Research Papers:

New perspectives of cobalt tris(bipyridine) system: anti-cancer effect and its collateral sensitivity towards multidrug-resistant (MDR) cancers

Betty Yuen Kwan Law, Yuan Qing Qu, Simon Wing Fai Mok, Hauwei Liu, Wu Zeng, Yu Han, Flora Gordillo-Martinez, Wai-Kit Chan, Keith Man-Chung Wong and Vincent Kam Wai Wong _

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Oncotarget. 2017; 8:55003-55021. https://doi.org/10.18632/oncotarget.18991

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Betty Yuen Kwan Law1,*, Yuan Qing Qu1,*, Simon Wing Fai Mok1, Hauwei Liu2, Wu Zeng1, Yu Han1, Flora Gordillo-Martinez1, Wai-Kit Chan1, Keith Man-Chung Wong2 and Vincent Kam Wai Wong1

1State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, P.R. China

2Department of Chemistry, South University of Science and Technology of China, Tangchang Boulevard, Nanshan District, Shenzhen, P.R. China

*These authors contributed equally to this work

Correspondence to:

Vincent Kam Wai Wong, email: [email protected]

Keith Man-Chung Wong, email: [email protected]

Keywords: cobalt complexes, collateral sensitivity, autophagy, anti-cancer, drug-resistant cancer

Received: January 10, 2017     Accepted: June 16, 2017     Published: July 05, 2017


Platinating compounds including cisplatin, carboplatin, and oxaliplatin are common chemotherapeutic agents, however, patients developed resistance to these clinical agents after initial therapeutic treatments. Therefore, different approaches have been applied to identify novel therapeutic agents, molecular mechanisms, and targets for overcoming drug resistance. In this study, we have identified a panel of cobalt complexes that were able to specifically induce collateral sensitivity in taxol-resistant and p53-deficient cancer cells. Consistently, our reported anti-cancer functions of cobalt complexes 1–6 towards multidrug-resistant cancers have suggested the protective and non-toxic properties of cobalt metal-ions based compounds in anti-cancer therapies. As demonstrated in xenograft mouse model, our results also confirmed the identified cobalt complex 2 was able to suppress tumor growth in vivo. The anti-cancer effect of the cobalt complex 2 was further demonstrated to be exerted via the induction of autophagy, cell cycle arrest, and inhibition of cell invasion and P-glycoprotein (P-gp) activity. These data have provided alternative metal ion compounds for targeting drug resistance cancers in chemotherapies.

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