Copper complex derived from S-benzyldithiocarbazate and 3-acetylcoumarin induced apoptosis in breast cancer cell

Jhi Biau Foo, May Lee Low, Ji Hui Lim, Yan Zhi Lor, Rusyidah Zainol Abidin, Vilasini Eh Dam, Napsiah Abdul Rahman, Chaw Yee Beh, Lee Chin Chan, Chee Wun How, Yin Sim Tor, Latifah Saiful Yazan

Research output: Contribution to journalArticleResearchpeer-review

11 Citations (Scopus)

Abstract

Copper complexes have been widely studied for the anti-tumour application as cancer cells are reported to take up greater amounts of copper than normal cells. Preliminary study revealed that the newly synthesised copper complex [Cu(SBCM) 2 ] displayed marked anti-proliferative towards triple-negative MDA-MB-231 breast cancer cells. Therefore, Cu(SBCM) 2 has great potential to be developed as an agent for the management of breast cancer. The present study was carried out to investigate the mode of cell death induced by Cu(SBCM) 2 towards MDA-MB-231 breast cancer cells. The inhibitory and morphological changes of MDA-MB-231 cells treated with Cu(SBCM) 2 was determined by using MTT assay and inverted light microscope, respectively. The safety profile of Cu(SBCM) 2 was also evaluated towards human dermal fibroblast (HDF) normal cells. Confirmation of apoptosis and cell cycle arrest were determined by flow cytometry analysis. The expression of p53, Bax, Bcl-2 and MMP2 protein were detected with western blot analysis. Cu(SBCM) 2 significantly inhibited the growth of MDA-MB-231 cells in a dose-dependent manner with GI 50 18.7 ± 3.06 µM. Indeed, Cu(SBCM) 2 was less toxic towards HDF normal cells with GI 50 31.8 ± 4.0 µM. Morphological study revealed that Cu(SBCM) 2 -treated MDA-MB-231 cells experienced cellular shrinkage, membrane blebbing, chromatin condensation and formation of apoptotic bodies, suggesting that Cu(SBCM) 2 induced apoptosis in the cells, which was confirmed by Annexin-V/PI flow cytometry analysis. It was also found that Cu(SBCM) 2 induced G 2 /M phase cell cycle arrest towards MDA-MB-231 cells. The induction of apoptosis and cell cycle arrest in the present study is possibly due to the down-regulation of the mutant p53 and MMP2 protein. In conclusion, Cu(SBCM) 2 can be developed as a targeted therapy for the treatment of triple-negative breast cancer.

Original languageEnglish
Pages (from-to)505-515
Number of pages11
JournalBioMetals
Volume31
Issue number4
DOIs
Publication statusPublished - Aug 2018
Externally publishedYes

Keywords

  • Apoptosis
  • Breast cancer
  • Cell cycle arrest
  • Copper(II) Schiff-base
  • p53

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