Fathy Mariam, El-Hallouty Salwa M, Mansour Ahmed S, Fahmy Mohamed, Hassan Nourhan, ElZayat Emad M
Zoology Department, Faculty of Science, Cairo University, Giza, Egypt.
Drug bioassay-cell culture laboratory, Pharmacognosy Department, Pharmaceutical and Drug Industries Division, National Research Centre, Dokki, Giza, 12622, Egypt.
Cell Biochem Biophys. 2025 Mar;83(1):865-877. doi: 10.1007/s12013-024-01519-y. Epub 2024 Oct 15.
Chemotherapy is the most common cancer treatment, and metallic anticancer compounds have generated increasing amounts of interest since the discovery of cisplatin. More recently, scientists have focused on ruthenium-based compounds as alternatives for platinum compounds, which seem like ideal therapeutic anticancer alternatives to platinum derivatives. The present study aims to assess whether one or more of three Ruthenium-based nanocomposites, namely Ru+Lysine+CTAB (RCTL), Ru+CTAB (RCT), and Ru+Lysine (RL) exhibit pronounced anti-proliferative properties against different cancer cells. Three Ruthenium nanocomposites have been synthesized by standard chemical methods and characterized by Dynamic light scattering (DLS) and Transmission electron microscopy (TEM). The cytotoxic effect of the three composites has been evaluated by MTT in-vitro assay for different human cancer cell lines, namely MCF7, HepG2, A549, and PC3 versus normal human skin cell line (BJ1). The molecular underlying mechanisms of cytotoxicity have been assessed via qRT-PCR for pro-apoptotic makers P53 and Casp-3, and anti-apoptotic marker Bcl-2 as well as flow cytometric analysis of the cell cycle. Among the 3 nanocomposites, RCTL gave the best sensitivity and cytotoxicity especially on HepG2 with IC 0.55 µg/ml but was still toxic on normal cell line with dose <12.5 µg/ml. RCTL and RCT nanocomposites have demonstrated a significant increase in the expression of P53 and Casp-3 markers versus untreated controls, but a significant reduction in the expression of Bcl-2. There was a direct correlation between the cytotoxic effect and the degree of apoptosis in the different cancer cell lines. The present study has also proved cell cycle arrest at G2-M and pre-G1 phases under the effect of IC of RCTL and RCT nanocomposites in different cancer lines with the best effect being achieved in HepG2 cells. Ruthenium nanocomposites seem to open a new avenue in cancer therapy.
化疗是最常见的癌症治疗方法，自顺铂被发现以来，金属抗癌化合物越来越受到关注。最近，科学家们将重点放在了钌基化合物上，将其作为铂化合物的替代品，它们似乎是铂衍生物理想的治疗性抗癌替代品。本研究旨在评估三种钌基纳米复合材料，即钌+赖氨酸+十六烷基三甲基溴化铵（RCTL）、钌+十六烷基三甲基溴化铵（RCT）和钌+赖氨酸（RL）中的一种或多种是否对不同癌细胞具有显著的抗增殖特性。通过标准化学方法合成了三种钌纳米复合材料，并通过动态光散射（DLS）和透射电子显微镜（TEM）进行了表征。通过MTT体外试验评估了这三种复合材料对不同人类癌细胞系，即MCF7、HepG2、A549和PC3，与正常人皮肤细胞系（BJ1）的细胞毒性作用。通过qRT-PCR检测促凋亡标志物P53和Casp-3、抗凋亡标志物Bcl-2以及细胞周期的流式细胞术分析，评估了细胞毒性的分子潜在机制。在这三种纳米复合材料中，RCTL表现出最佳的敏感性和细胞毒性，尤其是对HepG2细胞，其IC为0.55μg/ml，但在剂量<12.5μg/ml时对正常细胞系仍有毒性。与未处理的对照相比，RCTL和RCT纳米复合材料显示P53和Casp-3标志物的表达显著增加，但Bcl-2的表达显著降低。在不同癌细胞系中，细胞毒性作用与凋亡程度之间存在直接相关性。本研究还证明，在RCTL和RCT纳米复合材料的IC作用下，不同癌细胞系的细胞周期在G2-M期和G1期之前停滞，在HepG2细胞中效果最佳。钌纳米复合材料似乎为癌症治疗开辟了一条新途径。
