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Anticancer Strategy Targeting Cell Death Regulators: Switching the Mechanism of Anticancer Floxuridine-Induced Cell Death from Necrosis to Apoptosis

1
Department of Biochemistry and Molecular Biology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
2
Division of International Infectious Disease Control, Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(16), 5876; https://doi.org/10.3390/ijms21165876
Received: 11 July 2020 / Revised: 10 August 2020 / Accepted: 13 August 2020 / Published: 16 August 2020
Cell death can be broadly characterized as either necrosis or apoptosis, depending on the morphological and biochemical features of the cell itself. We have previously reported that the treatment of mouse mammary carcinoma FM3A cells with the anticancer drug floxuridine (FUdR) induces necrosis in the original clone F28-7 but apoptosis in the variant F28-7-A. We have identified regulators, including heat shock protein 90, lamin-B1, cytokeratin-19, and activating transcription factor 3, of cell death mechanisms by using comprehensive gene and protein expression analyses and a phenotype-screening approach. We also observed that the individual inhibition or knockdown of the identified regulators in F28-7 results in a shift from necrotic to apoptotic morphology. Furthermore, we investigated microRNA (miRNA, miR) expression profiles in sister cell strains F28-7 and F28-7-A using miRNA microarray analyses. We found that several unique miRNAs, miR-351-5p and miR-743a-3p, were expressed at higher levels in F28-7-A than in F28-7. Higher expression of these miRNAs in F28-7 induced by transfecting miR mimics resulted in a switch in the mode of cell death from necrosis to apoptosis. Our findings suggest that the identified cell death regulators may play key roles in the decision of cell death mechanism: necrosis or apoptosis. View Full-Text
Keywords: necrosis; apoptosis; transcriptome analysis; proteome analysis; microRNA; cell death regulator necrosis; apoptosis; transcriptome analysis; proteome analysis; microRNA; cell death regulator
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MDPI and ACS Style

Sato, A.; Hiramoto, A.; Kim, H.-S.; Wataya, Y. Anticancer Strategy Targeting Cell Death Regulators: Switching the Mechanism of Anticancer Floxuridine-Induced Cell Death from Necrosis to Apoptosis. Int. J. Mol. Sci. 2020, 21, 5876. https://doi.org/10.3390/ijms21165876

AMA Style

Sato A, Hiramoto A, Kim H-S, Wataya Y. Anticancer Strategy Targeting Cell Death Regulators: Switching the Mechanism of Anticancer Floxuridine-Induced Cell Death from Necrosis to Apoptosis. International Journal of Molecular Sciences. 2020; 21(16):5876. https://doi.org/10.3390/ijms21165876

Chicago/Turabian Style

Sato, Akira; Hiramoto, Akiko; Kim, Hye-Sook; Wataya, Yusuke. 2020. "Anticancer Strategy Targeting Cell Death Regulators: Switching the Mechanism of Anticancer Floxuridine-Induced Cell Death from Necrosis to Apoptosis" Int. J. Mol. Sci. 21, no. 16: 5876. https://doi.org/10.3390/ijms21165876

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