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Autophagy and head and neck cancer

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
Yunxiang Ji, Li Li, Qilei Tao, Xuyao Zhang, Jingyun Luan, Shuwei Zhao, Huanhai Liu, Dianwen Ju
Laryngeal squamous cell carcinoma (LSCC), one of the most common malignancies in the head and neck, has poor prognosis and high mortality. The need of novel and effective treatment for LSCC is urgent. Asparaginase, an enzyme-depriving asparagine, has been employed for the treatment of various cancers. In this study, we reported for the first time that asparaginase could induce remarkable cytotoxicity and caspase-dependent apoptosis in human LSCC Tu212 and Tu686 cells. Meanwhile, autophagy was triggered by asparaginase in LSCC cells, which was confirmed by accumulation of autophagosomes and the conversion of light chain 3-I (LC3-I) to LC3-II...
March 28, 2017: Applied Microbiology and Biotechnology
Domenico Mattoscio, Chiara Casadio, Claudia Miccolo, Fausto Maffini, Andrea Raimondi, Carlo Tacchetti, Tarik Gheit, Marta Tagliabue, Viviana E Galimberti, Francesca De Lorenzi, Michael Pawlita, Fausto Chiesa, Mohssen Ansarin, Massimo Tommasino, Susanna Chiocca
UBC9, the sole E2-conjugating enzyme required for SUMOylation, is a key regulator of essential cellular functions and, as such, is frequently altered in cancers. Along these lines, we recently reported that its expression gradually increases during early stages of human papillomavirus (HPV)-mediated cervical lesions transformation. However, a better understanding of how UBC9 is exploited by transforming viral oncoproteins is still needed. In the present study, we show that in human samples HPV drives UBC9 up-regulation also in very early steps of head and neck tumorigenesis, pointing to the important role for UBC9 in the HPV-mediated carcinogenic program...
March 2017: PLoS Pathogens
Namrata Adhauliya, Anupama N Kalappanavar, I M Ali, Rajeshwari G Annigeri
Autophagy is a catabolic process involving cellular recycling and is believed to play a distinct role in cell survival especially when exposed to stressors, rendering it comparable to the elixir sustaining life. It plays a significant role in various conditions like cancers, neuropathies, heart diseases, auto-immune diseases, etc. Its role in tumorigenesis and cancer therapeutics is worth exploring. Autophagy is believed to help in survival and longevity of cancer cells by buffering metabolic stress. Inhibition of autophagy in an environment of nutrient deprivation leads to cell death...
October 2016: Oral Oncology
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
Monica Benvenuto, Rosanna Mattera, Laura Masuelli, Gloria Taffera, Orlando Andracchio, Ilaria Tresoldi, Paolo Lido, Maria Gabriella Giganti, Justyna Godos, Andrea Modesti, Roberto Bei
Racemic Gossypol [(±)-GOS], composed of both (-)-GOS and (+)-GOS, is a small BH3-mimetic polyphenol derived from cotton seeds. (±)-GOS has been employed and well tolerated by cancer patients. Head and neck carcinoma (HNC) represents one of the most fatal cancers worldwide, and a significant proportion of HNC expresses high levels of antiapoptotic Bcl-2 proteins. In this study, we demonstrate that (±)-GOS inhibits cell proliferation and induces apoptosis and autophagy of human pharynx, tongue, and salivary gland cancer cell lines and of mouse salivary gland cancer cells (SALTO)...
May 2017: International Journal of Food Sciences and Nutrition
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
Tomoyuki Koguchi, Chizu Tanikawa, Jinichi Mori, Yoshiyuki Kojima, Koichi Matsuda
In response to various cellular stresses, p53 exerts its tumor suppressive effects such as apoptosis, cell cycle arrest, and senescence through the induction of its target genes. Recently, p53 was shown to control cellular homeostasis by regulating energy metabolism, glycolysis, antioxidant effect, and autophagy. However, its function in inositol synthesis was not reported. Through a microarray screening, we found that five genes related with myo-inositol metabolism were induced by p53. DNA damage enhanced intracellular myo-inositol content in HCT116 p53+/+ cells, but not in HCT116 p53-/- cells...
June 2016: International Journal of Oncology
Cheng Wang, Xi Qiang Liu, Jin Song Hou, Jian Ning Wang, Hong Zhang Huang
Oral cancer is an aggressive disease with the propensity for local recurrence and distal metastasis in the head and neck region. Currently, cisplatin-based chemotherapy or concurrent radiochemotherapy is still the first choice to treat the advanced stage cancers, in particular, the unresectable tumours. Unfortunately, innate and acquired resistance to chemotherapy agent greatly limited its effectiveness and often led to treatment failure in these patients. Hence, it is urgent to clarify the mechanisms underlying the development of chemoresistance in patients with oral cancer...
March 2016: Chinese Journal of Dental 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
Jisun Kim, Haesoon Lim, Sangwoo Kim, Hyejung Cho, Yong Kim, Xiaojie Li, Hongran Choi, Okjoon Kim
We previously reported that photodynamic therapy (PDT) induces cell death in head and neck cancer through both autophagy and apoptosis. Regulation of cell death by autophagy and apoptosis is important to enhance the effects of PDT. Autophagy maintains a balance between cell death and PDT resistance. Downregulation of heat shock protein 27 (HSP27) induces PDT resistance in head and neck cancer cells. Furthermore, HSP70 regulates apoptosis during oxidative stress. However, the role of HSPs in PDT-induced cell death through autophagy and apoptosis is unclear...
April 2016: Oncology Reports
Benjamin Cosway, Penny Lovat
Half a million new head and neck cancers are diagnosed each year worldwide. Although traditionally thought to be triggered by alcohol and smoking abuse, there is a growing subset of oropharyngeal cancers driven by the oncogenic human papilloma virus (HPV). Despite advances in both surgical and non-surgical treatment strategies, survival rates have remained relatively static emphasising the need for novel therapeutic approaches. Autophagy, the principal catabolic process for the lysosomal--mediated breakdown of cellular products is a hot topic in cancer medicine...
March 2016: Oral Oncology
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
Laura Masuelli, Fabrizio Pantanella, Giuseppe La Regina, Monica Benvenuto, Massimo Fantini, Rosanna Mattera, Enrica Di Stefano, Maurizio Mattei, Romano Silvestri, Serena Schippa, Vittorio Manzari, Andrea Modesti, Roberto Bei
Violacein (VIO; 3-[1,2-dihydro-5-(5-hydroxy-1H-indol-3-yl)-2-oxo-3H-pyrrol-3-ylidene]-1,3-dihydro-2H-indol-2-one), an indole-derived purple-colored pigment, produced by a limited number of Gram-negative bacteria species, including Chromobacterium violaceum and Janthinobacterium lividum, has been demonstrated to have anti-cancer activity, as it interferes with survival transduction signaling pathways in different cancer models. Head and neck carcinoma (HNC) represents the sixth most common and one of the most fatal cancers worldwide...
March 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Sang-Gun Ahn, Young-Hee Jin, Jung-Hoon Yoon, Soo-A Kim
Cinnamaldehyde has been shown to effectively induce apoptosis in a number of human cancer cells. In the present study, cinnamaldehyde derivative-induced apoptosis and its signaling pathways were assessed in p53-wild (SGT) and p53-mutant (YD-10B) human head and neck cancer cells. The cinnamaldehyde derivatives, 2'-hydroxycinnamaldehyde (HCA) and 2'-benzoyloxycinnamaldehyde (BCA), exhibited powerful anti-proliferative effects on SGT and YD-10B cells. The apoptotic effect induced by HCA or BCA was supported by caspase-3, -7, -9 and PARP activation, and confirmed by Annexin V-FITC/PI double staining...
November 2015: International Journal of Oncology
Hassan Chaachouay, Birgit Fehrenbacher, Mahmoud Toulany, Martin Schaller, Gabriele Multhoff, H Peter Rodemann
BACKGROUND AND PURPOSE: Blocking of the autophagy-signaling has the potential to improve cancer therapy. In the present study, the role of autophagy for radioresistance of human tumor cells was tested under clinically relevant hypoxia (1% O2). MATERIALS AND METHODS: Non-small cell lung cancer cell lines A549 and H460, head and neck squamous cell carcinoma FaDu, colon carcinoma cell line HCT116 and mouse-embryo-fibroblasts were analyzed under normoxic (21% O2) and hypoxic (0...
September 2015: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
Chandra B Lebovitz, A Gordon Robertson, Rodrigo Goya, Steven J Jones, Ryan D Morin, Marco A Marra, Sharon M Gorski
Aberrant activation or disruption of autophagy promotes tumorigenesis in various preclinical models of cancer, but whether the autophagy pathway is a target for recurrent molecular alteration in human cancer patient samples is unknown. To address this outstanding question, we surveyed 211 human autophagy-associated genes for tumor-related alterations to DNA sequence and RNA expression levels and examined their association with patient survival outcomes in multiple cancer types with sequence data from The Cancer Genome Atlas consortium...
2015: Autophagy
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
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