Evaluation of naproxen and cromolyn activities against cancer cells viability, proliferation, apoptosis, p53 and gene expression of survivin and caspase-3

Abstract

We previously reported the inhibitory profiles of naproxen and cromolyn against glycogen synthase kinase-3β, which partly explain the molecular mechanisms of their anti-cancer properties. In this study, we performed a detailed biochemical evaluation of the two drugs against colorectal adenocarcinoma (Caco2), hepatocellular carcinoma (HepG2), mammary gland carcinoma (MCF7), epitheloid cervix carcinoma (Hela), lung carcinoma (A5W9) and epidermoid larynx carcinoma (Hep2) cell lines. Additionally, we performed cellular viability tests using trypan blue, proliferation MTT assay, apoptosis, p53 and real-time polymerase chain reaction for gene expression of survivin and caspase-3. Not only the two drugs were found to significantly reduce the viability of different cell lines, but they also were shown to have potent dose-dependent reduction of cellular proliferation. They exhibited cytotoxicity IC₅₀ values of 3.69 and 4.16 μM for naproxen and cromolyn, respectively. Viability and proliferation results clearly correlated with apoptosis and p53 experiments in showing that both drugs significantly raised apoptotic percentages. Furthermore, we observed a significant reduction in survivin and elevation of caspase-3 gene expression upon exposure to the two drugs. It can be concluded that both naproxen and cromolyn have significant anti-cancer properties.

• Cancer
• caspase-3
• cromolyn
• glycogen synthase kinase
• naproxen
• p53
• survivin

Acknowledgements

This study was supervised by the Faculty of Pharmacy at the Cairo University (PhD Thesis of Mohamed A. S. Al-Ghussein). The authors wish to thank the Biochemistry and Molecular Biology Unit at the Faculty of Medicine, Cairo University. The authors would like to thank also the Faculty of Pharmacy and the Drug Design unit at the University of Jordan.