Background: Malignant melanoma is aggressive skin cancer whose survival rate is extremely low. Commencing apoptosis is believed to be a significant issue in cancer treatment and targeting the apoptosis and WNT signaling pathways, which is probably a potentially successful strategy to overcome tumor plasticity in melanoma.
Method: We conducted the present in vitro study to investigate anti-proliferative and apoptotic effects of Nic-ALA, as a new compound, on A375 melanoma cell line using MTT assay and flow cytometry, respectively. The gene expression profiles of the cancer cells were obtained for Bcl-2 and Bax as the main genes of the apoptosis signaling pathway and WIF1 and beta-catenin genes from the WNT signaling pathway with qRT-PCR.
Results: Nic-ALA's cytotoxicity on A375 melanoma cell line from MTT assay was obtained with IC50 166.7, 144.2, and 146.1µM. This novel derivative induced 11.3, 46.1, and 85.7% of apoptosis in 24, 48, and 72h time points, respectively. In the treated cells, the expression of Bax, beta-catenin, and WIF1 genes increased while the expression of Bcl-2 decreased significantly at 200µM concentration and the treated times of 48 and 72h.
Conclusion: The anti-proliferation of Nic-ALA at a lower value than what we found in nicotinic acid alone represented the higher bioavailability and transport efficiency of this novel derivative through A375 melanoma cell line. Its antipoetic effects were obtained by increasing the apoptosis rate and expression of the Bax gene and reducing Bcl-2 gene expression. Up-regulation of WIF1 and beta-catenin in the WNT signaling pathway emphasized Nic-ALA's anti-cancer effect on A375 melanoma cell line.