Multidrug resistance in oral squamous cell carcinoma: The role of vacuolar ATPases

Pérez‐Sayáns, Mario; Martín, Juan Enrique Pérez; Barros, Francisco; Díz, Pilar; Rey, José Manuel Gándara; García‐García, Abel

doi:10.1016/j.canlet.2010.03.019

Cited by 72 publications

(47 citation statements)

References 83 publications

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“…Very little information is known about the importance of MDR and Pgp expression in HNSCC. Although Pgp levels and mRNA have been noted in recurrent oral SCC and in oral mucosa with increasing severity of dysplasia, insignificant Pgp levels have been found in oral SCC cell lines (Pérez-Sayáns et al, 2010). Treatment of different cell lines with vincristine shows that Pgp can be induced by genetic induction of the MDR1 gene.…”

Section: Pharmacogenomicsmentioning

confidence: 98%

“…Recent evidence suggests that V-ATPases may play a role in acidification of the tumor microenvironment by secreting protons through the plasma membrane. Pretreatment with proton pump inhibitors has been found to sensitize tumor cell lines to the effects of different chemotherapy drugs (Pérez-Sayáns et al, 2010). Although it has been shown that pH regulation in oral SCC lines is mediated by vacuolar proton-pump ATPases, and that this pH regulation is involved in cell transformation, none of these inhibitors were proven to be useful in Oral Squamous cell carcinomas (OSCC).…”

Section: Pharmacogenomicsmentioning

confidence: 99%

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Head and Neck Cancer

Thomas¹,

Jefferson²

2013

Genomic and Personalized Medicine

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PredispositionThe predominant environmental risk factors for developing head and neck squamous cell carcinoma (HNSCC) identified to date are the use of alcohol and tobacco, immunosuppression, and exposure to high-risk human papilloma virus (HPV). However, not all smokers and drinkers develop cancers. In fact, only 10-15% of smokers develop lung cancer, and an even a smaller proportion is diagnosed with HNSCC (Ho et al., 2007). Therefore, genetic predisposition and other host factors may play an equally important role in tumorigenesis.Processed tobacco contains at least 30 known carcinogens, and cigarette smoke contains approximately 50 known carcinogens and procarcinogens. Nearly all carcinogens and procarcinogens require activation via metabolizing enzymes. Likewise, detoxifying enzymes act to deactivate carcinogens and their intermediate byproducts. The collective metabolizing enzymes and detoxifying enzymes are known as xenobiotic-metabolizing enzymes, and are found in the liver and upper aerodigestive tract (UADT) mucosa. Genetic polymorphisms of these enzymes modify an individual's response to carcinogen exposure, and consequently the potential of the exposure to incite the development of HNSCC (Ho et al., 2007).The most significant of the procarcinogens contained in cigarette smoke are the aromatic hydrocarbons such as benzo(a)pyrene, tobacco-specific nitrosamines, and aromatic amines. Benzo(a)pyrenediol epoxide (BPDE) is a toxic metabolite of benzo(a)pyrene that exerts its mutagenic effect mostly by irreversibly binding to DNA, forming BPDE-DNA adducts, or by DNA oxidation. Nitrosamines produce free radical compounds known to cause DNA fragmentation. The individual capacity for nucleotide excision and repair of normal DNA after BPDE-induced damage was shown to correlate with HNSCC development independent of age, sex, ethnicity, smoking status, or alcohol use in a case-control study (Cheng et al., 1998).The genetic determination of DNA repair capacity is also associated with an individual's susceptibility to the development of HNSCC. DNA repair capacity for removing BPDEinduced DNA adducts is considered an independent biomarker for the risk of developing smoking-related HNSCC (Wang et al., 2010). Mutagen hypersensitivity or an individual's capacity for DNA repair against free radical damage and its relevance to the development of HNSCC was examined by Schantz and coworkers (1997). The relationship between the risk of HNSCC, nutrition, and mutagen hypersensitivity was studied in HNSCC patients and controls. Dietary intake of various antioxidants such as vitamins C and E and carotenoids, cigarette smoking, alcohol use, and body mass index (BMI) were also examined. The study found that mutagen hypersensitivity was strongly associated with increased risk of HNSCC. Also, high intakes of vitamins C and E and some carotenoids were independently related to a decreased risk of HNSCC.The role of genomic instability in the development of HNSCC was further elucidated in a study of patients with Fanconi anemia, a rare a...

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Section: Pharmacogenomicsmentioning

confidence: 98%

Section: Pharmacogenomicsmentioning

confidence: 99%

Head and Neck Cancer

Thomas¹,

Jefferson²

2013

Genomic and Personalized Medicine

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“…[8][9][10] Since OSCC has a relatively high rate of occult metastases, 11) to the majority of patients with advanced cancer, chemotherapy is an indispensable therapy. However, the resistant to chemotherapy agent was reported to be the most critical problem, [12][13][14][15][16] thus a wide array of structurally diverse drugs with explicit mechanism are badly needed. Furthermore OSCC is a highly complex multifactorial process involving numerous and multi-step genetic events, personalized therapy became a focus of attention.…”

mentioning

confidence: 99%

Apoptotic Effects of Diosgeninlactoside on Oral Squamous Carcinoma Cells <i>in Vitro</i> and <i>in Vivo</i>

Wang

Sun

et al. 2014

Biological & Pharmaceutical Bulletin

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Diosgenyl saponins possess a variety of biological functions. Herein, we demonstrate a new type of diosgenyl saponin derivatives that inhibit cellular proliferation of oral squamous cell carcinoma (OSCC) cell lines. Thereafter, we analyzed these cells' expression of apoptosis-related proteins. Crucial proteins that participate in apoptosis regulation including caspases 8, 9, and 3, and cleaved Bid were activated and upregulated accompanied by increased concentrations of diosgenyl saponins. Meanwhile, Bcl-2 was downregulated and mitochondrial membrane potential decreased. In our mice model of OSCC, compound 1 showed potent inhibition of solid tumor growth and salient antitumor activity. Diosgenyl β-D-galactopyranosyl-(1→4)-β-Dglucopyranoside might induce OSCC cell line apoptosis through extrinsic and intrinsic pathways, and might provide a mechanistic background for the development of this new type of diosgenylsaponin derivatives into anti-oral cancer agents against OSCC.Key words diosgenyl saponin; oral squamous cell carcinoma (OSCC); apoptosis Oral cancer is one kind of the head and neck tumors, and is the eighth most common occurring cancers in the whole world.1) The factors related to this disease are reported to be tobacco usage, betel quid chewing, excessive alcohol drinking, dietary micronutrient deficiency, and human papilloma virus infection, etc. Its high incidence can be found worldwidely, including nearly all the continents, and caused serious public health threats.2,3) More than 90% of all oral cancers are attributed to oral squamous cell carcinoma (OSCC). OSCC most commonly appears in tongue and the floor of the mouth, whereas it less frequently occurs in other locations such as lip, buccal mucosa, retromolar area, gingiva, soft palate and the back of the tongue and hard palate.4) It is generally accepted that OSCC is caused by mutations of oral keratinocyte: DNA mutations increase hyperplasia of keratinocyte and become pre-malignant or potentially malignant disorders (which are commonly manifested as Leukoplakia or Erythroplakia clinically). Next, they will deteriorate further into the stage of solid cancer or even penetrate across the epithelial basement membrane, and finally metastasize to lymph nodes, bone, brain, liver and other sites.5,6) So it will cause severe threat to the individual life. Also the tendency of its incidence is increasing continuously, around 480000 newly diagnosed cancers per year was reported globally.7) Therefore efficient treatment of OSCC is in urgent demand and is expected to play a key role in combating the overall oral cancers. Current treatment of OSCC has primarily relied on surgery, radiation, and chemotherapy or a combination of these methods. Unfortunately, the symptomatic tend to be diagnosed at an advanced stage, and the 5-year survival rates are still as low as 50% for the past decades. [8][9][10] Since OSCC has a relatively high rate of occult metastases, 11) to the majority of patients with advanced cancer, chemotherapy is an indispensable therapy. However,...

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Section: Introductionmentioning

confidence: 99%

“…It relies on the energy transfer protons generated by the hydrolysis of ATP to produce the electrochemical gradient of the transmembrane and to regulate the transmembrane pH gradient (18). V-ATPase has been considered to be one of the important targets for overcoming an acidic tumor microenvironment (5,18). In addition, several studies have demonstrated that PPIs, which directly inhibit V-ATPase at the cellular level, reverted chemoresistance in drug-resistant tumors and directly induced tumor cell death, indicating that targeting V-ATPase may be an option for reversing multidrug resistance (17).…”

Section: Introductionmentioning

confidence: 99%

Cluster of differentiation 147 mediates chemoresistance in breast cancer by affecting vacuolar H+-ATPase expression and activity

et al. 2018

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Abstract. Vacuolar H + -ATPase (V-ATPase) serves a key role in adjusting and maintaining the intracellular pH, as well as in regulating the drug resistance of tumor cells. In recent years, the expression level of V-ATPase has been considered to be able to predict the sensitivity of breast cancer cells to chemotherapy drugs. Cluster of differentiation 147 (CD147) is known to serve a key role in the development and progression of breast cancer. The present study aimed to identify the role CD147 and V-ATPase in chemoresistance in breast cancer, and to characterize the regulation of CD147 on V-ATPase. Firstly, the expression levels of CD147 and V-ATPase were detected in chemotherapy-resistance breast cancer samples. It was demonstrated that V-ATPase was highly expressed in chemotherapy-resistance breast cancer samples, and that its expression was correlated with CD147 expression. Subsequently, MCF-7 and MDA-MB-231 cells were used to study the regulatory effect of CD147 on the expression and function of V-ATPase. Gene transfection or small interfering RNA transfection were used to control the expression of CD147 in the two cell lines. The results revealed that the overexpression of CD147 increased the expression of V-ATPase in MCF-7 cells, whereas CD147 knockdown decreased V-ATPase expression in MDA-MB-231 cells. It was also observed that CD147 affected the V-ATPase activity, regulating the transmembrane pH gradient of cancer cells. These results demonstrated that CD147 was associated with the sensitivity of chemotherapeutic drugs of epirubicin and docetaxel, while pantoprazole was able to partially reverse the CD147-mediated chemoresistance in breast cancer. Therefore, the current study provided a possible mechanism for further examination of drug resistance in breast cancer.

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Multidrug resistance in oral squamous cell carcinoma: The role of vacuolar ATPases

Cited by 72 publications

References 83 publications

Head and Neck Cancer

Head and Neck Cancer

Apoptotic Effects of Diosgeninlactoside on Oral Squamous Carcinoma Cells <i>in Vitro</i> and <i>in Vivo</i>

Cluster of differentiation 147 mediates chemoresistance in breast cancer by affecting vacuolar H+-ATPase expression and activity

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