Synthesis of a Novel Gold(I) Complex and Evaluation of Its Anticancer Properties in Breast Cancer Cells


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Abstract

Background:Platinum complexes are commonly used for cancer chemotherapy; however, they are not only highly-priced but also have various side effects. It is, therefore, important to design affordable anticancer drugs with minimal side effects.

Methods:We synthesized a new gold(I) complex, PF6{(BDPEA)(TPPMS) digold(I)} (abbreviated as PBTDG) and tested its cytotoxicity in MCF-7 breast cancer cells. We also evaluated the effects of PBTDG on mitochondrial membrane potential, generation of reactive oxygen species (ROS) and apoptosis in breast cancer cells.

Results:The IC50 values for PBTDG and sorafenib were found to be 1.48 µM and 4.45 µM, respectively. Exposure to PBTDG caused significant and concentration-dependent depletion of ATP and disruption of mitochondrial membrane potential. PBTDG induced 2.6, 3.6, and 5.7-fold apoptosis for 1 µM, 3 µM, and 10 µM concentrations, respectively. The induction of apoptosis by the same concentrations of sorafenib was 1.2, 1.3, and 1.6-fold, respectively. The low concentration of PBTDG (1 µM) induced the generation of ROS by 99.83%, which was significantly higher than the ROS generation caused by the same concentration of sorafenib (73.76%). The ROS induction caused by higher concentrations (5 µM) of PBTDG and sorafenib were 104.95% and 122.11%, respectively.

Conclusion:The lower concentration of PBTDG produced similar cytotoxicity and apoptotic effects that were caused by a comparatively higher concentration of known anticancer drug (sorafenib). The anticancer effects of PBTDG are attributed to its tendency to disrupt mitochondrial membrane potential, induction of apoptosis and generation of ROS. Further studies are warranted to test the anticancer effects of PBTDG in animal models of cancer.

About the authors

Haseeb Khan

Department of Biochemistry, College of Science, King Saud University

Author for correspondence.
Email: info@benthamscience.net

Anvarhusein Isab

Department of Chemistry, College of Science,, King Fahd University of Petroleum and Minerals

Email: info@benthamscience.net

Abdullah Alhomida

Department of Biochemistry, College of Science, King Saud University

Email: info@benthamscience.net

Mansour Gatasheh

Department of Biochemistry, College of Science, King Saud University

Email: info@benthamscience.net

Ali Alhoshani

Department of Pharmaceutical Chemistry, College of Pharmacy,, King Fahd University of Petroleum and Minerals

Email: info@benthamscience.net

Bashayr Aldhafeeri

Department of Pharmaceutical Chemistry, College of Pharmacy,, King Saud University

Email: info@benthamscience.net

N Prasad

Department of Biochemistry and Biotechnology, Faculty of Life Sciences, Annamalai University

Email: info@benthamscience.net

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