title: Ruthenium(II) polypyridyl complexes: cellular uptake, cell image and apoptosis of HeLa cancer cells induced by double targets.
abstract: Studies have shown that ruthenium complexes have relatively strong anticancer activity, cell uptake of drugs have a crucial impact on the pharmacological activity, using autofluorescence of ruthenium complexes could effectively track cancer cells and drug distribution, transport accurately in real time. In this work, we present the synthesis and detailed characterization of two novel Ru(II) complexes with hydrophobic ancillary ligands, namely [Ru(bpy)2(5-idip)](2+) (RBD) and [Ru(phen)2(5-idip)](2+) (RPD) (5-idip = 2-indole-[4,5-f][1,10]phenanthroline). We have shown that RPD can enter the HeLa cells efficiently through non-endocytotic, but energy-dependent mechanism and first accumulated in lysosomes, and then escape from the lysosomes and localize within the nuclei, efficiently lead to the inhibition of DNA transcription and translation and induced cell apoptosis. Further studies on the mechanism of apoptosis in HeLa cells demonstrate that RPD is able to induce mitochondria-mediated apoptosis in HeLa cells through activation of initiator caspase-9 and down-stream effector caspase-3 and -7 and cleavage of PARP. We have also demonstrated that RPD bind to telomeric G-quadruplex DNA effectively and selectively, together with increased p21 and p16 expression. Our findings suggest that RPD induces HeLa cell apoptosis through mitochondria-mediated pathway and inhibition of telomerase activity. RPD may be a candidate for further evaluation as a chemotherapeutic agent for human cancers.
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou 510632, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou 510632, China; Department ABCT, The Hong Kong Polytechnic University, Hong Kong.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou 510632, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou 510632, China.
authors.forename: Chuping
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou 510632, China.
authors.forename: Fangling
authors.initials: F
authors.lastname: Le
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou 510632, China.
authors.forename: Xiuying
authors.initials: X
authors.lastname: Qin
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou 510632, China.
authors.forename: Yanyu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou 510632, China. Electronic address: tliuliu@jnu.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D008968:Molecular Conformation; D041681:NIH 3T3 Cells; D011725:Pyridines / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D011725:Pyridines; D012428:Ruthenium
keywords: Anticancer activity; Cell apoptosis; Cell image; Cellular uptake; Ru(II)complex; Telomerase