Journal of Clinical & Experimental Dermatology Research
Open Access
ISSN: 2155-9554
+44 1478 350008
ISSN: 2155-9554
+44 1478 350008
Saeb Aliwaini
Islamic University of Gaza, Palestine
Posters & Accepted Abstracts: J Clin Exp Dermatol Res
Recently, palladium based compounds have been investigated as potential anti-tumor agents against several cancers including melanoma. However, very little is known about their mechanism of action and whether they have any side effects in vivo is not known. This study describes the anti-tumor activity of AJ-5, a novel binuclear palladacycle complex in vertical growth phase (ME1402) and metastatic (WM1158) melanoma cell lines in vitro and in vivo. Compared to normal control cell lines, AJ-5 was shown to be more effective in inhibiting the proliferation of melanoma cells with IC50 values of less than or equal to 0.20 �?¼M. Flow cytometry analyses showed that AJ-5 induced apoptosis 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, 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-tumor function is mediated by the p38 and ERK1/2 signaling pathways. Importantly, AJ-5 treatment efficiently reduced tumor growth in melanoma bearing mice and induced high levels of autophagy and apoptosis markers.
Email: saib.iwini@gmail.com