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

Xu, Zhi; Huang, Chun‐Ming; Shao, Zhang; Zhao, Xiaoping; Wang, Meng; Yan, Tinglin; Zhou, Xiaocheng; Jiang, Erhui; Liu, Ke; Shang, Zhengjun

doi:10.3390/ijms18030524

Cited by 21 publications

(16 citation statements)

References 39 publications

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“…This speculation is further verified in our recent studies that long‐term treatment of malignant cells with non‐cytotoxic concentrations of ANE or ANE 30‐100K (both ≤1.25 μg/mL) result in increased resistance against stressed conditions such as cisplatin and serum deprivation through elevated autophagic activities . Similar increased cisplatin resistance was also observed in oral carcinoma cell lines after 6‐day ANE (3 μg/mL) treatment …”

Section: Introductionsupporting

confidence: 73%

Clathrin‐mediated endocytosis is required for ANE 30‐100K‐induced autophagy

Liu

et al. 2017

J Oral Pathology Medicine

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Section: Introductionsupporting

confidence: 73%

Clathrin‐mediated endocytosis is required for ANE 30‐100K‐induced autophagy

Liu

et al. 2017

J Oral Pathology Medicine

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“…The three cell lines were treated with 100 nM rapamycin for 24 h. When 3-MA (2 mM) ( 27 ) or chloroquine phosphate (10 µM) ( 28 ) were used in combination with rapamycin, the rate of cell migration was significantly reduced. As displayed in Fig.…”

Section: Resultsmentioning

confidence: 99%

Knockdown of KPNA2 inhibits autophagy in oral squamous cell carcinoma cell lines by blocking p53 nuclear translocation

Lin

Gao

et al. 2018

Oncol Rep

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Oral squamous cell carcinoma (OSCC), one of the 10 most common types of neoplasms in the US, constitutes ~90% of all cases of oral malignancies. Chemoresistance and metastasis are difficult to avoid during the course of treatment, leading to a poor prognosis and a high mortality rate for patients with OSCC. Autophagy, a critical conserved cellular process, has been reported to be highly associated with the regulation of chemoresistance and metastasis of cancer cells. The present study investigated the role of karyopherin α2 (KPNA2), a member of the importin α family, which may serve an important role in p53 nucleocytoplasmic transport in the process of OSCC autophagy. In the CAL-27, SCC-15 and Tca8113 OSCC cell lines, we observed that the downregulation of KPNA2 suppressed cell migration and cisplatin resistance, using wound-healing, Transwell and CCK-8 assays. Additionally, the results of western blot analysis and transmission electron microscopy (TEM) analysis indicated that the knockdown of KPNA2 inhibited autophagy. We confirmed that the inhibition of autophagy with anti-autophagy agents decreased the migration and cisplatin resistance of OSCC cells. We hypothesized that the suppression of cell migration and cisplatin resistance induced by KPNA2 knockdown may be associated with the inhibition of autophagy. To identify the underlying mechanism, further experiments determined that KPNA2 affects the level of autophagy via regulating the p53 nuclear import. Thus, the present study demonstrated that the function of KPNA2 in the process of autophagy may be p53-dependent, and by regulating the translocation of p53, KPNA2 can support autophagy to promote the chemoresistance and metastasis of OSCC cells.

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“…Recent reports related autophagy to clinical cancer therapy failure, including chemotherapy and radiotherapy . For example, the extract of areca nut decreased cisplatin sensitivity in OSCC patients through the activation of autophagy . Similarly, it has been reported that autophagy protected ovarian cancer cells against metformin‐induced apoptosis.…”

Section: Discussionmentioning

confidence: 99%

A 5′ AMP‐Activated Protein Kinase Enzyme Activator, Compound 59, Induces Autophagy and Apoptosis in Human Oral Squamous Cell Carcinoma

Weng

Dokla

et al. 2018

Basic Clin Pharma Tox

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5' AMP-activated protein kinase enzyme (AMPK), a master regulator of cellular metabolism, is recognized for its association with various metabolic diseases, inflammation and cancer. In this study, we aimed to investigate the role of compound 59, an AMPK activator, in a panel of oral squamous cell carcinoma (OSCC) cell lines. The antiproliferative effects of compound 59 were assessed by MTT assays, flow cytometry, Western blotting, confocal microscopy and transmission electron microscopy. Relative to OSCC cells, normal human oral keratinocytes were almost insensitive to compound 59 treatment. Compound 59 induced apoptosis as indicated by caspase activation and PARP cleavage. In addition, it inhibited JAK/STAT3 signalling, arrested cells in the G1 phase, increased reactive oxygen species (ROS) generation and promoted autophagy. Interestingly, pre-treatment with a protein tyrosine phosphatase (PP2A) inhibitor, cantharidin, partially reversed compound 59-induced down-regulation of p-JAK2 and p-STAT3, thereby suggesting the involvement of a protein tyrosine phosphatase. Together, these findings substantiate the potential of compound 59 for the treatment of OSCC patients.

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

Cited by 21 publications

References 39 publications

Clathrin‐mediated endocytosis is required for ANE 30‐100K‐induced autophagy

Clathrin‐mediated endocytosis is required for ANE 30‐100K‐induced autophagy

Knockdown of KPNA2 inhibits autophagy in oral squamous cell carcinoma cell lines by blocking p53 nuclear translocation

A 5′ AMP‐Activated Protein Kinase Enzyme Activator, Compound 59, Induces Autophagy and Apoptosis in Human Oral Squamous Cell Carcinoma

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