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HNSCC and autophagy

Jinyang Cai, Ming Sun, Xin Ge, Yue Sun
Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer worldwide. The majority of HNSCCs overexpress Epidermal Growth Factor Receptor (EGFR), an essential receptor tyrosine kinase (RTK) that promotes HNSCC growth and metastasis. Therefore, EGFR has been used as an important therapeutic target to treat HNSCC. Inhibition of EGFR stimulates autophagy in cancer cells. However, the role of autophagy in EGFR inhibitor-induced cancer suppression is still in a debate. Here, we reveal that the first- and the second-generation EGFR tyrosine kinase inhibitors (TKIs) differentially affect HNSCC autophagy...
May 13, 2017: Biochemical and Biophysical Research Communications
Zhi-Jing He, Fei-Ya Zhu, Shi-Sheng Li, Liang Zhong, Hong-Yu Tan, Kai Wang
Autophagy modulation has been considered a potential therapeutic strategy for head and neck squamous cell carcinoma (HNSCC). A previous study confirmed that brazilin might possess significant anti-carcinogenic activity. However, whether brazilin induces autophagy and its roles in cell death in HNSCC are still unclear. In this study, we have shown that brazilin induced significant apoptosis in the Cal27 HNSCC cell line but not in oral keratinocyte cell line (OKC). In addition to showing apoptosis induction, we demonstrated the brazilin-induced autophagic response in the Cal27 cells, as evidenced by the formation of GFP-LC3 puncta, and also showed the upregulation of LC3-II and Beclin-1...
March 2017: Food and Chemical Toxicology
Henri Schmidt, Arutha Kulasinghe, Liz Kenny, Chamindie Punyadeera
Developing non-invasive diagnostic tools in the field of head and neck oncology has been a challenge. Analysis of circulating tumour derivatives in a patient's blood has been explored in other solid cancers. This includes analysis of circulating tumour DNA, intact circulating tumour cells (CTCs) and exosomes. These circulating tumour derivatives provide avenues of investigation which can be representative of a patient's primary tumour signature and can be assessed from a patient's blood sample. In advanced stage cancer patients, these tumour derivatives are found in higher amounts, attributed to higher cellular turnover (apoptosis, autophagy), lysed CTCs and sloughing from necrotic tumours...
October 2016: Oral Oncology
Teng-Fei Fan, Tian-Fu Wu, Lin-Lin Bu, Si-Rui Ma, Yi-Cun Li, Liang Mao, Zhi-Jun Sun, Wen-Feng Zhang
Chemotherapy is an effective weapon in the battle against cancer, but numerous cancer patients are either not sensitive to chemotherapy or develop drug resistance to current chemotherapy regimens. Therefore, an effective chemotherapy mechanism that enhances tumor sensitivity to chemotherapeutics is urgently needed. The aim of the present study was to determine the antitumor activity of dihydromyricetin (DHM) on head and neck squamous cell carcinoma (HNSCC) and its underlying mechanisms. We demonstrated that DHM can markedly induce apoptotic cell death and autophagy in HNSCC cells...
September 13, 2016: Oncotarget
Insoon Chang, Cun-Yu Wang
Chemoresistance is a major barrier to effective chemotherapy of solid tumors, including head and neck squamous cell carcinoma (HNSCC). Recently, autophagy, a highly conservative intracellular recycling system, has shown to be associated with chemoresistance in cancer cells. However, little is known about how autophagy plays a role in the development of chemoresistance in HNSCC and how autophagy is initiated when HNSCC cells undergo cytotoxic stress. Here, we report that autophagy was activated when HNSCC cells are treated with the proteasome inhibitor bortezomib, proposed as an alternative chemotherapeutic agent for both primary and cisplatin-resistant HNSCC cells...
August 26, 2016: Journal of Biological Chemistry
Yajuan Zhou, Yi Peng, Hao Tang, Xiaojun He, Zhaohua Wang, Desheng Hu, Xiaoyi Zhou
Dysregulation of mammalian target of rapamycin (mTOR) signaling contributes to head and neck squamous cell carcinoma (HNSCC) tumorigenesis and progression. In the current study, we tested the anti-HNSCC cell activity by GDC-0349, a selective ATP-competitive inhibitor of mTOR. We showed that GDC-0349 inhibited proliferation of established and primary human HNSCC cells bearing high-level of p-AKT/p-S6K. Further, it induced caspase-dependent apoptosis in the HNSCC cells. GDC-0349 blocked mTORC1 and mTORC2 activation, yet it simultaneously induced autophagy activation in HNSCC cells...
August 19, 2016: Biochemical and Biophysical Research Communications
Arya Sobhakumari, Kevin P Orcutt, Laurie Love-Homan, Christopher E Kowalski, Arlene D Parsons, C Michael Knudson, Andrean L Simons
Poor tumor response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is a significant challenge for effective treatment of head and neck squamous cell carcinoma (HNSCC). Therefore, strategies that may increase tumor response to EGFR TKIs are warranted in order to improve HNSCC patient treatment and overall survival. HNSCC tumors are highly glycolytic, and increased EGFR signaling has been found to promote glucose metabolism through various mechanisms. We have previously shown that inhibition of glycolysis with 2-deoxy-d-glucose (2DG) significantly enhanced the antitumor effects of cisplatin and radiation, which are commonly used to treat HNSCC...
2016: Oncology Research
Y Lei, B A Kansy, J Li, L Cong, Y Liu, S Trivedi, H Wen, J P-Y Ting, H Ouyang, R L Ferris
Epidermal growth factor receptor (EGFR)-targeted therapy in head and neck squamous cell carcinoma (HNSCC) patients frequently results in tumor resistance to treatment. Autophagy is an emerging underlying resistance mechanism, however, the molecular autophagy machinery in HNSCC cells and potential biomarkers of patient response to EGFR-targeted therapy remain insufficiently characterized. Here we show that the EGFR blocking with cetuximab leads to varied autophagic responses, which modulate cancer cell susceptibility to EGFR inhibition...
September 8, 2016: Oncogene
Teng-Fei Fan, Lin-Lin Bu, Wei-Ming Wang, Si-Rui Ma, Jian-Feng Liu, Wei-Wei Deng, Liang Mao, Guang-Tao Yu, Cong-Fa Huang, Bing Liu, Wen-Feng Zhang, Zhi-Jun Sun
Autophagy is considered as a double-edged sword. It can prolong the survival of cancer cells and enhance its resistance to apoptosis, and paradoxically, defective autophagy has been linked to increased tumorigenesis, but the mechanism behind this phenomenon is unclear. In this study, we demonstrated that decreased phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) was correlated with increased autophagy through the Akt/mTOR and Erk signaling pathways in human head and neck squamous cell carcinoma (HNSCC)...
December 22, 2015: Oncotarget
L Zhang, W Zhang, Y-F Wang, B Liu, W-F Zhang, Y-F Zhao, A B Kulkarni, Z-J Sun
Survivin is ubiquitously expressed in patients with head neck squamous cell carcinoma (HNSCC) and is associated with poor survival and chemotherapy resistance. Sepantronium bromide (YM155) is a selective survivin suppressant that exhibits potent antitumor activities by inducing apoptosis and autophagy in various types of cancer. However, the curative effects and underlying mechanisms of YM155 in HNSCC remain unclear. This study showed that survivin overexpression positively correlated with p-S6, p-Rb and LAMP2 but negatively correlated with the autophagic marker LC3 in human HNSCC tissues...
May 28, 2015: Cell Death & Disease
Luke Gammon, Ian C Mackenzie
Evidence from a wide range of studies indicates that hypoxia and the resulting cellular changes that are induced by HIF-1α lead to transcriptional up-regulation of a diversity of genes that play major roles in modifying the cellular behaviour of head and neck squamous cell carcinoma (HNSCC). Although the mechanisms of cell adaptation to hypoxia are still not entirely clear, many studies relate hypoxia to enhanced survival of malignant cells. Stronger staining of tissue sections for HIF-1α correlates with poor prognostic outcomes, and the hypoxic tumour microenvironment generates selective pressures that enhance the ability of cancer stem cells (CSCs) to evade therapeutically induced cell death...
February 2016: Journal of Oral Pathology & Medicine
Gunjan Guha, Wanli Lu, Shan Li, Xiaobo Liang, Molly F Kulesz-Martin, Taifo Mahmud, Arup Kumar Indra, Gitali Ganguli-Indra
Pactamycin, although putatively touted as a potent antitumor agent, has never been used as an anticancer drug due to its high cytotoxicity. In this study, we characterized the effects of two novel biosynthetically engineered analogs of pactamycin, de-6MSA-7-demethyl-7-deoxypactamycin (TM-025) and 7-demethyl-7-deoxypactamycin (TM-026), in head and neck squamous cell carcinoma (HNSCC) cell lines SCC25 and SCC104. Both TM-025 and TM-026 exert growth inhibitory effects on HNSCC cells by inhibiting cell proliferation...
2015: PloS One
Y L Xie, M Fan, R M Jiang, Z L Wang, Y Li
For decades, despite the advancement of medical science, the prognosis of head and neck squamous cell carcinoma (HNSCC), has not improved. Deltonin is one of the major active components of Dioscorea Zingiberensis Wright that has been used for anthrax, rheumatic heart disease, rheumatoid arthritis etc. By employing HNSCC FaDu cell and normal human epidermal keratinocyte, we investigate deltonin efficacy and associated mechanism in both cell culture and nude mice xenografts. Deltonin treatment selectively prevents proliferation of FaDu cells by cell-cycle arrest and induction of apoptosis, via activating checkpoint kinase Chk1and Chk2 as well as caspases 8, 9 and 3...
2015: Neoplasma
M B Berstad, L H Cheung, K Berg, Q Peng, A S V Fremstedal, S Patzke, M G Rosenblum, A Weyergang
The number of epidermal growth factor receptor (EGFR)-targeting drugs in the development for cancer treatment is continuously increasing. Currently used EGFR-targeted monoclonal antibodies and tyrosine kinase inhibitors have specific limitations related to toxicity and development of resistance, and there is a need for alternative treatment strategies to maximize the clinical potential of EGFR as a molecular target. This study describes the design and production of a novel EGFR-targeted fusion protein, rGel/EGF, composed of the recombinant plant toxin gelonin and EGF...
October 29, 2015: Oncogene
Sangeeta Shrotriya, Gagan Deep, Pamela Lopert, Manisha Patel, Rajesh Agarwal, Chapla Agarwal
Head and neck squamous cell carcinoma (HNSCC) is a major killer worldwide and innovative measures are urgently warranted to lower the morbidity and mortality caused by this malignancy. Aberrant redox and metabolic status in HNSCC cells offer a unique opportunity to specifically target cancer cells. Therefore, we investigated the efficacy of grape seed extract (GSE) to target the redox and bioenergetic alterations in HNSCC cells. GSE treatment decreased the mitochondrial electron transport chain complex III activity, increased the mitochondrial superoxide levels and depleted the levels of cellular antioxidant (glutathione), thus resulting in the loss of mitochondrial membrane potential in human HNSCC Detroit 562 and FaDu cells...
December 2015: Molecular Carcinogenesis
Haiwei Wu, Shengyun Huang, Dongsheng Zhang
Autophagy is a major intracellular pathway involving in the degradation and recycling of cytosolic material, including organelles, proteins, and ribosomes. Autophagy is commonly active in tumor cells and could be induced by stress conditions such as hypoxia, nutrient depletion and anticancer therapy. Increasing evidence supports the role of autophagy in modulating cancer behavior in head and neck squamous cell carcinoma (HNSCC). Despite recent advances in surgery combined with chemotherapy and radiotherapy, the survival rate of patients with HNSCC has not been improved substantially...
February 2015: Pathology, Research and Practice
Kai-Chun Li, Kuo-Tai Hua, Yi-Shen Lin, Chia-Yi Su, Jenq-Yuh Ko, Michael Hsiao, Min-Liang Kuo, Ching-Ting Tan
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a common cancer worldwide. Emerging evidence indicates that alteration of epigenetics might be a key event in HNSCC progression. Abnormal expression of histone methyltransferase G9a, which contributes to transcriptional repression of tumor suppressors, has been implicated in promoting cancerous malignancies. However, its role in HNSCC has not been previously characterized. In this study, we elucidate the function of G9a and its downstream mechanism in HNSCC...
July 15, 2014: Molecular Cancer
Shu-Chen Chu, Yih-Shou Hsieh, Cheng-Chia Yu, Yi-Yeh Lai, Pei-Ni Chen
BACKGROUND: Thymoquinone (TQ), an active component of Nigella sativa or black cumin, elicits cytotoxic effects on various cancer cell lines. However, the anti-cancer effects of TQ on head and neck squamous cell carcinoma (HNSCC) remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: In this study, TQ elicited a strong cytotoxic effect on SASVO3, a highly malignant HNSCC cell line. The mechanisms of this cytotoxic effect were concentration dependent. TQ also induced apoptotic cell death in SASVO3 cells as indicated by an increase in Bax expression and caspase-9 activation...
2014: PloS One
V D'Amato, R Rosa, C D'Amato, L Formisano, R Marciano, L Nappi, L Raimondo, C Di Mauro, A Servetto, C Fusciello, B M Veneziani, S De Placido, R Bianco
BACKGROUND: Cetuximab is the only targeted agent approved for the treatment of head and neck squamous cell carcinomas (HNSCC), but low response rates and disease progression are frequently reported. As the phosphoinositide 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR) pathways have an important role in the pathogenesis of HNSCC, we investigated their involvement in cetuximab resistance. METHODS: Different human squamous cancer cell lines sensitive or resistant to cetuximab were tested for the dual PI3K/mTOR inhibitor PF-05212384 (PKI-587), alone and in combination, both in vitro and in vivo...
June 10, 2014: British Journal of Cancer
M K Sannigrahi, V Singh, R Sharma, N K Panda, M Khullar
Head and neck squamous cell carcinomas (HNSCC) are one of the most common cancers worldwide, accounting for almost 50% of all malignancies in developing nations. Autophagy is a catabolic process involving turnover of long-lived proteins and organelles and is an important mechanism for cell survival under stress conditions. Autophagy has been shown to play a pivotal role in etio-pathogenesis of several cancers. Autophagy and apoptosis may be triggered by common upstream signals, and sometimes this results in combined autophagy and apoptosis, or defective apoptosis rendering immortalized epithelial cells highly tumorigenic...
April 2015: Oral Diseases
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