Sharon Prince
University of Cape Town, South Africa
Title: The binuclear palladacycle, AJ-5, is a promising chemotherapeutic agent in a subset of breast cancers, advanced melanomas and sarcomas
Biography
Biography: Sharon Prince
Abstract
Cancer continues to represent one of the most serious health problems worldwide and there is an urgent need to develop improved anti-tumour therapies. Compared to organic chemotherapeutic molecules, metal complexes offer a much more diverse chemistry and have been shown to have important chemotherapeutic applications. This study describes the anti-tumour activity of a novel binuclear palladacycle complex (AJ-5) in several types of cancers. Compared to normal control cells, AJ-5 is more cytotoxic in a subset of advanced melanoma cells, metastatic breast cancer cells and sarcomas, with IC50 values of less than or equal to 0.20 μM. AJ-5 was found to induce apoptosis by flow cytometry (sub G-1 peak), 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, cytochrome c release 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, it was shown that AJ-5 induces the ATM-CHK2 DNA damage pathway and that its anti-tumour function is mediated by MAPK 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 several cancers.