Therapeutic effects of tilorone on mammary carcinogenesis through downregulation of pro-inflammatory cytokines and oxidative stress

IF 3.5 4区 医学 Q2 CHEMISTRY, MEDICINAL Drug Development Research Pub Date : 2024-08-12 DOI:10.1002/ddr.22246
Abu Sufiyan Chhipa, Ayush Sharma, Srashti Verma, Snehal S. Patel
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Abstract

Tilorone dihydrochloride (tilorone) is an orally active interferon inducer with anticancer effects. The present study aimed to evaluate the anticancer effects of tilorone in breast cancer. MTT assay was done to measure the proliferation of MCF-7 and MDA-MB-231 breast cancer cells after treatment with tilorone. Mammary carcinogenesis was induced by subcutaneous injection (35 mg/kg, 0.5 mL) of dimethylbenz[a]anthracene (DMBA) in mammary pads of Sprague Dawley (SD) rats. Tumors were allowed to grow for 16 weeks till their sizes reached to 550–700 mm3, and then treated with 10 and 20 mg/kg of tilorone and standard drug doxorubicin (4 mg/kg) twice a week for 3 weeks. Normal and disease-control animals received normal saline. Tumor volumes and body weights were measured. Tumors were isolated to measure the levels of interferon-β (IFN-β), vascular endothelial growth factor-A (VEGF-A), P53 and inflammatory markers by enzyme-linked immunosorbent assay (ELISA). Serum biochemistry, lipid peroxidation (LPO) and antioxidant enzymes were measured by standard methods. Histopathology and immunohistochemistry (IHC) of P53 was done in tumor sections. Tilorone reduced the proliferation of MCF-7 and MDA-MB-231 cells with IC50 concentrations at 34.08 µM and 14.27 µM, respectively. Tilorone treatment showed reduced tumor volume, and increased survival with no significant changes in the body weights. Tilorone treatment also decreased levels of inflammatory markers and VEGF-A and increased IFN-β and P53 levels. Further, treatment with tilorone also decreased LPO and increased antioxidants levels. Histopathology of tumor sections showed normalizing morphology of treated animals. IHC of tumor sections showed increased levels of P53. In conclusion, tilorone has potential anticancer effects against breast cancer.

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替罗酮通过下调促炎细胞因子和氧化应激对乳腺癌的治疗作用。
蒂罗酮二盐酸盐(蒂罗酮)是一种具有抗癌作用的口服活性干扰素诱导剂。本研究旨在评估替罗酮对乳腺癌的抗癌作用。采用 MTT 法检测使用替罗酮治疗后 MCF-7 和 MDA-MB-231 乳腺癌细胞的增殖情况。通过皮下注射(35 毫克/千克,0.5 毫升)二甲基苯并[a]蒽(DMBA)诱导 Sprague Dawley(SD)大鼠乳垫发生乳腺癌。让肿瘤生长 16 周,直到其大小达到 550-700 立方毫米,然后用 10 和 20 毫克/千克的替罗酮和标准药物多柔比星(4 毫克/千克)治疗,每周两次,连续 3 周。正常动物和疾病对照组动物接受生理盐水治疗。测量肿瘤体积和体重。分离肿瘤,用酶联免疫吸附试验(ELISA)测定干扰素-β(IFN-β)、血管内皮生长因子-A(VEGF-A)、P53和炎症标志物的水平。血清生物化学、脂质过氧化(LPO)和抗氧化酶采用标准方法进行测定。对肿瘤切片进行组织病理学检查和 P53 免疫组织化学(IHC)检测。替罗酮可减少 MCF-7 和 MDA-MB-231 细胞的增殖,IC50 浓度分别为 34.08 µM 和 14.27 µM。替罗酮治疗可减少肿瘤体积,提高存活率,但体重无明显变化。替罗酮治疗还降低了炎症标志物和血管内皮生长因子-A的水平,提高了IFN-β和P53的水平。此外,替罗酮还能降低 LPO,提高抗氧化剂水平。肿瘤切片的组织病理学显示,治疗后的动物形态趋于正常。肿瘤切片的 IHC 显示 P53 水平升高。总之,替罗酮对乳腺癌具有潜在的抗癌作用。
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来源期刊
CiteScore
6.40
自引率
2.60%
发文量
104
审稿时长
6-12 weeks
期刊介绍: Drug Development Research focuses on research topics related to the discovery and development of new therapeutic entities. The journal publishes original research articles on medicinal chemistry, pharmacology, biotechnology and biopharmaceuticals, toxicology, and drug delivery, formulation, and pharmacokinetics. The journal welcomes manuscripts on new compounds and technologies in all areas focused on human therapeutics, as well as global management, health care policy, and regulatory issues involving the drug discovery and development process. In addition to full-length articles, Drug Development Research publishes Brief Reports on important and timely new research findings, as well as in-depth review articles. The journal also features periodic special thematic issues devoted to specific compound classes, new technologies, and broad aspects of drug discovery and development.
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