Laboratory of Bone Tumor, The Henan Luoyang Orthopedic Hospital, Zhengzhou, Henan 450000, China.
Department of Radiology, The Henan Luoyang Orthopedic Hospital, Zhengzhou, Henan 450000, China.
Oxid Med Cell Longev. 2020 May 31;2020:7690845. doi: 10.1155/2020/7690845. eCollection 2020.
To explore fresh strategies in colorectal cancer (CRC) chemotherapy, we evaluated the capability of the ruthenium-phloretin complex in exterminating colon cancer by effectively addressing multiple apoptotic mechanisms on HT-29 cancer cells together with an animal model of colorectal cancer activated by 1,2-dimethylhydrazine and dextran sulfate sodium. Our current approach offers tangible evidence of the application of the ruthenium-phloretin complex in future chemotherapy. The complex triggers intrinsic apoptosis triggered by p53 and modulates the Akt/mTOR pathway along with other inflammatory biomarkers. The ruthenium-phloretin complex has been synthesized and successfully characterized by numerous spectroscopic methodologies accompanied by DPPH, FRAP, and ABTS assays assessing its antioxidant potential. Studies conducted in human cell lines revealed that the complex improved levels of p53 and caspase-3 while diminishing the activities of VEGF and mTOR, triggers apoptosis, and induces fragmentation of DNA in the HT-29 cells. Toxicity studies were conducted to identify the therapeutic doses of the novel complex in animal models. The outcomes of the in vivo report suggest that the complex was beneficial in repressing multiplicity of aberrant crypt foci as well as hyperplastic lesions and also promoted increased levels of CAT, SOD, and glutathione. In addition, the ruthenium-phloretin complex was able to control cell proliferation and boosted apoptotic outbursts in cancer cells associated with the increase in cellular response towards Bax while diminishing responses towards Bcl-2, NF-B, and MMP-9. Our observations from the experiments deliver testament that the ruthenium-phloretin complex has the potential to act as a promising chemotherapeutic agent in colorectal cancer because it can affect the growth of ACF and hyperplastic abrasions in the colon tissues by evoking cell death.
为了探索结直肠癌（CRC）化疗的新策略，我们评估了钌-根皮素配合物通过有效解决 HT-29 癌细胞中的多种凋亡机制以及用 1,2-二甲基肼和葡聚糖硫酸钠激活的结直肠癌细胞动物模型来杀灭结肠癌的能力。我们目前的方法为钌-根皮素配合物在未来化疗中的应用提供了切实的证据。该配合物触发 p53 引发的内在凋亡，并调节 Akt/mTOR 通路以及其他炎症生物标志物。该钌-根皮素配合物已通过多种光谱方法合成并成功表征，并通过 DPPH、FRAP 和 ABTS 测定法评估其抗氧化潜力。在人细胞系中进行的研究表明，该配合物提高了 p53 和 caspase-3 的水平，同时降低了 VEGF 和 mTOR 的活性，引发细胞凋亡，并诱导 HT-29 细胞中的 DNA 片段化。进行了毒性研究以确定新型配合物在动物模型中的治疗剂量。体内报告的结果表明，该配合物有利于抑制多发性异常隐窝病灶以及增生性病变，并促进 CAT、SOD 和谷胱甘肽水平的升高。此外，该钌-根皮素配合物能够控制细胞增殖并促进与 Bax 细胞反应增加相关的癌细胞凋亡爆发，同时降低对 Bcl-2、NF-B 和 MMP-9 的反应。我们从实验中观察到的结果证明，钌-根皮素配合物具有作为结直肠癌有前途的化疗药物的潜力，因为它可以通过引发细胞死亡来影响结直肠组织中 ACF 和增生性磨损的生长。
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