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Effects of an aryl hydrazone derivative of naproxen on HepG2 liver cancer and HGF gingival fibroblasts cell lines

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Abstract

Nonsteroidal anti-inflammatory drugs are suggested to have anti-cancer effects in many studies, but elucidation of mode of action remains a challenging task. The present study was aimed to evaluate the effect of an Aryl hydrazone derivative of Naproxen (AHD) on HepG2 liver cancer cells and HGF gingival fibroblasts. The mentioned cell lines were randomly divided into control groups and test groups exposed to 1, 10, 20, 50, and 100 μg/mL of Naproxen and (AHD). The cytotoxic effects of the compounds were measured using the MTT assay. The rate of apoptosis and cell cycle were also evaluated using flow cytometry at 24 and 48 h. The data were compared between groups using one-way analysis of variance. The results showed a significantly reduced viability of liver cancer cells by 20, 50, and 100 μg/mL  of Naproxen, and AHD after 24 h (IC50 = 51.35 μg/ mL and IC50 = 87.05 μg/ mL) and 48 h (IC50 = 24.92  μg/ mL and IC50 = 20.82 μg/ mL) (p < 0.0001). Exposure to Naproxen and AHD increased the late apoptosis rate 9.10 and 6.42 times respectively in HepG2 cancer cells compared to the control group at 48 h. (**** p < 0.0001). In the group treated with AHD, a significant decrease in G1 and a significant increase in S and G2 phases occurred in the percentage of arrested cells in HepG2 cancer at 24 h (****p < 0.0001). A significant decrease in G1 and a significant increase in S phases of Naproxen and AHD occurred in the percentage of arrested cells on HepG2 cancer at 48 h (***p < 0.001, **p < 0.01, ****p < 0.0001 ***p < 0.001 respectively). The results of this study demonstrate that Naproxen and the evaluated AHD induce cytotoxic effects in the HepG2 cancer cell line through the apoptosis pathway by cell arrest in the G2/M phase. The less cytotoxicity was observed in gingival fibroblasts than in cancer cells.

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Acknowledgements

Authors are grateful to the Toxicogenomics Laboratory, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, and all the people who helped to conduct the present research. There is no funding.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Faculty of Pharmacy and Pharmaceutical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

    Raziyeh Sadat Miri Lavasani, Sanaz Pashapour & Zahra Mousavi

  2. Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

    Ali Almasirad

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  1. Raziyeh Sadat Miri Lavasani
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  2. Sanaz Pashapour
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  3. Ali Almasirad
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  4. Zahra Mousavi
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Contributions

ZM and AA conceived the idea of research, ZM supervised all anti-cancer evaluations, AA carried out the design and supervision of the synthesis of AHD. RSML performed MTT assay, Flow cytometry and statistical analysis. ZM and SP wrote/revised the manuscript. The results of this study are based on the Pharm. D. thesis of (RSML) presented by the Toxicogenomics Laboratory of Islamic Azad University of Medical Sciences.

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Correspondence to Zahra Mousavi.

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The Study protocol was approved by the ethics committee of the Pharmaceutical Sciences Branch of the Islamic Azad University, Tehran.

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Lavasani, R.S.M., Pashapour, S., Almasirad, A. et al. Effects of an aryl hydrazone derivative of naproxen on HepG2 liver cancer and HGF gingival fibroblasts cell lines. Nucleus 66, 183–193 (2023). https://doi.org/10.1007/s13237-023-00428-4

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