Anti-tumor activity and mechanism of apoptosis of A549 induced by ruthenium complex.
Two new ruthenium (II) polypyridyl complexes [Ru(MeIm)4(pip)]2+(1) and [Ru(MeIm)4(4-npip)]2+(2) were synthesized under the guidance of computational studies (DFT). Their binding property to human telomeric G-quadruplex studied by UV-Vis absorption spectroscopy, the fluorescent resonance energy transfer (FRET) melting assay and circular dichroism (CD) spectroscopy for validating the theoretical prediction. Both of them were evaluated for their potential anti-proliferative activity against four human tumor cell lines. Complex 2 shows growth inhibition against all the cell lines tested, especially the human lung tumor cell (A549). The RTCA analysis not only validated the inhibition activity but also showed the ability of reducing A549 cells' migration. DNA-flow cytometric analysis, mitochondrial membrane potential (ΔΨm) and the scavenger measurements of reactive oxygen species (ROS) analysis carried out to investigate the mechanism of cell growth inhibition and apoptosis-inducing effect of complex 2. The results demonstrated that complex 2 induces tumor cells apoptosis by acting on both mitochondrial homeostasis destruction and death receptor signaling pathways. And those suggested that complex 2 could be a candidate for further evaluation as a chemotherapeutic agent against human tumor.
A School of life sciences, Anhui Agricultural University, Hefei, 230036, China.
Dongdong
D
Sun
A School of life sciences, Anhui Agricultural University, Hefei, 230036, China.
Zhipeng
Z
Mou
A School of life sciences, Anhui Agricultural University, Hefei, 230036, China.
Nuan
N
Li
A School of life sciences, Anhui Agricultural University, Hefei, 230036, China.
Weiwei
W
Zhang
A School of life sciences, Anhui Agricultural University, Hefei, 230036, China.
Yazhe
Y
Wang
A School of life sciences, Anhui Agricultural University, Hefei, 230036, China.
Endong
E
Yang
A School of life sciences, Anhui Agricultural University, Hefei, 230036, China. weiywswzy@163.com.
Weiyun
W
Wang
D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001667:Binding, Competitive; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002942:Circular Dichroism; D056831:Coordination Complexes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D031541:Fluorescence Resonance Energy Transfer; D054856:G-Quadruplexes; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D015394:Molecular Structure; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012428:Ruthenium / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013053:Spectrophotometry; D013997:Time Factors
D000970:Antineoplastic Agents; D056831:Coordination Complexes; D017382:Reactive Oxygen Species; D012428:Ruthenium; D004247:DNA
Anti-tumor activity; Apoptosis; G-quadruplex; Mitochondrial pathway; Ruthenium complex