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Triclosan induces apoptosis in Burkitt lymphoma-derived BJAB cells through caspase and JNK/MAPK pathways

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Abstract

Burkitt's lymphoma (BL) is the fastest growing human tumor. Current treatment consists of a multiagent regimen of cytotoxic drugs with serious side effjects including tumor lysis, cardiotoxicity, hepatic impairment, neuropathy, myelosuppression, increased susceptibility to malignancy, and death. Furthermore, therapeutic interventions in areas of BL prevalence are not as feasible as in high-income countries. Therefore, there exists an urgent need to identify new therapies with a safer profile and improved accessibility. Triclosan (TCS), an antimicrobial used in personal care products and surgical scrubs, has gained considerable interest as an antitumor agent due to its interference with fatty acid synthesis. Here, we investigate the antitumor properties and associated molecular mechanisms of TCS in BL-derived BJAB cells. Dose-dependent cell death was observed following treatment with 10–100 µM TCS for 24 h, which was associated with membrane phospholipid scrambling, compromised permeability, and cell shrinkage. TCS-induced cell death was accompanied by elevated intracellular calcium, perturbed redox balance, chromatin condensation, and DNA fragmentation. TCS upregulated Bad expression and downregulated that of Bcl2. Moreover, caspase and JNK MAPK signaling were required for the full apoptotic activity of TCS. In conclusion, this report identifies TCS as an antitumor agent and provides new insights into the molecular mechanisms governing TCS-induced apoptosis in BL cells.

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Acknowledgement

The authors are grateful to the Deanship of Scientific Research, King Saud University for funding this research project through Vice Deanship of Scientific Research Chairs (DSRVCH).

Funding

This work was funded by the Deanship of Scientific Research, King Saud University, Vice Deanship of Scientific Research Chairs (DSRVCH).

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  1. Mohammad A. Alfhili and Hosni A. M. Hussein contributed equally to this work and share first authorship

Authors and Affiliations

  1. Chair of Medical and Molecular Genetics Research, Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, 11433, Saudi Arabia

    Mohammad A. Alfhili

  2. Division of Hematology/Oncology, Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC, 27834, USA

    Mohammad A. Alfhili, Youngyong Park & Myon Hee Lee

  3. Department of Microbiology & Immunology, Brody School of Medicine, East Carolina University, Greenville, NC. 27834, USA

    Hosni A. M. Hussein & Shaw M. Akula

  4. Faculty of Science, Assiut Branch, Al Azhar University, Assiut, 71524, Egypt

    Hosni A. M. Hussein

  5. Lineberger Comprehensive Cancer Center, University of North Carolina-Chapel Hill, Chapel Hill, NC, 27599, USA

    Myon Hee Lee

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Contributions

MAA, HAMH, MHL, and SMA conceived and designed research. MAA, HAMH, and YP performed experiments. MAA, YP, MHL, and SMA analyzed data, prepared figures, and wrote manuscript. MAA, HAMH, MHL, and SMA critically reviewed the final draft and approved the initial submission.

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Correspondence to Myon Hee Lee or Shaw M. Akula.

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Alfhili, M.A., Hussein, H.A.M., Park, Y. et al. Triclosan induces apoptosis in Burkitt lymphoma-derived BJAB cells through caspase and JNK/MAPK pathways. Apoptosis 26, 96–110 (2021). https://doi.org/10.1007/s10495-020-01650-0

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