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Combinatorial Low Dose Arsenic Trioxide and Cisplatin Exacerbates Autophagy via AMPK/STAT3 Signaling on Targeting Head and Neck Cancer Initiating Cells.
Front Oncol. 2020; 10:463.FO

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a highly lethal disease with high-level of epidemic both in the world and Taiwan. Previous studies support that head and neck cancer-initiating cells (HN-CICs), a subpopulation of cancer cells with enhanced stemness properties, contribute to therapy resistance and tumor recurrence. Arsenic trioxide (As2O3; ATO) has shown to be an effective anti-cancer drug targeting acute promyelocytic leukemia (APL). Combinatorial treatment with high dose of ATO and cisplatin (CDDP) exert synergistic apoptotic effects in cancer cell lines of various solid tumors, however, it may cause of significant side effect to the patients. Nevertheless, none has reported the anti-cancerous effect of ATO/CDDP targeting HN-CICs. In this study, we aim to evaluate the low dose combination of ATO with conventional chemo-drugs CDDP treatment on targeting HN-CICs. We first analyzed the inhibitory tumorigenicity of co-treatment with ATO and chemo-drugs on HN-CICs which are enriched from HNSCC cells. We observed that ATO/CDDP therapeutic regimen successfully synergized the cell death on HN-CICs with a Combination Index (CI) <1 by Chou-Talalay's analysis in vitro. Interestingly, the ATO/CDDP regimen also induced exaggerated autophagy on HN-CICs. Additionally, this drug combination strategy also empowered both preventive and therapeutic effect by in vivo xenograft assays. Finally, we provide the underlying molecular mechanisms of ATO-based therapeutic regimen on HN-CICs. Together, low dose of combinatorial ATO/CDDP regimen induced cell death as well as exacerbated autophagy via AMPK-STAT3 mediated pathway in HN-CICs.

Authors+Show Affiliations

Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan.Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan.School of Medicine, National Yang-Ming University, Taipei, Taiwan. Department of Orthopedics and Traumatology, Taipei Veterans General Hospital, Taipei, Taiwan. Department of Exercise and Health Science, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan.Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan. Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan. Cancer Progression Research Center, National Yang-Ming University, Taipei, Taiwan. Department of Dentistry, Taipei Veterans General Hospital, Taipei, Taiwan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32351887

Citation

Hu, Wei-Chun, et al. "Combinatorial Low Dose Arsenic Trioxide and Cisplatin Exacerbates Autophagy Via AMPK/STAT3 Signaling On Targeting Head and Neck Cancer Initiating Cells." Frontiers in Oncology, vol. 10, 2020, p. 463.
Hu WC, Teo WH, Huang TF, et al. Combinatorial Low Dose Arsenic Trioxide and Cisplatin Exacerbates Autophagy via AMPK/STAT3 Signaling on Targeting Head and Neck Cancer Initiating Cells. Front Oncol. 2020;10:463.
Hu, W. C., Teo, W. H., Huang, T. F., Lee, T. C., & Lo, J. F. (2020). Combinatorial Low Dose Arsenic Trioxide and Cisplatin Exacerbates Autophagy via AMPK/STAT3 Signaling on Targeting Head and Neck Cancer Initiating Cells. Frontiers in Oncology, 10, 463. https://doi.org/10.3389/fonc.2020.00463
Hu WC, et al. Combinatorial Low Dose Arsenic Trioxide and Cisplatin Exacerbates Autophagy Via AMPK/STAT3 Signaling On Targeting Head and Neck Cancer Initiating Cells. Front Oncol. 2020;10:463. PubMed PMID: 32351887.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Combinatorial Low Dose Arsenic Trioxide and Cisplatin Exacerbates Autophagy via AMPK/STAT3 Signaling on Targeting Head and Neck Cancer Initiating Cells. AU - Hu,Wei-Chun, AU - Teo,Wan-Huai, AU - Huang,Tung-Fu, AU - Lee,Te-Chang, AU - Lo,Jeng-Fan, Y1 - 2020/04/15/ PY - 2019/12/31/received PY - 2020/03/16/accepted PY - 2020/5/1/entrez PY - 2020/5/1/pubmed PY - 2020/5/1/medline KW - arsenic trioxide KW - autophagy KW - combination index KW - head and neck cancer-initiating cells KW - synergistic effects SP - 463 EP - 463 JF - Frontiers in oncology JO - Front Oncol VL - 10 N2 - Head and neck squamous cell carcinoma (HNSCC) is a highly lethal disease with high-level of epidemic both in the world and Taiwan. Previous studies support that head and neck cancer-initiating cells (HN-CICs), a subpopulation of cancer cells with enhanced stemness properties, contribute to therapy resistance and tumor recurrence. Arsenic trioxide (As2O3; ATO) has shown to be an effective anti-cancer drug targeting acute promyelocytic leukemia (APL). Combinatorial treatment with high dose of ATO and cisplatin (CDDP) exert synergistic apoptotic effects in cancer cell lines of various solid tumors, however, it may cause of significant side effect to the patients. Nevertheless, none has reported the anti-cancerous effect of ATO/CDDP targeting HN-CICs. In this study, we aim to evaluate the low dose combination of ATO with conventional chemo-drugs CDDP treatment on targeting HN-CICs. We first analyzed the inhibitory tumorigenicity of co-treatment with ATO and chemo-drugs on HN-CICs which are enriched from HNSCC cells. We observed that ATO/CDDP therapeutic regimen successfully synergized the cell death on HN-CICs with a Combination Index (CI) <1 by Chou-Talalay's analysis in vitro. Interestingly, the ATO/CDDP regimen also induced exaggerated autophagy on HN-CICs. Additionally, this drug combination strategy also empowered both preventive and therapeutic effect by in vivo xenograft assays. Finally, we provide the underlying molecular mechanisms of ATO-based therapeutic regimen on HN-CICs. Together, low dose of combinatorial ATO/CDDP regimen induced cell death as well as exacerbated autophagy via AMPK-STAT3 mediated pathway in HN-CICs. SN - 2234-943X UR - https://www.unboundmedicine.com/medline/citation/32351887/Combinatorial_Low_Dose_Arsenic_Trioxide_and_Cisplatin_Exacerbates_Autophagy_via_AMPK/STAT3_Signaling_on_Targeting_Head_and_Neck_Cancer_Initiating_Cells DB - PRIME DP - Unbound Medicine ER -
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