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2017 ; 8
(33
): 55003-55021
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New perspectives of cobalt tris(bipyridine) system: anti-cancer effect and its
collateral sensitivity towards multidrug-resistant (MDR) cancers
#MMPMID28903398
Law BYK
; Qu YQ
; Mok SWF
; Liu H
; Zeng W
; Han Y
; Gordillo-Martinez F
; Chan WK
; Wong KM
; Wong VKW
Oncotarget
2017[Aug]; 8
(33
): 55003-55021
PMID28903398
show ga
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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