Arsenic trioxide-induced cytotoxicity in A549 cells: The role of
                    necroptosis

Maryam Jamil; Afshin Mohammadi-Bardbori; Omid Safa; Amin Reza Nikpoor; Azizollah Bakhtari; Mahnoosh Mokhtarinejad; Saghar Naybandi Zadeh; Amir Shadboorestan; Mahmoud Omidi

doi:10.1055/a-2076-3246

Drug Research, Table of Contents

Drug Res (Stuttg) 2023; 73(07): 417-425
DOI: 10.1055/a-2076-3246

Original Article

Arsenic trioxide-induced cytotoxicity in A549 cells: The role of necroptosis

Authors

Maryam Jamil^*

¹Department of Pharmacology & Toxicology, Faculty of Pharmacy and Pharmaceutical Sciences, Hormozgan University of Medical Sciences, Bandar Abbas, Iran

²Student research committee, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
Afshin Mohammadi-Bardbori^*

³Department of Pharmacology & Toxicology, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
Omid Safa

⁴Department of Clinical Pharmacy, School of Pharmacy and Pharmaceutical Sciences, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
Amin Reza Nikpoor

⁵Depertment of Medical Immunology, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
Azizollah Bakhtari

⁶Department of Reproductive Biology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
Mahnoosh Mokhtarinejad

¹Department of Pharmacology & Toxicology, Faculty of Pharmacy and Pharmaceutical Sciences, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
Saghar Naybandi Zadeh

⁷Department of Pharmacognosy and Pharmaceutical Biotechnology, Faculty of Pharmacy and Pharmaceutical Sciences, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
Amir Shadboorestan

⁸Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Mahmoud Omidi

¹Department of Pharmacology & Toxicology, Faculty of Pharmacy and Pharmaceutical Sciences, Hormozgan University of Medical Sciences, Bandar Abbas, Iran

Abstract

Introduction Lung cancer is one of the deadliest cancers globally. Arsenic trioxide (ATO) is still present as a highly effective drug in treating acute promyelocytic leukemia (APL). Chemotherapy resistance is one of the major problems in cancer therapy. Necroptosis, can overcomes resistance to apoptosis, and can promote cancer treatment. This study examines the necroptosis pathway in A549 cancer cells exposed to ATO.

Methods We used the MTT test to determine the ATO effects on the viability of A549 cells at three different time intervals. Also, the reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were performed in three-time intervals. The effect of ATO on apoptosis was evaluated by Annexin V / PI staining and, the RIPK1 and MLKL gene expression were measured by Real-Time PCR.

Results The ATO has dose and time-dependent cytotoxic effects, so at 24, 48, and 72 h, the IC50 doses were 33.81 ‘11.44 ‘2.535 µM respectively. A 50 μM ATO is the most appropriate to increase the MMP loss significantly at all three times. At 24 and 48 h after exposure of cells to ATO, the ROS levels increased. The RIPK1 gene expression increased significantly compared to the control group at concentrations of 50 and 100 μM; however, MLKL gene expression decreased.

Conclusions The A549 cells, after 48 h exposure to ATO at 50 and 100 μM, induces apoptosis and necroptosis. Due to the reduced expression of MLKL, it can be concluded that ATO is probably effective in the metastatic stage of cancer cells.

Key words

arsenic trioxide - apoptosis - Necroptosis - A549 cell line - MLKL - RIPK1

Full Text

References

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