficient efficacy or safety. Future progress will require mechanism-driven design, human-relevant preclinical models, harmonized characterization, quality-by-design manufacturing, early regulatory integration, biomarker-guided patient selection, and adaptive clinical trials. Aligning nanoparticle engineering with biological and clinical realities is essential for achieving meaningful patient benefit. Full article

Background: The fibrous tumor extracellular matrix (ECM), driven by cancer-associated fibroblasts (CAFs), forms a physical barrier against drugs and immune cells, yet direct CAF elimination risks promoting metastasis. Methods: In this study, we developed a locally injectable hydrogel based on synergistic dynamic covalent crosslinking (imine and boronate ester bonds), enabling instant gelation, shear thinning, and dual-pH/ROS-responsive degradation. Two types of drug-loaded nanoparticles (NPs), coated with homotypic cell membranes, were incorporated into this hydrogel. In the acidic, reactive oxygen species (ROS)-rich tumor microenvironment (TME), the system responsively releases the antifibrotic drug SIS3 to reprogram CAFs while simultaneously delivering doxorubicin (DOX) specifically to tumor cells. Biological effects were evaluated in vitro using cell cultures and in vivo in mouse models. Results: This dynamic hydrogel-based co-delivery system effectively reprograms CAFs, reduces tumor mechanical stress, breaks the fibrotic barrier, and promotes the deep infiltration of chemotherapeutics and immune cells, thereby enhancing the efficacy of chemotherapy. Conclusions: This injectable pH/ROS-responsive dynamic covalent hydrogel, loaded with CAF- and cancer cell-targeting NPs, remodels the TME, enhances drug and immune cell penetration, and offers a promising biomaterial-based strategy for cervical cancer treatment. Full article

Population aging has intensified the search for natural compounds capable of promoting healthy aging and preventing age-related diseases. Among medicinal plants, species of the genus Crataegus (hawthorn) have attracted increasing attention because of their rich phytochemical composition and broad spectrum of biological activities. This review summarizes and critically evaluates current evidence on the geroprotective potential of Crataegus species, integrating data from phytochemical, pharmacological, and mechanistic studies. Particular attention is given to the major bioactive constituents of Crataegus, including flavonoids, oligomeric proanthocyanidins, phenolic acids, and triterpenoids, which exhibit antioxidant, anti-inflammatory, cardioprotective, neuroprotective, metabolic, and anticancer properties. We discuss the growing evidence that these phytochemicals target multiple hallmarks of aging by modulating oxidative stress, chronic low-grade inflammation (inflammaging), mitochondrial dysfunction, cellular senescence, and the senescence-associated secretory phenotype (SASP). Their biological effects are mediated through key signaling pathways involved in cellular homeostasis and longevity, including Nrf2/ARE, NF-κB, PI3K/Akt/mTOR, AMPK, and SIRT1. The review also critically examines findings from in vitro, in vivo, and available clinical studies, highlighting both the therapeutic potential and current limitations of Crataegus-based interventions for age-related disorders. Although preclinical evidence strongly supports the multi-target geroprotective properties of Crataegus species, clinical validation remains limited. Overall, Crataegus represents a promising source of natural geroprotective agents with the potential to promote healthy aging through the modulation of multiple aging-related molecular pathways. Future well-designed clinical studies are essential to establish their efficacy, safety, optimal dosage, and long-term therapeutic value in humans. Full article

Vernonia calvoana (VC), a commonly used medicinal plant in West Africa, has been shown by our research team to inhibit the proliferation of OVCAR-3 ovarian cancer cells through mechanisms involving oxidative stress, DNA damage, and S-phase cell cycle arrest. The objective of the current study was to elucidate the intrinsic apoptotic mechanisms triggered by VC fraction seven (VCF7). OVCAR-3 cells were treated with VCF7 (0, 8, 16, and 32 μg/mL) for a duration of 48 h. Apoptosis was assessed using Annexin V/Propidium Iodide (PI) staining followed by flow cytometry analysis. Mitochondrial membrane potential (ΔΨm) was assessed through JC-1 staining and confocal microscopy, while chromatin condensation was analyzed using DAPI staining. DNA fragmentation was examined by agarose gel electrophoresis. Caspase 3 activity was measured using flow cytometry. Protein expression levels of p53, Bcl-2, cytochrome c, caspase-9, and caspase-3 were determined by Western blot analysis, and mRNA expression levels of p53 and Bcl-2 were evaluated using qRT-PCR. VCF7 induced apoptosis in a concentration-dependent manner. Analysis using Annexin V/PI indicated an increase in apoptotic cell populations from 10.5% to 30%, along with a rise in necrotic cells from 7% to 50% across treatment concentrations. A modest, concentration-associated decrease in mitochondrial membrane potential was recorded (0.96-, 0.88-, and 0.85-fold at 8, 16, and 32 μg/mL, respectively; p < 0.05). DAPI staining validated the concentration-dependent chromatin condensation and nuclear fragmentation. The analysis of DNA fragmentation showed progressive internucleosomal degradation, appearing as a smear pattern with distinct fragments at elevated concentrations, indicative of concurrent apoptotic and necrotic cell death. The activation of caspase-3 reached a peak of 28% at 16 μg/mL. Western blot analysis indicated an upregulation of p53, a downregulation of Bcl-2, an increase in total cytochrome c protein levels, and an increased expression of caspase-9 and caspase-3 in a concentration-dependent manner. These findings were corroborated at the transcriptional level by qRT-PCR, which showed increased p53 mRNA and decreased Bcl-2 mRNA expression. Taken together, these results underscore the potential of VCF7 as a promising plant-derived anticancer agent and support the need for further preclinical and clinical studies in ovarian cancer. Full article

Doxorubicin (DOX) is an antineoplastic agent commonly used in cancer therapy that is known for its testicular toxicity. DOX-induced testicular injury involves inflammation, reactive oxygen species, and oxidative stress. Centella asiatica exhibits anti-inflammatory and antioxidant properties. The present experimental study aimed to determine the potential protective efficacy of Centella asiatica in a rat model of doxorubicin-induced testicular toxicity. Rats were randomly assigned to four groups: healthy control (HC), CA, DOX, and CA + DOX (CADX). An oral dose of 200 mg/kg Centella asiatica was administered to the CA and CADX groups. The HC and DOX groups received saline. One hour later, DOX (7.5 mg/kg) was intraperitoneally injected into the DOX and CADX groups on days 1, 4, and 7. Centella asiatica markedly attenuated the DOX-induced increase in malondialdehyde, nitric oxide, and pro-inflammatory cytokine levels, while preventing the decrease in superoxide dismutase activity in testicular tissue (p < 0.001). Centella asiatica reduced the severity of DOX-induced morphological damage in testicular tissue (p < 0.05). Moreover, it partially restored reproductive hormone function. In conclusion, Centella asiatica demonstrates significant potential in mitigating DOX-induced oxidative damage, attenuating testicular injury and preserving the functional integrity of the male reproductive system. Full article