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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
A novel binuclear palladacycle complex inhibits melanoma growth in vitro and in vivo through apoptosis and autophagy
Biochemical Pharmacology, Volume 86, No. 12, Year 2013
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Description
Malignant melanoma is an aggressive skin cancer and it is reported to be the most treatment-resistant human cancer. Here we describe the anti-tumour activity of a novel binuclear palladacycle complex (AJ-5) in vertical growth phase (ME1402) and metastatic (WM1158) melanoma cell lines. We show that compared to normal control cell lines, AJ-5 is more effective in inhibiting the proliferation of ME1402 and WM1158 melanoma cells with IC50 values of 0.19 and 0.20 μM, respectively. Flow cytometry analyses showed that AJ-5 induced apoptosis (sub-G1 peak) which was confirmed by Annexin V-FITC/propidium iodide double-staining, nuclear fragmentation and an increase in the levels of PARP cleavage. Furthermore, AJ-5 was shown to induce both intrinsic and extrinsic apoptotic pathways as measured by PUMA, Bax and active caspases. Interestingly, AJ-5 treatment also simultaneously induced the formation of autophagosomes and led to an increase in the autophagy markers LC3II and Beclin1. Inhibition of autophagy reduced AJ-5 cytotoxicity suggesting that AJ-5 induced autophagy was a cell death and not cell survival mechanism. Moreover we show that AJ-5 induces the ATM-CHK2 DNA damage pathway and that its anti-tumour function is mediated by the p38 and ERK1/2 signalling pathways. Importantly, AJ-5 treatment efficiently reduced tumour growth in melanoma bearing mice and induced high levels of autophagy and apoptosis markers. Together these findings suggest that AJ-5 may be an effective chemotherapeutic drug in the treatment of melanoma, a highly aggressive and intractable cancer. © 2012 Elsevier B.V. All rights reserved.
Authors & Co-Authors
Aliwaini, Saeb H.
South Africa, Cape Town
Faculty of Health Sciences
Swarts, Andrew John
South Africa, Stellenbosch
Stellenbosch University
Blanckenberg, Angelique
South Africa, Stellenbosch
Stellenbosch University
Mapolie, Selwyn F.
South Africa, Stellenbosch
Stellenbosch University
Prince, Sharon
South Africa, Cape Town
Faculty of Health Sciences
Statistics
Citations: 44
Authors: 5
Affiliations: 2
Identifiers
Doi:
10.1016/j.bcp.2013.09.020
ISSN:
00062952
e-ISSN:
18732968
Research Areas
Cancer
Genetics And Genomics