Ruthenium(II) complexes containing a pendant methanol amidogen induce apoptosis in SGC-7901 cells through a ROS-mediated mitochondrial dysfunction pathway
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Abstract
A phenanthrene derivative with a pendant methanol amidogen TFCPIP and its two ruthenium(II) complexes [Ru(phen)2(TFCPIP)](ClO4)2 (1) and [Ru(dmp)2(TFCPIP)](ClO4)2 (2) (phen = 1,10-phenanthroline, dmp = 2,9-dimethyl-1,10-phenanthroline, TFCPIP = 2-(2,3,5,6-tetrafluoro-4-aminoethanolphenyl)[4,5-f]-imidazo[1,10]phenanthroline) were synthesized, and the anticancer properties of the two complexes were examined. Both the complexes displayed certain anticancer activities against the selected SGC-7901, BEL-7402, HeLa, A549, MG-63, HepG2, PC-12 and SiHa cancer cells, with the highest cytotoxic activities against SGC-7901. The cell biology experiments for exploring toxicity mechanism with fluorescence imaging technique and flow cytometry demonstrated that the complexes can trigger apoptosis of SGC-7901 cells with an increase in ROS level, a decrease in mitochondrial membrane potential, and effectively inhibit cell invasion and cell growth at G2/M phase, implicating that the complexes induce cellular apoptosis through a ROS-mediated mitochondrial dysfunction pathway.
Notes
Acknowledgements
This work was supported by the Natural Science foundation of Guangdong Province (Nos2014A030307015), Special Cultivation Funds for Guangdong College Students’ Scientific and Technological Innovation, Entrepreneurship Training Project and Shaoguan university.
References
- 1.Jacques F, Isabelle S, Rajesh D, Sultan E, Colin M, Marise R, Donald MP, David F, Freddie B (2015) Int J Cancer 136:E359–E386CrossRefGoogle Scholar
- 2.Umar N, Ndumiso M, Mahmoud ES (2017) Drug Des Dev Ther 11:599–616CrossRefGoogle Scholar
- 3.Sarkar A (2018) Pharm Pat Anal 7:33–46CrossRefGoogle Scholar
- 4.Lazarević T, Rilak A, Bugarčić ŽD (2017) Eur J Med Chem 142:8–31CrossRefGoogle Scholar
- 5.Shahana D, Ganna VK (2016) Cancer Chemother Pharmacol 6:1103–1124Google Scholar
- 6.Franz H, Johannes K, Gilles G (2017) Acc Chem Res 50:2727–2736CrossRefGoogle Scholar
- 7.Bergamo A, Sava G (2007) Dalton Trans 13:1267–1272CrossRefGoogle Scholar
- 8.Anna N, Gilles G (2017) Chem Soc Rev 46:7317–7337CrossRefGoogle Scholar
- 9.Fergus EP, Sandra AB, Salvador B, Williams DC, John MK, Thorfinnur G (2017) Chem Soc Rev 46:7706–7756CrossRefGoogle Scholar
- 10.Kalaivani P, Prabhakaran R, Poornima P, Huang R, Hornebecq V, Dallemer F, Padma VV, Natarajan K (2013) RSC Adv 3:20363–20378CrossRefGoogle Scholar
- 11.Devi CS, Nagababu P, Natarajan S, Deepika N, Reddy PV, Veerababu N, Singh SS, Satyanarayana S (2014) Eur J Med Chem 72:160–169CrossRefGoogle Scholar
- 12.Zhu JW, Liu SH, Zhang GQ, Xu HH, Wang YX, Wu Y, Liu YM, Wang Y, Liang JB, Guo QF (2016) J Membr Biol 4:483–492CrossRefGoogle Scholar
- 13.Bing T, Dan W, Shang-Hai L, Hui-Hui Y, Cheng Z, Xiu-Zhen W, Chuan-Chuan Z, Yun-Jun L (2017) J Inorg Biochem 173:93–104CrossRefGoogle Scholar
- 14.Isabella R, Facchetti G, Lucchini G, Castiglioni E, Marchianò S, Ferri N (2017) Bioorgan Med Chem 25:1907–1913CrossRefGoogle Scholar
- 15.Liang ZH, Liu HY, Jiang GB, Wen JY, Liu YJ, Xiao XY (2016) Chin J Chem 34:997–1005CrossRefGoogle Scholar
- 16.Ravi KV, Kamakshi D, Praveen KY, Vinoda RM, Rajender RM, Nagamani C, Ravi C, Suman ST, Ch. Mohan R, Satyanarayana S (2018) New J Chem 42:846–859CrossRefGoogle Scholar
- 17.Nowak-Sliwinska P, Clavel CM, Pǎunescu E, Winkel MT, Griffioen AW, Dyson PJ (2015) Mol Pharm 12:3089–3096CrossRefGoogle Scholar
- 18.Sullivan BP, Salmon DJ, Meyer TJ (1978) Inorg Chem 17:3334–3341CrossRefGoogle Scholar
- 19.Collin JP, Sauvage JP (1986) Inorg Chem 25:135–141CrossRefGoogle Scholar
- 20.Mosmann T (1983) J Immunol Methods 65:55–63CrossRefGoogle Scholar
- 21.Lo KK, Lee TK, Lau JS, Poon WL, Cheng SH (2008) Inorg Chem 47:200–208CrossRefGoogle Scholar
- 22.Zhang XX, Fu ZY, Zhang ZY, Miao C, Xu PF, Wang T, Yang LY, Cheng SP (2012) Environ Sci Technol 46:11319–11326CrossRefGoogle Scholar
- 23.Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC (1985) Anal Biochem 150:76–85CrossRefGoogle Scholar
- 24.Zhang C, Lai SH, Zeng CC, Tang B, Wan D, Xing DG, Liu YJ (2016) J Biol Inorg Chem 21:1047–1060CrossRefGoogle Scholar
- 25.Zeng L, Chen Y, Liu J, Huang H, Guan R, Ji L, Chao H (2016) Sci Rep 6:19449CrossRefGoogle Scholar
- 26.Chen TF, Wong YS (2008) Cell Mol Life Sci 65:2763–2775CrossRefGoogle Scholar
- 27.Chen TF, Wong YS (2009) Int J Biochem Cell Biol 41:666–676CrossRefGoogle Scholar
- 28.Martin A, Byrne A, Burke CS, Forster RJ, Keyes TE (2014) J Am Chem Soc 136:15300–15309CrossRefGoogle Scholar
- 29.Luo Z, Yu L, Yang F, Zhao Z, Yu B, Lai H, Wong KH, Ngai SM, Zheng W, Chen T (2014) Metallomics 6:1480–1490CrossRefGoogle Scholar
- 30.Thornberry NA, Rano TA, Peterson EP, Rasper DM, Timkey T, Garcia-Calvo M, Houtzager VM, Nordstrom PA, Roy S, Vaillancourt JP, Chapman KT, Nicholson DWA (1997) J Biol Chem 272:17907–17911CrossRefGoogle Scholar
- 31.Martinou JC, Youle RJ (2011) Dev Cell 21:92–101CrossRefGoogle Scholar
- 32.Shi Y (2002) Mol Cell 9(3):459–470CrossRefGoogle Scholar
- 33.Thornberry NA, Lazebnik Y (1998) Science 281:1312–1316CrossRefGoogle Scholar
- 34.Matthew B, Luis RM, Rebeka LDG, Enrique C, Lawrence HB (2013) BMC Cell Biol 14(32):1–9Google Scholar