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Ruthenium(II) polypyridyl complexes: cellular uptake, cell image and apoptosis of HeLa cancer cells induced by double targets.
Eur J Med Chem. 2014 Jul 23; 82:82-95.EJ

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+Show Affiliations

Department of Chemistry, Jinan University, Guangzhou 510632, China.Department of Chemistry, Jinan University, Guangzhou 510632, China; Department ABCT, The Hong Kong Polytechnic University, Hong Kong.Department of Chemistry, Jinan University, Guangzhou 510632, China.Department of Chemistry, Jinan University, Guangzhou 510632, China.Department of Chemistry, Jinan University, Guangzhou 510632, China.Department of Chemistry, Jinan University, Guangzhou 510632, China.Department of Chemistry, Jinan University, Guangzhou 510632, China.Department of Chemistry, Jinan University, Guangzhou 510632, China. Electronic address: tliuliu@jnu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24878637

Citation

Yu, Qianqian, et al. "Ruthenium(II) Polypyridyl Complexes: Cellular Uptake, Cell Image and Apoptosis of HeLa Cancer Cells Induced By Double Targets." European Journal of Medicinal Chemistry, vol. 82, 2014, pp. 82-95.
Yu Q, Liu Y, Xu L, et al. Ruthenium(II) polypyridyl complexes: cellular uptake, cell image and apoptosis of HeLa cancer cells induced by double targets. Eur J Med Chem. 2014;82:82-95.
Yu, Q., Liu, Y., Xu, L., Zheng, C., Le, F., Qin, X., Liu, Y., & Liu, J. (2014). Ruthenium(II) polypyridyl complexes: cellular uptake, cell image and apoptosis of HeLa cancer cells induced by double targets. European Journal of Medicinal Chemistry, 82, 82-95. https://doi.org/10.1016/j.ejmech.2014.05.040
Yu Q, et al. Ruthenium(II) Polypyridyl Complexes: Cellular Uptake, Cell Image and Apoptosis of HeLa Cancer Cells Induced By Double Targets. Eur J Med Chem. 2014 Jul 23;82:82-95. PubMed PMID: 24878637.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ruthenium(II) polypyridyl complexes: cellular uptake, cell image and apoptosis of HeLa cancer cells induced by double targets. AU - Yu,Qianqian, AU - Liu,Yanan, AU - Xu,Lei, AU - Zheng,Chuping, AU - Le,Fangling, AU - Qin,Xiuying, AU - Liu,Yanyu, AU - Liu,Jie, Y1 - 2014/05/16/ PY - 2014/03/27/received PY - 2014/05/11/revised PY - 2014/05/12/accepted PY - 2014/6/1/entrez PY - 2014/6/1/pubmed PY - 2015/3/31/medline KW - Anticancer activity KW - Cell apoptosis KW - Cell image KW - Cellular uptake KW - Ru(II)complex KW - Telomerase SP - 82 EP - 95 JF - European journal of medicinal chemistry JO - Eur J Med Chem VL - 82 N2 - 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. SN - 1768-3254 UR - https://www.unboundmedicine.com/medline/citation/24878637/Ruthenium_II__polypyridyl_complexes:_cellular_uptake_cell_image_and_apoptosis_of_HeLa_cancer_cells_induced_by_double_targets_ L2 - https://antibodies.cancer.gov/detail/CPTC-PARP1-1 DB - PRIME DP - Unbound Medicine ER -