Hossain M Matakabbir, Soha Kazi, Rahman Arifur, Auwal Abdul, Pronoy Tasfik Ul Haque, Rashel K M, Nurujjaman M, Rahman Habibur, Roy Tapashi G, Khanam Jahan Ara, Islam Farhadul
Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi, 6205, Bangladesh.
Department of Chemistry, University of Rajshahi, Rajshahi, 6205, Bangladesh.
Discov Oncol. 2024 Dec 18;15(1):782. doi: 10.1007/s12672-024-01632-7.
Numerous chemotherapeutic agents are currently employed in cancer treatment, but many are associated with significant side effects. This study aims to identify a novel anticancer drug that minimizes or eliminates these adverse effects. The anticancer activity of the Rhodium (III) complex cis-[RhLI]I was evaluated through both in vivo and in vitro functional assays. Apoptosis in cancer cells post-treatment was assessed using microscopy and gene expression analysis. In cytotoxicity screening via the brine shrimp lethality bioassay, the compound exhibited an LC value of 25.90 µg/mL (P < 0.001). It also achieved an 88.96% inhibition of cell growth (P < 0.001), an 82.39% increase in lifespan (P < 0.001), and a significant reduction in tumor weight at a dosage of 200 µg/kg in Ehrlich ascites carcinoma (EAC)-bearing Swiss albino mice. Restoration of hematological parameters, such as RBC, WBC, and hemoglobin levels, was observed in treated tumor-bearing mice compared to untreated EAC-bearing mice. The compound inhibited the growth and proliferation of breast cancer (MCF7) cells in a dose-dependent manner, achieving a maximum inhibition of 88.9% at 200 µg/mL. Apoptotic induction in MCF7 cells occurred through the upregulation of p53, Bax, caspase-3, -8, and -9, alongside the downregulation of the anti-apoptotic protein Bcl-2. No long-term adverse effects on hematological or biochemical parameters or tissue levels were observed in the mice. Given these findings, this compound demonstrates significant cytotoxic effects and has the potential to serve as a promising chemotherapeutic agent, warranting further investigation at more advanced stages.
目前,多种化疗药物被用于癌症治疗,但许多药物都伴有明显的副作用。本研究旨在确定一种能将这些不良反应降至最低或消除的新型抗癌药物。通过体内和体外功能试验评估了铑(III)配合物顺式-[RhLI]I的抗癌活性。使用显微镜和基因表达分析评估处理后癌细胞中的凋亡情况。在通过卤虫致死生物测定法进行的细胞毒性筛选中,该化合物的LC值为25.90μg/mL(P<0.001)。在携带艾氏腹水癌(EAC)的瑞士白化小鼠中,该化合物在200μg/kg的剂量下还实现了88.96%的细胞生长抑制(P<0.001)、82.39%的寿命延长(P<0.001)以及肿瘤重量的显著降低。与未处理的携带EAC的小鼠相比,在处理后的携带肿瘤的小鼠中观察到血液学参数如红细胞、白细胞和血红蛋白水平的恢复。该化合物以剂量依赖性方式抑制乳腺癌(MCF7)细胞的生长和增殖,在200μg/mL时达到最大抑制率88.9%。MCF7细胞中的凋亡诱导是通过p53、Bax、半胱天冬酶-3、-8和-9的上调以及抗凋亡蛋白Bcl-2的下调而发生的。在小鼠中未观察到对血液学或生化参数或组织水平的长期不良影响。鉴于这些发现,该化合物显示出显著的细胞毒性作用,有潜力成为一种有前景的化疗药物,值得在更高级阶段进行进一步研究。