Affiliation:
1. Department of Medicinal Chemistry, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran
2. Department of
Breast Medicine, Cancer Hospital Chinese Academy of Medical Science, Liaoning Provincial Cancer Hospital, Shenyang, Liaoning,
110042, China
Abstract
Introduction:
Several mechanisms are known for the anticancer effects of cisplatin. However, its most wellknown
function involves binding to DNA and activating the DNA damage response.
Methods::
Despite its good effects, the treatment process often leads to chemoresistance and affects the mechanisms
that support cell survival, such as pathways that promote cell growth, apoptosis, DNA damage repair, and endocytosis.
For this reason, we investigated the effects of a new metal complex (tetradentate Schiff base zinc(II) complex) on
breast cancer cells (T-47D). We evaluated its effect on cytotoxicity, apoptosis, and drug resistance in comparison to
cisplatin.
Results:
The results of the MTT test showed that tetradentate Schiff base zinc(II) complex has good cytotoxicity compared
to cisplatin. The IC50 values for the [Zn(SB)]Cl2 complex and cisplatin after 72 h of exposure were equal to 42.1
and 276.1 μM, respectively. Real-time PCR assay confirmed that the [Zn(SB)]Cl2 complex activated the mitochondrial
pathway of apoptosis and increased the expression of Bak1 and caspase-3 genes significantly compared to cisplatin.
More importantly, the [Zn(SB)]Cl2 was able to reduce the expression of the β-catenin gene, which plays a role in drug
resistance, by 0.011 compared to the control.
Conclusion:
Therefore, we can hope for this new complex because, without the help of any β-catenin silencing agent,
it was able to inhibit the drug resistance in the T-47D cell line that overexpresses the β-catenin gene.
Publisher
Bentham Science Publishers Ltd.
Subject
Cancer Research,Pharmacology,Molecular Medicine