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Int. J. Mol. Sci. 2017, 18(3), 524; doi:10.3390/ijms18030524

Autophagy Induced by Areca Nut Extract Contributes to Decreasing Cisplatin Toxicity in Oral Squamous Cell Carcinoma Cells: Roles of Reactive Oxygen Species/AMPK Signaling

1
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan 430079, China
2
Department of Oral and Maxillofacial-Head and Neck Oncology, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079, China
3
Center of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Sanjay K. Srivastava
Received: 22 January 2017 / Revised: 14 February 2017 / Accepted: 22 February 2017 / Published: 1 March 2017
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
View Full-Text   |   Download PDF [9614 KB, uploaded 1 March 2017]   |  

Abstract

Chewing areca nut is closely associated with oral squamous cell carcinoma (OSCC). The current study aimed to investigate potential associations between areca nut extract (ANE) and cisplatin toxicity in OSCC cells. OSCC cells (Cal-27 and Scc-9) viability and apoptosis were analyzed after treatment with ANE and/or cisplatin. The expressions of proteins associated with autophagy and the AMP-activated protein kinase (AMPK) signaling network were evaluated. We revealed that advanced OSCC patients with areca nut chewing habits presented higher LC3 expression and poorer prognosis. Reactive oxygen species (ROS)-mediated autophagy was induced after pro-longed treatment of ANE (six days, 3 μg). Cisplatin toxicity (IC50, 48 h) was decreased in OSCC cells after ANE treatment (six days, 3 μg). Cisplatin toxicity could be enhanced by reversed autophagy by pretreatment of 3-methyladenine (3-MA), N-acetyl-l-cysteine (NAC), or Compound C. Cleaved-Poly-(ADP-ribose) polymerase (cl-PARP) and cleaved-caspase 3 (cl-caspase 3) were downregulated in ANE-treated OSCC cells in the presence of cisplatin, which was also reversed by NAC and Compound C. Collectively, ANE could decrease cisplatin toxicity of OSCC by inducing autophagy, which involves the ROS and AMPK/mTOR signaling pathway. View Full-Text
Keywords: areca nut extracts; reactive oxygen species; AMPK/mTOR signaling; autophagy; oral squamous cell carcinoma; cisplatin areca nut extracts; reactive oxygen species; AMPK/mTOR signaling; autophagy; oral squamous cell carcinoma; cisplatin
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Xu, Z.; Huang, C.-M.; Shao, Z.; Zhao, X.-P.; Wang, M.; Yan, T.-L.; Zhou, X.-C.; Jiang, E.-H.; Liu, K.; Shang, Z.-J. Autophagy Induced by Areca Nut Extract Contributes to Decreasing Cisplatin Toxicity in Oral Squamous Cell Carcinoma Cells: Roles of Reactive Oxygen Species/AMPK Signaling. Int. J. Mol. Sci. 2017, 18, 524.

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