Search Results (387)

Background/Objectives: Glucocorticoids, including dexamethasone (DEX), are known to demonstrate anti-inflammatory activity, suppress steroidogenesis, and mitigate the adverse effects of chemotherapy. They are therefore widely employed for managing solid malignancies. Emerging evidence indicates that DEX modulates both systemic and local renin–angiotensin system (RAS) activity, including genomic signaling via the glucocorticoid receptor (GR). Methods: DEX-dependent transcriptional responses for the angiotensin receptor genes (AGTR1, AGTR2, MAS1, and LNPEP) were evaluated in ovarian (SKOV3, KURAMOCHI) and prostate (DU-145, PC3) cancer cell lines. The cells were cultured under different serum conditions to determine the influence of nutrient availability on tumor progression. Results: DEX demonstrated distinct mechanisms of action between the ovarian and prostate cancer models. It was found to promote cancer cell survival through tissue-specific modulation of metabolic activity, clonogenic capacity, cell cycle distribution, and apoptotic responses. These effects were accompanied by condition-dependent alterations in angiotensin receptor gene expression. Hence, DEX may mediate the remodeling of local RAS signaling, which may be significant in overall survival and disease-free survival. The findings also indicate a previously-unreported NR3C1–LNPEP correlation, which was consistently observed across in vitro systems and patient datasets, in both ovarian- and prostate-derived cancer models. Conclusions: DEX appears to exert context-dependent regulation of RAS-associated gene networks in ovarian and prostate cancer, suggesting a role in tumor adaptive responses and potentially in therapeutic contexts. Full article

Bitter Melon Leaf Extract (BMLE) possesses potential anticancer and anti-inflammatory properties; however, conventional extraction methods restrict phytochemical yield and bioactivity. Here, we optimized extraction using High-Pressure Processing (HPP) with Box–Behnken Design (BBD) and Response Surface Methodology (RSM). The optimized extract (O-BMLE) demonstrated significantly higher total flavonoid content (27.7 vs. 8.7 mg RE/g) and FRAP antioxidant capacity (96.5 vs. 71.2 μmol TE/g) compared to conventional BMLE. Additionally, O-BMLE exhibited enhanced cytotoxicity (A549 IC₅₀: 58.7 vs. 147 μg/mL) and selectivity (SI: 5.03 vs. 2.60) against A549, HepG2, and SKOV3 cancer cells while showing minimal effects on 3T3-L1 fibroblasts. In LPS-stimulated RAW264.7 macrophages, O-BMLE selectively inhibited JNK phosphorylation without affecting NF-κB phosphorylation, resulting in suppression of iNOS, COX-2, IL-1β, IL-6, and TNF-α expression as well as nitric oxide production. HPLC analysis revealed equivalent momordicine-I levels (~28 mg/g) between extracts. In contrast, HPLC-qTOF-MS profiling revealed that O-BMLE was enriched in stearidonic acid (66% increase in relative abundance), 4-hydroxybenzoic acid (19.5%), monolinolenin, 6-gingerol, and pedunculoside, which are compounds linked to JNK inhibition, antioxidant activity, and cytokine suppression. These results indicate that HPP-BBD/RSM optimization selectively modifies the bitter melon leaf metabolome, thereby enhancing anticancer and anti-inflammatory activities independently of momordicine-I content alone. O-BMLE may therefore serve as a promising candidate for the development of functional foods and nutraceuticals targeting inflammation-associated cancers. Full article

Pharmacophore hybridization is a well-established strategy for developing novel anticancer agents with improved biological profiles. In this study, a new series of (E)-4-(4-acrylamidophenoxy)-N-methylpicolinamide derivatives has been rationally designed by hybridizing key structural features of sorafenib with cinnamide pharmacophores and subsequently synthesized. The antiproliferative activities of the synthesized compounds were evaluated against a panel of human cancer cell lines, including A549 (lung), DU-145 (prostate), SKOV3 (ovarian), and HepG2 (liver), along with non-cancerous Hek293T cells. In comparison with the standard drug sorafenib, most of the (E)-4-(4-acrylamidophenoxy)-N-methylpicolinamides demonstrated significant antiproliferative activity, with specificity toward the HepG2 (liver cancer) cell line, and no effect on the noncancerous cells (Hek293T). Among them, compound 5f, the derivative containing a trifluoromethyl-substituted cinnamoyl moiety was identified as the lead candidate, exhibiting an IC₅₀ of 5.3 µM towards HepG2 (liver) cancer cells, comparable to the reference drug sorafenib. Enzyme inhibition studies showed that compound 5f inhibited both b-Raf and VEGFR-2 with IC₅₀ values of 1.45 and 0.37 µM, respectively. Furthermore, compound 5f suppressed angiogenesis in vitro and in vivo, as evidenced by the tube formation assay using HUVECs and in transgenic zebrafish Tg(fli1a:EGFP) models, respectively. Mechanistic studies indicated that compound 5f induced apoptosis in HepG2 cells through mitochondrial membrane depolarization and increased ROS generation. Molecular docking studies supported experimental findings and showed that 5f can interact with catalytically active residues via hydrogen-bonding interactions. Overall, these results highlight the potential of compound 5f as a promising dual target therapeutic lead with dual direct anticancer and antiangiogenic properties. Full article

The fusion of heterocycles onto an anthraquinone scaffold represents a promising strategy to optimize anticancer activity. This study has the aim to synthesize and characterize novel anthra[1,2-b]furan compounds based on the natural product aloe-emodin. Six novel anthra[1,2-b]furans bearing phenyl, n-hexane, and methoxy carbonyl substituents were synthesized starting from aloe-emodin. The synthetic route employed involved acetyl protection of aloe-emodin, electrophilic aromatic halogenation, subsequent Castro–Stephens coupling, spontaneous intramolecular cyclization, and deprotection of hydroxyl groups. These newly synthesized compounds were evaluated for their cytotoxic activity against various cancer cell lines, including lung adenocarcinoma (A5492), colorectal carcinoma (HCT116), hepatocellular carcinoma (HepG2), ovarian cancer (Skov3), and breast cancer (MCF-7), using the CCK8 assay. The anthra[1,2-b]furan derivative 10c, which contains a methoxy carbonyl group, demonstrated excellent potency against lung (A549) and breast (MCF-7) cancer cell lines, with IC₅₀ values of 0.49 and 2.91 µM, respectively. This preliminary cytotoxic finding shows compound 10c as a promising hit for further investigations towards a promising lead compound. Full article

Background: Recurrence poses a major challenge in epithelial ovarian cancer (EOC), often occurring despite optimal first-line therapy. Dormant cancer cells are believed to play a key role, yet the mechanisms driving their reactivation remain unclear. This study examined whether exosomes released by normal peritoneal mesothelial cells (PMCs) and fibroblasts (PFBs) undergoing iatrogenic senescence after carboplatin and paclitaxel exposure contribute to EOC recurrence. Methods and Results: Senescent PMCs and PFBs secreted markedly more exosomes, identified by CD9, CD63, and CD81, compared with young cells. Exosomes from both cell types more effectively reactivated dormant EOC cells (pEOCs, A2780, OVCAR-3, SKOV-3) than non-exosomal medium constituents. Importantly, senescent PMC-derived exosomes most strongly reactivated pEOCs and SKOV-3, whereas those from senescent PFBs exerted greater effects on pEOCs, OVCAR-3, and SKOV-3. Kinetic studies of exosome internalization revealed that this process was generally more efficient in the presence of exosomes derived from senescent cells compared with those from young donor cells. Compositional analysis revealed distinct profiles between young and senescent exosomes compared in two variants: young PMCs/senescent PMCs and young PFBs/senescent PFBS. Senescent PMC exosomes displayed reduced miR-210-3p, miR-409-3p, and miR-421, alongside elevated MMP1, MMP3, and VEGF, while senescent PFB exosomes showed increased amphiregulin and osteopontin but lower MMP1, MMP3, TIMP1, bFGF, VEGF, and HGF. Functionally, senescent PMC exosomes enhanced pEOC migration, invasion, and spheroid formation, and induced the expression of CCL11 and ABCB1. Senescent PFB exosomes promoted migration and upregulated CCL11, TGF-β1, BIRC5, and CHEK1. Conclusions: These findings suggest that therapy-induced senescence in peritoneal cells may contribute to EOC recurrence by reactivating dormant tumor cells through exosomal signaling. Full article

Background/Objectives: Peritoneal micrometastases (micromets) remain a major barrier to durable cytoreduction in ovarian and other intra-abdominal cancers because lesions are difficult to visualize and are often resistant to systemic therapy. Liposomal doxorubicin (Dox) improves pharmacokinetics but can be limited by slow intratumoral release. Porphyrin-phospholipid (PoP) liposomes enable near-infrared light–triggered release of Dox (chemophototherapy (CPT)), creating an opportunity for intraoperative fluorescence-guided treatment planning and monitoring. Here, we evaluate a laparoscopic fluorescence imaging platform for quantifying light-triggered drug delivery. Methods: LC-Dox-PoP was applied to SCC2095sc and SKOV-3 cultures in 2D monolayers and 3D spheroid clusters. Dox fluorescence was quantified using a laparoscopic fluorescence imaging system over 1–9 μg/mL concentrations and compared with standard well-plate reader measurements. Porphyrin fluorescence was monitored to assess spheroid localization and photobleaching after activation light exposure. Results: For both cell lines, Dox fluorescence exhibited an approximate 4-fold increase at the maximum administered LC-Dox-PoP concentration, following a linear trend in both SCC2095sc and SKOV-3 cultures (R² = 0.97, 0.98 for 2D and R² = 0.98, 0.98 for spheroids). Laparoscope-derived fluorescence measurements agreed with well-plate reader measurements (R² = 0.89–0.96). Porphyrin fluorescence provided stronger complementary contrast for localizing spheroid constructs and decreased after activation light exposure, consistent with photobleaching during triggered release. Conclusions: These results support a quantitative imaging framework for fluorescence-guided monitoring of light-triggered liposomal drug release and may enable individualized CPT dosimetry for peritoneal micrometastases. Findings in SCC2095sc additionally suggest potential relevance of fluorescence-guided CPT for head and neck/oral cancer, where localized post-resection adjuvant treatment may improve control of residual disease. Full article

Background: Despite pharmacological advances, many cancer therapies provide only limited clinical benefits while often inducing significant toxicity. Therefore, the search for more effective and safer anticancer drugs remains an urgent priority. This study aimed to identify plant extracts from the Andalusian flora (Southern Spain) with selective anticancer potential. Methodology: A total of 67 extracts from 59 plant species were screened for selective cytotoxicity using A549 lung adenocarcinoma and HaCaT non-malignant cells. The most promising candidates, extracts from Thymelaea lanuginosa and Daphne oleoides, were further evaluated through fluorescence-based co-cultures, cell cycle analysis, and redox-mechanism assay. These extracts were also tested against a panel of cancer cells derived from different tissues (MDA-MB-231, T24, KATO-III, SK-OV-3, and MeWo). Results: Several extracts exhibited selective activity against A549 cancer cells, including extracts from Chamaeiris foetidissima (L.) Medik. (=Iris foetidissima L.), Daphne oleoides Schreb, Iberodes linifolia (L.) M. Serrano, R. Carbajal & S. Ortiz, Reseda media Lag., Saxifraga hirsuta L., Seseli montanum subsp. granatense (Willk.) C. Pardo, Thymelaea lanuginosa (Lam.), and Tordylium officinale L. The extracts from D. oleoides and T. lanuginosa were over 1000 times more active against lung cancer cells than non-malignant cells. These extracts induced a specific G1-phase arrest in A549 cells. Both extracts showed also selective activity against triple-negative breast cancer cells (MDA-MB-231) and bladder cancer cells (T24). Conclusions: These findings highlight Daphne and Thymelaea species as valuable sources for discovering novel selective anticancer agents. Future research should focus on bio-guided fractionation and in vivo validation to fully delineate their therapeutic potential. Full article

Complexes of colchicine, colchiceine, and 10-methylthiocolchicine with Li⁺, Na⁺, and K⁺ cations in the form of chlorides were synthesized and then subjected to spectral analysis, DFT theoretical studies, and molecular modeling. The values for water solubility and lipophilicity were also determined using various platforms; both factors are very important for determining the bioavailability of the tested compounds. These compounds were also tested for their fungicidal, herbicidal, insecticidal, and cytotoxic activities. Preliminary in silico studies showed that colchicine, colchiceine, 10-methylthio-colchicine, and their chloride complexes are inactive against selected fungi, weeds, and insects. Colchicine did not show antifungal properties in biological tests and was only active against Aureobasidium pullulans, as were its chloride complexes. The process of complexing colchiceine with metal cations in chloride salts significantly improved the antifungal potency against the selected species A. pullulans and Chaetomium globosum. The highest efficacy of colchiceine complexes was observed only against A. pullulans (MIC = 130 µg/mL) and Ch. globosum (MIC = 65 μg/mL). In contrast to the antifungal activity results, anticancer studies showed that 10-methylthiocolchicine complexes are more active against the SKOV-3 cell line (~IC50 = 2 nM) than colchicine or colchiceine. Molecular-modeling studies confirmed that lithium-coordinated compounds strongly stabilized the active ligand-tubulin complex, which may contribute to the observed cytotoxic activity. Full article

Background: Ovarian cancer (OC) is characterized by aggressive progression, high metastatic potential, and frequent resistance to conventional chemotherapy, highlighting the need for novel combination-based therapeutic strategies. Metformin has emerged as a promising antineoplastic agent; however, its efficacy may be enhanced through combination with bioactive compounds. This study aimed to investigate the antineoplastic effects of metformin in SKOV3 human OC cells and to evaluate whether these effects could be potentiated by boric acid (BA) and resveratrol, with particular emphasis on their modulatory impact on key inflammatory and tumor-associated biomarkers, including interleukin-17 (IL-17), nuclear factor kappa-B (NF-κB), and midkine (MDK). Methods: SKOV3 cells were treated with metformin, BA, and resveratrol as monotherapies or in combination. Cell viability was assessed using a colorimetric assay, while migratory capacity was evaluated by wound healing analysis. The expression levels of IL-17, NF-κB, and MDK were quantified in cell lysates, and p21 protein expression was analyzed by immunocytochemistry. Results: All treatments induced concentration- and time-dependent reductions in cell viability. Combination treatments, particularly metformin with boric acid or resveratrol, produced more pronounced inhibitory effects on cell survival and migration compared with single-agent treatments. Inflammatory and tumor-associated biomarkers, including IL-17, NF-κB, and MDK, were significantly modulated following treatment. Additionally, increased p21 expression was observed in treated cells, indicating enhanced cell cycle regulatory activity. Conclusions: These findings indicate that BA and resveratrol enhance the antineoplastic activity of metformin in SKOV3 OC cells by suppressing proliferative and migratory capacities and modulating inflammatory mediators such as IL-17, NF-κB, and MDK. However, since toxicity assessments in non-cancerous cells were not performed, the safety profile of this combination remains unclear and requires further investigation in non-cancerous models. Full article

Ovarian cancer remains a major cause of mortality in women aged 74 years and under. Dysregulation of the PI3K/AKT/mTOR and NFκB signaling pathways has been associated with poor outcomes and treatment resistance. This study evaluated three potential anticancer agents targeting these pathways: buparlisib (a pan-PI3K/mTORC1 inhibitor), SN32976 (a PI3K p110α inhibitor), and pterostilbene (a resveratrol analogue that downregulates PI3K/AKT and NFκB signaling). Their efficacy was tested in 3D collagen models of ovarian cancer, using SKOV3 and OVCAR8 cell lines, activated by tumor necrosis factor-alpha (TNFα) and lysophosphatidic acid (LPA). Using concentrations derived from 2D assays, viability, collagen gel sizes, secretion of interleukin 6/8 (IL-6/8) and signal pathway proteins were analyzed. All compounds were less effective in 3D models than in 2D cultures, with high cell viability maintained. TNFα and LPA did not significantly alter drug sensitivity, and collagen gel contraction was largely unaffected. While the compounds did not consistently change signaling protein levels, they generally reduced secretion of pro-inflammatory cytokines IL-6 and IL-8. Growth in 3D collagen gels conferred drug resistance on OVCAR8 but not SKOV3 models. Overall, these findings provide preclinical support for further investigation of SN32976 and pterostilbene in ovarian cancer models. Full article

Background/Objectives: Ovarian cancer remains a highly lethal malignancy, largely due to the development of therapeutic resistance, particularly in advanced disease. Combination strategies targeting complementary molecular pathways may enhance antitumor efficacy and help overcome resistance. The present study aimed to systematically evaluate the anticancer effects of the PARP1 inhibitor PJ34 and the natural polyphenol curcumin, administered alone and in combination, in platinum-sensitive and relatively platinum-resistant ovarian cancer models, with an emphasis on quantitative synergy assessment and functionally supported, hypothesis-generating mechanistic insight. Materials and Methods: Cell viability was evaluated using the MTT assay, and IC₅₀ values were derived from dose–response curves. Drug interactions were quantitatively analyzed using the Chou–Talalay method, including combination index (CI) and dose reduction index (DRI) calculations. Intracellular reactive oxygen species (ROS) levels were measured using DCFH-DA-based assays. Cell migration was assessed using scratch-wound assays. Apoptosis was evaluated using Annexin V/PI flow cytometry, caspase-3 activity assays, and quantitative real-time PCR (RT-qPCR) analysis of apoptosis-related genes (Bax, Bcl-2, Caspase-3, Caspase-9, and p53). To further validate the findings under physiologically relevant conditions, three-dimensional (3D) tumor spheroid models were employed, and ROS involvement was functionally interrogated using N-acetyl-L-cysteine (NAC) rescue experiments to assess ROS-associated contributions rather than direct causality. Results: PJ34 and curcumin each reduced cell viability in a dose-dependent manner, whereas their combination produced a synergistic antiproliferative effect with reduced IC₅₀ values. Synergism was particularly pronounced in relatively platinum-resistant SKOV-3 cells. Combination treatment significantly enhanced regulated apoptotic cell death, as demonstrated by increased apoptotic fractions, elevated caspase-3 activity, and an increased Bax/Bcl-2 ratio, with minimal necrosis. While PJ34 moderately increased intracellular ROS levels and curcumin reduced oxidative stress, the combination was associated with the normalization of ROS levels to near-control values. In 3D tumor spheroid models, combined treatment induced marked spheroid shrinkage, loss of structural integrity, and reduced viability, indicating a preservation of synergistic cytotoxic effects beyond two-dimensional (2D) conditions. NAC pretreatment partially attenuated, but did not fully rescue, the cytotoxic effects of the combination, indicating a ROS-associated, but not exclusively ROS-dependent, mechanism of action. In addition, the combination markedly inhibited cell migration in both ovarian cancer cell lines. Conclusions: This preclinical provides evidence that combined PARP1 inhibition and curcumin treatment can exert synergistic antitumor effects in ovarian cancer models, including relatively platinum-resistant disease, through the coordinated suppression of proliferation, induction of regulated apoptosis, and inhibition of migration. The integration of quantitative synergy analysis, 3D spheroid validation, and ROS-rescue experiments provides functionally supported, hypothesis-generating mechanistic insight and supports further evaluation of PARP inhibitor–curcumin combinations as a mechanistic proof-of-concept in advanced preclinical models. Full article

KRAS is frequently amplified or overexpressed in ovarian cancer and represents a potential therapeutic target for overcoming chemoresistance. We employed complementary approaches—CRISPR/Cas9 gene editing, Tet-ON inducible knockdown, polypurine reverse Hoogsteen hairpin (PPRH) oligonucleotides, and the pan-KRAS inhibitor BI2865—to investigate whether KRAS modulation enhances chemotherapeutic efficacy in ovarian cancer models. CRISPR-mediated KRAS knockdown in SKOV-3 cells dramatically altered three-dimensional spheroid morphology, reducing the average area six-fold, and significantly enhanced sensitivity to both cisplatin and paclitaxel in 3D cultures, where paclitaxel resistance was completely reversed. The Tet-ON system demonstrated dose-dependent chemosensitization with optimal effects at intermediate KRAS knockdown levels (~50–60%). PPRH oligonucleotides at sub-cytotoxic concentrations (50 nM) reduced cisplatin and paclitaxel IC₅₀ values by approximately 50% in 2D cultures. Pharmacological KRAS inhibition with BI2865 produced striking synergy with paclitaxel (several hundred-fold sensitizations in 2D; complete reversal of 3D resistance), and additive effects with cisplatin. In KRAS-amplified Kuramochi cells (representing high-grade serous ovarian carcinoma), BI2865 enhanced paclitaxel efficacy, despite greater baseline chemoresistance. These findings establish KRAS as a promising chemosensitization target in ovarian cancer, with particular potential for taxane-based combination therapies. Full article

This study aimed to elucidate the oncogenic role of FOXA1(forkhead box A1) in ovarian cancer and to evaluate its potential as both a therapeutic target and a diagnostic biomarker. We further investigated whether FOXA1 inhibition could enhance responsiveness to immune checkpoint blockade and overcome chemoresistance. A total of seventy-six ovarian tissue samples were analyzed, including nine normal, thirty-four benign, and thirty-three malignant specimens. IHC (immunohistochemistry) staining was performed to assess FOXA1 expression and its correlation with tumor stage. Functional studies were conducted using FOXA1 siRNA in SK-OV3 and HEYA8 cell lines. Changes in cell proliferation, migration, invasion, and wound-healing ability were evaluated following FOXA1 silencing. Quantitative RT-PCR was used to measure the expression of FOXA1 and EMT (epithelial–mesenchymal transition)-related genes. The effects of FOXA1 inhibition on sensitivity to carboplatin and the immune checkpoint inhibitor atezolizumab were also examined. IHC analysis revealed significant differences in FOXA1 expression among normal, benign, and malignant tissues, with levels correlating with tumor stage. FOXA1 silencing significantly reduced proliferation and decreased migration and invasion by 60–80%, accompanied by marked downregulation of EMT-related genes. Moreover, FOXA1 inhibition enhanced atezolizumab responsiveness and reduced carboplatin resistance in ovarian cancer cells. In summary, FOXA1 acts as an oncogenic driver in ovarian cancer, promoting proliferation, invasion, and EMT activation. Its overexpression correlates with disease progression, supporting its potential as a biomarker and therapeutic target. Targeting FOXA1 could enhance immunotherapy efficacy and help overcome chemoresistance in ovarian cancer. Full article

Benzoxaboroles have garnered significant interest for their therapeutic potential in various diseases. Among them, 7-propanamide benzoxaborole has served as a new and valuable chemotype for anti-cancer agents, although their definitive intracellular target(s) remains elusive. Herein, three-dimensional quantitative structure–activity relationship (3D-QSAR) was used to systematically investigate the structure–activity relationships (SAR) of a series of 7-propanamide benzoxaboroles. Comparative molecular field analysis (CoMFA, r² = 0.991, q² = 0.626) and comparative molecular similarity indices analysis (CoMSIA, r² = 0.964, q² = 0.605) revealed critical structural determinants of 7-propanamide benzoxaboroles for inhibition of the ovarian cancer cell (SKOV3) proliferation. Based on the guidance of the critical structural determinants, we designed a new benzoxaborole compound 42 with high predicted inhibition activity values. In vitro proliferation assessment showed that compound 42 exhibited superior inhibitory potency to lead compound 1 and comparable activity to compound 41. These findings indicated that the SAR of benzoxaborole compounds through 3D-QSAR can offer valuable theoretical insights for the structural optimization of new benzoxaboroles as anti-SKOV3 agents. Full article

Mitochondrial oxidative phosphorylation serves as a critical driving force in the progression of ovarian cancer. Recent studies have demonstrated that copper induces mitochondrial-dependent programmed cell death by directly binding to the thioacylated components of the tricarboxylic acid (TCA) cycle. The involvement of copper in OXPHOS complex IV, a rate-limiting step in the mitochondrial respiratory chain, suggests that the role of mitochondria in mediating copper-induced cell death can be further elucidated through the study of OXPHOS complex IV. The findings of this study indicate that the cuproptosis process in ovarian cancer, induced by Elesclomol, is associated with mitochondrial complex IV, with LRPPRC identified as a crucial factor. Following Elesclomol treatment of ovarian cancer cells, there was a notable increase in mitochondrial reactive oxygen species (ROS), a significant accumulation of the copper death marker protein DLAT, and a marked decrease in the lipoic acid synthesis-related protein FDX1. Furthermore, the expression levels of copper ion transporters ATP7B and CTR1, which are involved in the assembly and translation of complex IV, as well as the core subunit MTCO1 of complex IV, the copper chaperone protein SCO1, and the interacting protein LRPPRC, were significantly diminished. Inhibition of the IV-stabilizing protein LRPPRC in the ovarian cancer cell lines A2780 and SKOV3 through RNA interference resulted in increased sensitivity to Elesclomol. Concurrently, the expression levels of FDX1, LIAS, LIPT1, SCO1, and MTCO1 decreased significantly. These findings suggest that LRPPRC plays a role in inhibiting the expression of lipoic acid and copper chaperone proteins during Elesclomol-induced copper death in ovarian cancer. This inhibition collectively diminishes the expression and activity changes in complex IV, induces mitochondrial dysfunction, and promotes cuproptosis in ovarian cancer. This study further demonstrates that inhibiting the oxidative phosphorylation complex IV can enhance copper-induced cell death in ovarian cancer. Full article