Hamide Malikhan - Department of Genetics, College of Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran
Elham Siasi Torbati - Department of Genetics, College of Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran
Ahmad Majd - Department of Genetics, College of Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran
Nematollah Gheibi - Cellular and Molecular Research Center, Social Determinants of Health Research Center, Research Institute for Prevention of Non-Communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran

Background: Malignant melanoma is an 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 antiproliferative and apoptotic effects of Nic-ALA, as a new compound, on A۳۷۵ melanoma cell line using MTT assay and flow cytometry, respectively. The gene expression profiles of the cancer cells were obtained for Bcl-۲ and BAX as the main genes of the apoptosis signaling pathway and WIF۱ and beta-catenin genes from the WNT signaling pathway with qRT-PCR.Results: Nic-ALA’s cytotoxicity on A۳۷۵ melanoma cell line from MTT assay was obtained with IC۵۰ ۱۶۶.۷, ۱۴۴.۲, and ۱۴۶.۱μM. This novel derivative induced ۱۱.۳, ۴۶.۱, and ۸۵.۷% of apoptosis in ۲۴, ۴۸, and ۷۲h time points, respectively. In the treated cells, the expression of BAX, beta-catenin, and WIF۱ genes increased, while the expression of Bcl-۲ decreased significantly at ۲۰۰μM concentration and the treated times of ۴۸ and ۷۲h.Conclusion: The antiproliferation 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 A۳۷۵ melanoma cell line. Its antipoetic effects were obtained by increasing the apoptosis rate and expression of the Bax gene and reducing Bcl-۲ gene expression. Upregulation of WIF۱ and beta-catenin in the WNT signaling pathway emphasized Nic-ALA’s anticancer effect on A۳۷۵ melanoma cell line.

Nicotinic acid-alpha linolenic acid, Wnt signaling pathway, WIF۱, beta-catenin, apoptosis, Melanoma