卷 25, 编号 15 (2025)
- 年: 2025
- 文章: 6
- URL: https://kld-journal.fedlab.ru/1871-5206/issue/view/14211
Chemistry
Melittin, A Potential Game-changer in the Fight Against Breast Cancer: A Systematic Review
摘要
Introduction: Breast cancer is the most common cancer in women. Traditional treatments include endocrine therapy, chemotherapy, surgery, radiation, and immunotherapy. Recent studies suggest melittin, a component of bee venom, as a promising breast cancer treatment due to its anticancer properties: inducing cytotoxicity, apoptosis, and gene regulation.
Methods: This manuscript aims to review melittin's potential therapeutical and future implications in treating breast cancer. An extensive literature search was conducted on MEDLINE and Cochrane databases up to July 2024 using Boolean operators with a combination of keywords. After screening, data extraction, and descriptive analysis, 40 articles were retained.
Results: Experimental data and different therapeutical strategies were collected. Melittin disrupts tumor cell membranes and modulates key apoptotic pathways. Advanced delivery systems enhance their effectiveness and reduce toxicity. Combining melittin with chemotherapy shows synergistic effects, improving outcomes. Thus, melittin could be a valuable addition to breast cancer therapies.
Conclusion: Further clinical trials are essential to validate its potential and establish its role in breast cancer therapy.
1077-1084
CDH1-involved Ubiquitination of SIRT5 Promotes the Entry of Colorectal Cancer Cells into Quiescence and Enhances Cell Stemness
摘要
Background: This study explored whether the cell cycle regulator cadherin 1 (CDH1) impacts colorectal cancer cell cycle and stemness via mediating ubiquitination of sirtuin 5 (SIRT5).
Methods: We first constructed CDH1 overexpression plasmid and small interfering RNA against SIRT5 (siSIRT5) and transfected them into HCT116/HT29 cells, followed by transfection efficiency verification. The effect of CDH1 on Cyclin F/SIRT5/CDH1 protein levels in HCT116/HT29 cells was verified by Western blot. After up-regulation of CDH1, changes in SIRT5 ubiquitination (immunoprecipitation), cell cycle (cell cycle kit), proliferation (5-Bromodeoxyuridine assay), and stemness marker expressions (qRT-PCR) in HCT116/HT29 cells were detected. Rescue assays were performed to examine cell proliferation and stemness marker expressions.
Results: Overexpression of CDH1 decreased Cyclin F expression and increased SIRT5 and CDH1 expressions in HCT116/HT29 cells. Up-regulation of CDH1 suppressed SIRT5 ubiquitination, promoted G0/G1 phase blockage in HCT116/HT29 cells, boosted cell proliferation into quiescence and enhanced cell stemness. siSIRT5 counteracted the regulatory effect of CDH1 overexpression on colorectal cancer cells.
Conclusion: CDH1 promotes the entry of colorectal cancer cells into quiescence and enhances stemness by dampening SIRT5 ubiquitination.
1085-1093
HLTF Promotes the Proliferation of Osteosarcoma Cells and Cisplatin Resistance
摘要
Background: Osteosarcoma, the most common primary malignant tumor of bone tissue, is characterized by aggressive biological behavior and poor clinical outcomes. The Helicase-Like Transcription Factor (HLTF), a key regulator of DNA damage response and chromatin remodeling processes, has been increasingly recognized for its crucial role in the pathogenesis and progression of various malignancies.
Objective: This study aimed to elucidate the regulatory role of HLTF in modulating critical cellular processes, including proliferation, migration, and apoptosis in osteosarcoma cells, while concurrently investigating its potential as a molecular determinant of cisplatin chemoresistance.
Methods: The CCK-8 and colony formation assays were carried out to systematically evaluate the impact of HLTF on the proliferative capabilities of osteosarcoma cells. Additionally, the transwell and cell scratch assays were performed to determine the effect of HLTF on the migratory potential of osteosarcoma cells. Furthermore, the CCK8 assay and the subcutaneous tumorigenesis experiment were conducted in nude mice to determine the effect of HLTF on the sensitivity of osteosarcoma cells to cisplatin.
Results: Our findings revealed that silencing HLTF expression in osteosarcoma cells led to a marked suppression of both cell proliferation and invasive potential. In contrast, the overexpression of HLTF was found to augment the proliferative and migratory abilities of these cells. Remarkably, downregulating HLTF in osteosarcoma cells heightened cell sensitivity to cisplatin, which was further validated by in vivo experiments.
Conclusion: Collectively, our findings strongly indicate that HLTF acts as an oncogene, actively driving the proliferation of osteosarcoma cells and conferring resistance to cisplatin.
1094-1102
In vitro and In vivo Growth Inhibition and Apoptosis of Cancer Cells by Ethyl 4-[(4-methylbenzyl)oxy] Benzoate Complex
摘要
Background: Cancer chemotherapy is one of the best ways to treat the patients with cancer as they can remove cancer cells, which can’t be remove by radiation or surgery.
Aims:Our study is focused on identifying potent chemotherapeutic drugs with minor or no adverse side effects. Therefore, in this study, we aimed to synthesize ethyl 4-[(4-methylbenzyl)oxy] benzoate complex, a macrocyclic aromatic compound followed by testing its antineoplastic activity against Ehrlich ascites carcinoma (EAC) human breast cancer (MCF7) cells.
Methods: In vitro and in vivo assays were used for monitoring, cytotoxicity, tumor weight, survival time, tumor cell growth inhibition, and hematological parameters to investigate the anticancer effectiveness of the tested compound. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to examine the expression of growth and apoptotic related genes. Haematological and biochemical parameters were assessed to examine the host toxicity in mice.
Results: The compound exhibited notable anticancer activity against both EAC and MCF7cells. It showed 40.70 and 58.98 % cell growth inhibition at the doses of 0.5 and 1.00 mg/kg, respectively in comparison to that of control EAC-bearing mice (p <0.0001). The result is comparable with clinically used chemotherapeutic drugs cisplatin (59.2% growth inhibition at the dose of 1.0 mg/kg body weight). A four folds reduction of tumor weight (volume) of treated group at higher dose (1.0 mg/kg/day) was noted in comparison to that of untreated EAC-bearing mice. Also, the mean survival time of treated mice (1.00 mg/kg) increased by more than 83.07% when compared to that of control EAC-bearing mice (p<0.001). In addition, EAC-bearing control mice showed drastic deterioration of RBC, WBC, and % of hemoglobin, however, in the treated mice these parameters were restored towards normal levels. A dose dependent reduction of growth and proliferation of MCF7 cells was noted in compound treated cells. Most importantly, apoptosis of MCF7 was induced followed by activation of pro-apoptotic genes (p53, Bax, Parp, Caspase-3, -8, -9) and inactivation of antiapoptotic, e.g. Bcl2 gene. Toxicological studies reveal that there were changes in hematological (RBC, WBC, % of Hb) and biochemical (serum glucose, cholesterol, creatinine, SGOT, SGPT) parameters during the treatment period, however, the parameters returned towards normal levels after the treatment period, indicating no or minor toxic effect of the compound on the host.
Conclusion: The compound has promising anticancer activity with no or minimum host toxic effects. Thus, it has the potential to be formulated as an effective chemo-agent, however, further preclinical and clinical research is imperative using animal and human models.
1103-1112
Ulvan Microneedles Loaded with Photosensitizer 5-aminolevulinic Acid Inhibits Human Cervical Cancer HeLa Cells In vitro
摘要
Background: Cervical cancer encompasses highly invasive and metastatic malignant tumors with poor prognoses. Recently, microneedles have gained significant attention as a novel, non-invasive drug delivery method, offering unique advantages in tumor treatment.
Objective: This study aims to develop an ulvan-based microneedle delivery system encapsulating the photosensitizer 5-aminolevulinic acid (5-ALA-UMNs) and to investigate its inhibitory effects on the growth of human cervical cancer Hela cells.
Methods: The 5-ALA-UMNs and control microneedles (without photosensitizer) were fabricated using a twostep casting technique. The microneedles' morphology, puncture performance, and mechanical strength were assessed. Hela cells were treated in vitro with 5-ALA-UMNs, and the cellular uptake of the photosensitizer was observed using inverted fluorescence microscopy. Cell viability was determined by the CCK-8 assay to identify the optimal drug concentration. Additionally, the anti-tumor efficacy of 5-ALA-UMNs, induced via photodynamic therapy, was evaluated by Live-Dead staining and flow cytometry.
Results: The microneedles exhibited a uniform quadrangular pyramidal shape, orderly arrangement, intact needle tips, and robust mechanical strength. Inverted fluorescence microscopy confirmed the successful uptake of the photosensitizer by Hela cells, which enzymatically converted it to the fluorescent compound protoporphyrin IX. CCK-8 assays demonstrated that 5-ALA-UMNs displayed favorable cytocompatibility and safety. Live-dead staining revealed Hela cell survival rates as follows: 99.55% in the control group, 99.37% in the control microneedle group, 99.41% in the 5-ALA-UMNs group without light exposure, and 57.35% in the 5-ALA-UMNs group with light exposure (all p < 0.05). Flow cytometry results corroborated the live-dead staining findings, confirming the cytotoxic effect of 5-ALA-UMNs on tumor cells.
Conclusion: These results indicate that 5-ALA-UMNs hold promise as a tumor-targeting therapeutic.
1113-1127
The Kinesin Eg5 Inhibitor K858 Enhances Radiosensitivity in Esophageal Squamous Cell Carcinoma and Affects the Expression of Epithelial-mesenchymal Transition Related Markers: In vitro and In vivo Studies
摘要
Background: Radioresistance is the primary cause of treatment failure in esophageal squamous cell carcinoma, emphasizing the importance of identifying effective radiosensitizers.
Objectives:This study aimed to explore the effects and potential mechanisms of Eg5 inhibitor K858 on the radiosensitivity of esophageal squamous cell carcinoma TE-1 and KYSE150 cell lines, as well as xenografts (TE-1 cells).
Methods: Cellular function was assessed using CCK8, wound healing, and transwell invasion assays. Radiosensitivity parameters were derived from colony formation assays. Cell apoptosis and cell cycle were assessed using flow cytometry, whereas protein expression levels were detected using western blotting and immunohistochemistry. The xenograft model was used to observe the growth of tumors.
Results: K858 inhibited the malignant functions of TE-1 and KYSE150 cell lines. Radiosensitivity parameters were reduced after K858 treatment. The combination of K858 and irradiation markedly suppressed cell proliferation, induced apoptosis, and stimulated cell cycle arrest during the irradiation-sensitive phase. Additionally, K858, combined with irradiation, significantly increased the expression of the epithelial-mesenchymal transition marker E-cadherin and decreased the expression of N-cadherin, vimentin, MMP2, and MMP9. K858, combined with irradiation, significantly inhibited tumor growth in xenograft models.
Conclusion: K858 enhanced the radiosensitivity of esophageal squamous cell carcinoma and affected the expression of epithelial-mesenchymal transition-related markers.
1142-1159