Ascorbic Acid Sensitizes Colorectal Carcinoma to the Cytotoxicity of Arsenic Trioxide Promoting Reactive Oxygen Species-Dependent Apoptosis and Pyroptosis

Overview

Journal Front Pharmacol

Date 2020 Mar 11

PMID 32153415

Citations 26

Authors

Wei Tian

Zhuo Wang

Nan-Nan Tang

Jia-Tong Li

Yu Liu

Wen-Feng Chu

Bao-Feng Yang

Affiliations

Soon will be listed here.

Abstract

Arsenic trioxide (ATO) is an effective therapeutic agent against acute promyelocytic leukemia (APL); however, its anti-tumor effect on solid tumors such as colorectal cancer (CRC) is still in debate. Ascorbic acid (AA) also produces a selective cytotoxic activity against tumor cells. Here, we exploit the potential benefit of ATO/AA combination in generating cytotoxicity to CRC cells, which may lay the groundwork for the potential combinational chemotherapy of CRCs. According to the results, we found that ATO and AA effectively inhibited the viability of human CRC cells in a synergistic manner. AA and ATO corporately activated caspase-3 to trigger apoptosis and upregulated the expression of caspase-1 and promoted formation of inflammasomes to induce pyroptosis. Furthermore, the stimulation of reactive oxygen species (ROS) overproduction was demonstrated as a subcellular mechanism for apoptosis and pyroptosis induced by ATO/AA combination treatment. Our findings suggest that ATO combination with a conventional dosage of AA offers an advantage for killing CRC cells. The synergistic action of ATO/AA combination might be considered a plausible strategy for the treatment of CRC and perhaps other solid tumors as well.

Citing Articles

Analysis of High-Dose Ascorbate-Induced Cytotoxicity in Human Glioblastoma Cells and the Role of Dehydroascorbic Acid and Iron.

Piotrowsky A, Burkard M, Hammerschmidt K, Ruple H, Nonnenmacher P, Schumacher M Antioxidants (Basel). 2024; 13(9).

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Research progress on the effect of pyroptosis on the occurrence, development, invasion and metastasis of colorectal cancer.

Wang X, Yin Q, Wan L, Sun R, Wang G, Gu J World J Gastrointest Oncol. 2024; 16(8):3410-3427.

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Arsenic trioxide: applications, mechanisms of action, toxicity and rescue strategies to date.

Yan M, Wang H, Wei R, Li W Arch Pharm Res. 2023; 47(3):249-271.

PMID: 38147202 DOI: 10.1007/s12272-023-01481-y.

New prospects of cancer therapy based on pyroptosis and pyroptosis inducers.

Chen Q, Sun Y, Wang S, Xu J Apoptosis. 2023; 29(1-2):66-85.

PMID: 37943371 DOI: 10.1007/s10495-023-01906-5.

Pyroptosis and inflammasomes in cancer and inflammation.

Wang J, Hua S, Bao H, Yuan J, Zhao Y, Chen S MedComm (2020). 2023; 4(5):e374.

PMID: 37752941 PMC: 10518439. DOI: 10.1002/mco2.374.

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