Stabilization of Telomere DNA, and Mechanism of Apoptosis of Tumor Cells Induced by Ruthenium Complexes

doi:10.6023/A13101092

Acta Chimica Sinica ›› 2014, Vol. 72 ›› Issue (4): 473-480.DOI: 10.6023/A13101092 Previous Articles Next Articles

Article

钌配合物稳定端粒DNA的作用及其诱导细胞凋亡分子机制的研究

刘莹^a, 陈小曼^a, 张朗棋^a, 孙冬冬^a, 周艳晖^a, 陈兰美^a,b, 刘杰^a

a 暨南大学化学系广州 510632;
b 广东医学院药学院湛江 524023

投稿日期:2013-10-25 发布日期:2014-01-14
通讯作者: 刘杰 E-mail：tliuliu@jnu.edu.cn （Jie Liu）; Tel./Fax ：+86-20-8522-0223 E-mail:tliuliu@jnu.edu.cn
基金资助:
项目受国家自然科学基金（Nos.21171070，21371075）、广东省科技计划项目（No.c1211220800571）及广东省自然科学基金和中央高校基本科研业务费专项资金资助.

Stabilization of Telomere DNA, and Mechanism of Apoptosis of Tumor Cells Induced by Ruthenium Complexes

Liu Ying^a, Chen Xiaoman^a, Zhang Langqi^a, Sun Dongdong^a, Zhou Yanhui^a, Chen Lanmei^a,b, Liu Jie^a

a Department of Chemistry, Jinan University, Guangzhou 510632;
b School of Pharmacy, Guangdong Medical College, Zhanjiang 524023

Received:2013-10-25 Published:2014-01-14
Supported by:
Project supported by the National Natural Science Foundation of China (Nos. 21171070, 21371075), the Planned Item of Science and Technology of Guangdong Province (No. c1211220800571), the Natural Science Foundation of Guangdong Province and the Fundamental Research Funds for the Central Universities.

1. Stabilization of Telomere DNA, and Mechanism of Apoptosis of Tumor Cells Induced by Ruthenium Complexes.PDF(464KB)

Abstract

Telomerase is highly expressed in tumor cells, which has become an important target of anticancer drugs. Since many tumor cells were rich in G4-DNA, we investigated the capabilities of these two ruthenium complexes to stabilize G4-DNA. Two ruthenium(Ⅱ) complexes were synthesized and characterized via electrospray ionization-mass spectrometry. Since many tumor cells were rich in G4-DNA, we investigated the capabilities of these two ruthenium complexes to stabilize G4-DNA. The interactions of these compounds with G-quadruplex DNA have been studied by fluorescence spectroscopy and circular dichroism (CD) spectroscopy. The stabilization of quadruplex DNA to complex 2 was better than complex 1, and complex 2 can induce telomeric G-quadruplex to occur conformation transformation, while complex 1 cannot. The results showed that the interaction of ruthenium complexes with G-quadruplex DNA was related with the plane of ligand. A novel visual method has been developed for making a distinction between ct-DNA and HTG21 by our Ru complexes binding hemin to form the hemin-G-quadruplex DNAzyme. The results showed that in the presence of complex 1 or 2, HTG21 can fold into a G-quadruplex, but CT-DNA cannot form the G-quadruplex structure. The anticancer activities of these complexes were evaluated by using the MTT assay. Interestingly, the anti-tumor activity of complex 2 exhibited greater inhibition to HepG2 cells, suggesting the ruthenium complexes were much less toxic towards normal cells, and speculated that it targeted the telomeric G-quadruplex was play a role on anti-tumor effect. To further evaluate the characteristics of the death induced by complexes 1 and 2-treated cells staining with Hoechst is analyzed by fluorescence microscopy. These results indicated that complex 2 revealed antiproliferative activities by apoptosis. We also used PI staining and flow cytometry to assess whether the ruthenium complex 2 affected cell cycle progression in HepG2 cells. Complex 2 is a potential antitumor drugs that can induce cancer cell death by acting on cell cycle arrest in G1 phase and the formation of DNA fragments (apoptosis characteristics).

Key words: telomerase, G-quadruplex DNA, ruthenium(Ⅱ) complexes, anti-tumor activity

Cite this article

Liu Ying, Chen Xiaoman, Zhang Langqi, Sun Dongdong, Zhou Yanhui, Chen Lanmei, Liu Jie. Stabilization of Telomere DNA, and Mechanism of Apoptosis of Tumor Cells Induced by Ruthenium Complexes[J]. Acta Chimica Sinica, 2014, 72(4): 473-480.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

References

[1] McEachern, M. J.; Krauskopf, A.; Blackburn, E. H. Annu. Rev. Genet. 2000, 34, 331.

[2] Shay, J. W.; Wright, W. E. Carcinogenesis 2005, 26, 867.

[3] Shay, J. W.; Wright, W. E. Nat. Rev. Drug. Discov. 2006, 5, 577.

[4] Seenisamy, J.; Bashyam, S.; Gokhale, V.; Vankayalapati, H.; Sun, D.; Siddiqui-Jain, A.; Streiner, N.; Shin-Ya, K.; White, E.; Wilson, W. D. J. Am. Chem. Soc. 2005, 127, 2944.

[5] Yu, H.; Wang, X.; Fu, M.; Ren, J.; Qu, X. Nucleic Acids Res. 2008, 36, 5695.

[6] Zhao, C.; Geng, J.; Feng, L.; Ren, J.; Qu, X. Chem. Eur. J. 2011, 17, 8209.

[7] Rickling, S.; Ghisdavu, L.; Pierard, F.; Gerbaux, P.; Surin, M.; Murat, P.; Defrancq, E.; Moucheron, C.; Mesmaeker, K. D. Chem. Eur. J. 2010, 16, 3951.

[8] Shi, S.; Geng, X.; Zhao, J.; Yao, T.; Wang, C.; Yang, D.; Zheng, L.; Ji, L. Biochimie. 2010, 92, 370.

[9] Shi, S.; Zhao, J.; Geng, X.; Yao, T.; Huang, H.; Liu, T.; Zheng, L.; Li, Z.; Yang, D.; Ji, L. Dalton. Trans. 2010, 39, 2490.

[10] Sun, D.; Zhang, R.; Yuan, F.; Liu, D.; Zhou, Y.; Liu, J. Dalton. Trans. 2012, 41, 1734.

[11] Yu, Q.; Liu, Y.; Wang, C.; Sun, D.; Yang, X.; Liu, Y.; Liu, J. PloS one 2012, 7, e50902.

[12] Rezler, E. M.; Seenisamy, J.; Bashyam, S.; Kim, M.-Y.; White, E.; Wilson, W. D.; Hurley, L. H. J. Am. Chem. Soc. 2005, 127, 9439.

[13] Gonçalves, D. P.; Rodriguez, R.; Balasubramanian, S.; Sanders, J. K. Chem. Commun. 2006, 4685.

[14] Tan, L.; Shen, J.; Liu, J.; Zeng, L.; Jin, L.; Weng, C. Dalt Trans. 2012, 41, 4575.

[15] Xie, Y.-Y.; Huang, H.-L.; Yao, J.-H.; Lin, G.-J.; Jiang, G.-B.; Liu, Y.-J. Chem. Eur. J. 2013, 63, 603.

[16] Tan, C.; Lai, S.; Wu, S.; Hu, S.; Zhou, L.; Chen, Y.; Wang, M.; Zhu, Y.; Lian, W.; Peng, W. J. Med. Chem. 2010, 53, 7613.

[17] Sun, D.; Liu, Y.; Liu, D.; Zhang, R.; Yang, X.; Liu, J. Chem. Eur. J. 2012, 18, 4285.

[18] (a) Jiang, S.; Wang, K.; Liu, F.; Zhang, Y.; Gao, L. Acta Chim. Sinica 2005, 63, 783. (蒋尚达, 王科志, 刘芙蓉, 张永安, 高丽华, 化学学报, 2005, 63, 783); (b) Zhao, L.; Wu, B.; Gao, L.; Wang, K. Acta Chim. Sinica 2006, 64, 1402. (赵琳, 吴宝燕, 高丽华, 王科志, 化学学报, 2006, 64, 1402).

钌配合物稳定端粒DNA的作用及其诱导细胞凋亡分子机制的研究

Stabilization of Telomere DNA, and Mechanism of Apoptosis of Tumor Cells Induced by Ruthenium Complexes

PDF

Supporting Info.

Knowledge

Cited

Abstract

Cite this article

share this article

References

Related Articles 6

Recommended Articles

Metrics

Comments

[1]	Zhang Jiayu, Zhou Xiaoyu, Zhou Man, Jia Hongxia. Detection of Telomerase Activity Based on Signal Amplification of Hybridization Chain Reaction Combining with Magnetic Separation [J]. Acta Chim. Sinica, 2016, 74(6): 513-517.
[2]	Long Saran, Wan Yan, Xia Andong. Spectral Properties of Water-Soluble Conjugated Polymer PFP/DNA/Porphyrin Complex [J]. Acta Chim. Sinica, 2015, 73(7): 723-728.
[3]	Chen Couxi, Li Xueqiang, Li Tiancai, Zhou Xuezhang. Synthesis and Anti-tumor Activities of Novel 18β-Glycyrrhetinic Acid Derivatives Attaching Dithiocarbamate Units [J]. Acta Chimica Sinica, 2012, 70(07): 852-858 .
[4]	MENG Chen-Peng, WANG Shun, ZHANG Ke-Jun, JIN Hui-Le, CHEN Xi-An, HU Mao-Lin, XIONG Jing. Electrochemical Study on the Interactions between Enantiomer of 2-(5-Fluorouracil-1-acetyl)amido-1,5-dimethyl Glutarate and Double-stranded/G-quadruplex DNA [J]. Acta Chimica Sinica, 2011, 69(10): 1173-1178.
[5]	ZHOU Jiang; YUAN Gu*. Effect of pH and Cations on the Formation and Structure of Human Telomeric G-Quadruplex DNA [J]. Acta Chimica Sinica, 2007, 65(16): 1728-1732.
[6]	HUANG Yan-Ping, KONG De-Ming, ZHANG Xiao-Bin, SHEN Han-Xi, MI Huai-Feng. Real-time Quantitative Assay of Telomerase Product Using the Duplex Scorpion Primer [J]. Acta Chimica Sinica, 2004, 62(3): 274-278.