Doxorubicin is a highly effective anticancer agent, but its clinical use is restricted by severe side effects, including atherosclerosis and cardiomyopathy. These complications are partly attributed to doxorubicin’s ability to induce endothelial-to-mesenchymal transition (EndMT) in vascular endothelial cells, a critical process in the initiation and progression of atherosclerosis and cardiomyopathy. GV1001, a multifunctional peptide with anti-inflammatory, anti-cancer, antioxidant, and anti-Alzheimer’s properties, has demonstrated inhibition of EndMT. We investigated whether GV1001 could counteract doxorubicin-induced EndMT in endothelial cells and prevent atherosclerosis in a mouse model. The results revealed that GV1001 significantly suppressed EndMT induced by doxorubicin, likely through its protective effects on mitochondria. By mitigating mitochondrial damage, GV1001 reduced the accumulation of mitochondrial and cellular reactive oxygen species (ROS), repressed the activation of nuclear factor kappa B (NF-κB), and reduced the production of proinflammatory cytokines in endothelial cells. Additionally, GV1001 reduced systemic and vascular inflammation, lipid accumulation, and monocyte/macrophage infiltration within arterial walls in mice. In conclusion, GV1001 appears to prevent doxorubicin-induced atherosclerosis by safeguarding vascular endothelial cells from mitochondrial dysfunction, inflammation, and phenotypic changes. These findings suggest the potential of GV1001 as a therapeutic agent to mitigate the long-term cardiovascular side effects associated with doxorubicin treatment in humans.

GV1001, a multifunctional peptide, has shown numerous biomedical activities, including antioxidant, anti-inflammatory, anti-Alzheimer’s, and anti-atherosclerotic effects, and protects mitochondria from cytotoxic agents. Cisplatin is a widely used chemotherapeutic agent against cancers, but its clinical utility is limited by nephrotoxicity driven by mitochondrial dysfunction in renal epithelial cells. Here, we investigated whether GV1001 protected against cisplatin-induced nephrotoxicity (CIN) in vivo and preserved mitochondrial integrity in human renal epithelial cells in vitro. In mice, GV1001 substantially mitigated CIN by significantly reducing histological damage, kidney injury marker expression, macrophage infiltration, endothelial-to-mesenchymal transition, inflammation, and apoptosis. In cultured renal epithelial cells, GV1001 maintained mitochondrial membrane potential, preserved ATP production, and prevented mitochondrial membrane peroxidation possibly by binding to cardiolipin. GV1001 also reduced the level of reactive oxygen species (ROS), suppressed cytochrome c release into the cytosol, and inhibited activation of apoptosis-related pathways elicited by cisplatin. Collectively, these findings demonstrated that GV1001 might protect kidney from cisplatin through maintaining mitochondrial structure and function and suppressing downstream injury cascades in renal epithelial cells. By directly targeting the mitochondrial mechanisms underlying cisplatin toxicity, GV1001 represents as a promising therapeutic strategy to mitigate CIN and improve the safety of cisplatin-based chemotherapy.

GV1001, an anticancer vaccine, exhibits diverse biological activities, including antioxidant, anti-inflammatory, anti-Alzheimer’s, and anti-atherosclerotic effects, and protects mitochondria from drug-induced injury. Cisplatin, a widely used chemotherapeutic, is effective but limited by nephrotoxicity driven by mitochondrial dysfunction in renal epithelial cells. We investigated whether GV1001 could counteract cisplatin-induced kidney injury in mice and preserve mitochondrial integrity in human renal epithelial cells. In vivo, GV1001 completely mitigated cisplatin-induced nephrotoxicity. It prevented cisplatin-induced histopathological damage, kidney injury marker expression, macrophage infiltration, endothelial-to-mesenchymal transition, inflammation, and apoptosis. In vitro, GV1001 maintained mitochondrial membrane potential, preserved ATP production, and prevented mitochondrial membrane peroxidation, possibly by binding to cardiolipin. It also reduced reactive oxygen species (ROS), cytochrome c release into the cytosol, and subsequent activation of apoptosis-related pathways elicited by cisplatin. Collectively, these findings demonstrate that GV1001 protects against cisplatin-induced nephrotoxicity (CIN) by preserving mitochondrial structure and function while suppressing downstream pathological events. By directly targeting the central mechanism of cisplatin toxicity, GV1001 emerges as a promising therapeutic strategy to mitigate CIN and improve the safety of chemotherapy.

Cluster of Differentiation 47 (CD47) functions as a key “don’t-eat-me” signal that enables cancer cells to evade macrophage-mediated immune clearance. GV1001, a 16-amino-acid peptide derived from human telomerase reverse transcriptase (hTERT), has been reported to exhibit antitumor and anti-inflammatory properties and to downregulate CD47 expression in human cells. In this study, we investigated whether GV1001 modulated CD47 expression and enhanced antitumor immunity in oral squamous cell carcinoma (OSCC). In vitro, GV1001 significantly reduced CD47 expression in both murine and human OSCC cells in dose- and time-dependent manners, resulting in a marked increase in macrophage-mediated phagocytosis. Mechanistically, GV1001 suppressed CD47 promoter activity and inhibited multiple upstream regulator expression in murine and human OSCC cell lines, while exerting minimal effects on normal human keratinocytes and fibroblasts. In vivo, GV1001 significantly inhibited tumor growth, suppressed CD47 expression, increased macrophage infiltration, and induced tumor cell necrosis and apoptosis in both murine OSCC syngeneic graft model and human OSCC xenograft model. GV1001 administered alone or in combination with cisplatin produced antitumor effects. Collectively, these findings demonstrate that GV1001 functions as a potent immunomodulatory anticancer peptide that downregulates CD47 expression and restores macrophage-mediated tumor clearance, highlighting its potential as a therapeutic strategy for OSCC.

Chemotherapy-induced mucositis (CIM) is a dose-limiting toxicity of cancer therapy that is mainly associated with mitochondrial dysfunction in epithelial cells. We investigated whether GV1001, a mitochondrial protective peptide from human telomerase reverse transcriptase (hTERT), attenuates 5-fluorouracil (5-FU)-induced mucositis in a murine model. 5-FU induced notable mortality, leukopenia, and mucositis in the gastrointestinal (GI) tract, including tongue, esophagus and small intestine. It promoted epithelial–mesenchymal transition (EMT), nuclear factor kappa-B (NF-κB) activation, systemic and mucosal inflammation, DNA damage, impaired cell proliferation, and apoptosis throughout the GI tract. GV1001 blocked 5-FU–associated mortality, significantly attenuated leukopenia, and notably prevented mucositis. GV1001 also suppressed 5-FU-induced DNA damage, EMT, loss of proliferative capacity, apoptosis, and NF-κB activation in mucosal epithelium. In normal human keratinocytes, 5-FU inhibited the cell proliferation, disrupted mitochondrial function, as evidenced by reduced mitochondrial membrane potential, increased reactive oxygen species (ROS) production, impaired electron transport chain (ETC) complex integrity, decreased ATP synthesis, and cytochrome c release into the cytosol. GV1001 markedly mitigated these 5-FU-induced mitochondrial defects. Taken together, GV1001 mitigates CIM by most likely preserving mitochondrial integrity and function, supporting its potential as a strategy to prevent cancer chemotherapy-associated mucosal injury in patients.