Research Article |
Corresponding author: Mohamed Saadh ( mjsaadh@yahoo.com ) Academic editor: Plamen Peikov
© 2023 Mohamed Saadh.
This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Citation:
Saadh M (2023) Antiproliferative activity of ruthenium complex II against human cancer cell in vitro. Pharmacia 70(3): 797-801. https://doi.org/10.3897/pharmacia.70.e111410
|
Despite significant advancements in cancer treatment, there is a constant need for new and effective therapeutic options. One such potential weapon in the fight against cancer is ruthenium complex II. In this article, we synthesized, characterized, and studied the activity of dithiocyanato-N-bis[8-(diphenylphosphino)quinoline]ruthenium (II) [Ru(N-P)2(NCS)2] against MCF-7 human adenocarcinoma cells and the MRC-5 cell lines from fetal lung fibroblast-like cells as normal cells, as well as the mechanisms of action and selectivity. This study demonstrated that [Ru(N-P)2(NCS)2] has cytotoxic activity against MCF-7 with IC50 values of 7.56 µg/ml and cytotoxic activity against MRC-5 cell lines with IC50 values of 576.6 µg/ml. [Ru(N-P)2(NCS)2] showed more selective cytotoxic activity against MCF-7 cancer cell lines than MRC-5 normal cell lines. . This study demonstrated the potent apoptotic activity of ruthenium complex II by determining the activation of caspase-3, highlighting its potential as a therapeutic agent in cancer treatment. The [Ru(N-P)2(NCS)2] is considered promising for researchers investigating putative biological activities, particularly antitumor and immune-related activity.
Anticancer agents, coordination complexes, cytotoxic activity, ruthenium complex, tumor cell lines
Cancer, a devastating disease that affects millions of lives worldwide, requires innovative and effective treatment options (
The Ruthenium Complex, comprising of a ruthenium atom bonded to organic ligands, possesses exceptional properties that make it an attractive choice for cancer treatment. The use of the Ruthenium Complex in cancer treatment offers several advantages over traditional therapies. Firstly, its selective targeting of cancer cells ensures that healthy cells are spared from unnecessary damage. This targeted approach not only reduces the risk of side effects but also improves the overall quality of life for patients undergoing treatment (
In this study, the dithiocyanato-N-bis[8(diphenylphosphino)quinoline]ruthenium (II), [Ru(N-P)2(NCS)2], was synthesized, characterized using FT-IR and X-ray crystallography, and its putative cytotoxicity against MCF-7 human brest cancer cell lines and MRC-5 normal cell lines was determined to assess the selectivity of the ruthenium complex for cancer cells. The cytotoxic mechanism of [Ru(N-P)2(NCS)2] was determined by measuring the apoptosis executor caspase3 activity.
Silver nitrate, dichloromethane, acetone, potassium thiocyanate, heat-inactivated fetal bovine serum, L-Glutamine trypan blue dye, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) were obtained from Sigma-Aldrich (St. Louis, MO, USA). MCF-7 and MRC-5 cell lines were obtained from the ECACC (Salisbury, UK). The caspase-3 colorimetric assay kit was obtained from (KeyGen Biotech, Nanjing, China).
[Ru(N-P)2Cl2] was synthesized using published procedures (
MCF-7 and MRC-5 cells were grown in DMEM with 10% heat-inactivated fetal bovine serum, L-glutamine (2 mM), and penicillin/streptomycin (100 U/ml, 100 µg/ml) at 37 °C in humidified air with 5% CO2 (
After 12 h of attachment, 2.0 ml of fresh medium containing [Ru(N-P)2(NCS)2] (2, 5, 10, 20, 50, 100 µg/ml) was added to six-well plates containing 4 × 104 cells/ml. Cell biochemistry was assessed 24 hours post-treatment.
Final concentrations of 2, 5, 10, 20, 50, and 100 µg/ml of [Ru(N-P)2(NCS)2] were added to approximately 1 × 104 MCF-7 cells and incubated for 72 hours. After exposure, wells were incubated for four hours with 3-(4,5-dimethylthiazol-2w-yl)-2,5-diphenyl tetrazolium bromide (MTT). After dissolving the MTT crystals in 100 µl of DMSO solution, a multi-well plate reader (Bio-Tek Instrument, USA) measured the optical density (OD) at 570 nm with a reference wavelength of 630 nm (
MCF-7 cells were treated for 48 hours with [Ru(N-P)2(NCS)2] (25, 50, and 100 µg/mL) before total protein extraction with RIPA reagent. At 405 nm, caspase-3 activity was measured using a commercial kit (KeyGen Biotechnology, Nanjing, China) and an ELISA reader (ELX800, Promega, US).
Data analysis was performed using the SPSS software. Diferences among the studied groups were determined based on one-way analysis of variance (ANOVA) followed by Tukey’s multiple comparisons as post-hoc tests. All of the values are the mean ± SD and are representative of the results of three independent experiments.
Under nitrogen gas, [Ru(N-P)2(NCS)2] was prepared in dry dioxane. Characterization of [Ru(N-P)(NCS)2] was completed via single crystal X-ray. Fig.
The infrared spectrum of [Ru(N-P)2(NCS)2] (Fig.
The MTT assay measured doxorubicin’s cytotoxicity. As a positive control, doxorubicin had IC50 values of 4.36 and 6.3 μg/ml against MCF-7 and MRC5. [Ru(N-P)2(NCS)2] showed high cytotoxic and antiproliferative activity against MCF-7 cell lines (IC50 = 7.56 µg/ml), but low cytotoxic and antiproliferative activity against normal MRC-5 cell lines (IC50 = 576.6 µg/ml) (Table
Caspase3 activity, the executor of apoptosis, was measured to determine the cytotoxic mechanism of [Ru(N-P)2(NCS)2]. Caspase 3 is activated by [Ru(N-P)2(NCS)2] (P < 0.05), and [Ru(N-P)2(NCS)2] dose-dependently induced caspase-3 (Fig.
Ruthenium complexes offer several advantages over platinum-based drugs. Firstly, ruthenium complexes can exhibit a broader range of coordination geometries, allowing for a more precise and tailored design of drug molecules (
Targeted cancer therapy focuses on specific molecular targets in cancer cells, thus minimizing damage to normal cells and increasing treatment effectiveness (
[Ru(N-P)2(NCS)2] represents a promising solution for combating MCF-7 human breast cancer cell lines. [Ru(N-P)2(NCS)2] has ability to selectively target cancer cells, induce apoptosis, and overcome drug resistance makes it a valuable addition to the field of cancer therapy. Therefore, [Ru(N-P)2(NCS)2] is a promising chemotherapeutic agent for the prevention and treatment of human breast cancer. However, further research is needed to fully understand its mechanism of action, optimize its delivery, and ensure its long-term safety.