Clotrimazole decreases human breast cancer cells viability through alterations in cytoskeleton-associated glycolytic enzymes

Meira, Débora Dummer; Marinho-Carvalho, Monica M.; Teixeira, Cesar Augusto Antunes; Veiga, Venício Féo da; Poian, Andrea T. Da; Holandino, Carla; Freitas, Marta Sampaio de; Sola‐Penna, Mauro

doi:10.1016/j.ymgme.2004.11.012

Cited by 73 publications

(75 citation statements)

References 32 publications

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“…The association of glycolytic enzymes to these intracellular ultrastructures is an important mechanism of regulation of glucose consumption, determining if it will be completely oxidized, fermented, or used as carbon source for biosynthesis (17,19,20,22,36,(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53). The more associated the enzymes are, the less oxidized glucose is, being preferentially fermented and used to biosynthesis.…”

Section: Discussionmentioning

confidence: 99%

“…It has been stated that in conditions that glycolysis occurs at elevated rates, such as cancer, the particulate fraction of glycolytic enzyme, that is the fractions of these enzymes that are associated to intracellular ultrastructures, increases (17,41). Additionally, the detachment of these enzymes from intracellular ultrastructures has been proved to the lethal to tumor cells and is proposed as a target for anticancer drugs development (41,50,51,(54)(55)(56)(57). Similarly, promoting the association of glycolytic enzymes, these intracellular ultrastructures might be a possible mechanism for the prevention of complications associated to DM owing to the diminished glucose metabolism.…”

Section: Discussionmentioning

confidence: 99%

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Metformin reverses hexokinase and phosphofructokinase downregulation and intracellular distribution in the heart of diabetic mice

Silva¹,

Ausina²,

Alencar³

et al. 2012

IUBMB Life

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SummaryDiabetes mellitus is characterized by hyperglycemia and its associated complications, including cardiomyopathy. Metformin, in addition to lowering blood glucose levels, provides cardioprotection for diabetic subjects. Glycolysis is essential to cardiac metabolism and its reduction may contribute to diabetic cardiomyopathy. Hexokinase (HK) and phosphofructokinase (PFK), rate-limiting enzymes of glycolysis, are downregulated in cardiac muscle from diabetic subjects, playing a central role on the decreased glucose utilization in the heart of diabetic subjects. Thus, the aim of this study was to determine whether metformin modulates heart HK and PFK from diabetic mice. Diabetes was induced by streptozotocin injection on male Swiss mice, which were treated for three consecutive days with 250 mg/kg metformin before evaluating HK and PFK activity, expression, and intracellular distribution on the heart of these subjects. We show that metformin abrogates the downregulation of HK and PFK in the heart of streptozotocin-induced diabetic mice. This effect is not correlated to alteration on the enzymes' transcription and expression. However, the intracellular distribution of both enzymes is altered in diabetic hearts that show increased activity of the soluble fraction when compared to the particulate fraction. Moreover, this pattern is reversed upon the treatment with metformin, which is correlated with the effects of the drug on the enzymes activity. Altogether, our results support evidences that metformin alter the intracellular localization of HK and PFK augmenting glucose utilization by diabetic hearts and, thus, conferring cardiac protection to diabetic subjects.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Metformin reverses hexokinase and phosphofructokinase downregulation and intracellular distribution in the heart of diabetic mice

Silva¹,

Ausina²,

Alencar³

et al. 2012

IUBMB Life

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“…It was found to inhibit the formation of protrusions and to suppress cancer invasion and metastasis, indicating that cytoplasmic protrusions are an important tool for cancer cell invasion (Yamada et al, 2009). Using clotrimazole (an anti-fungal azole derivative) to induce membrane protrusion dysfunction, Meira et al observed the absence of membrane alterations to adjacent cells, thus inactivating the invasion process (Meira et al, 2004). Studying the role of cellular protrusions using reconstituted matrices, Kramer et al found that tumour cell invasion begins with the formation of unique projections that are thought to maximise the cell membrane surface area (Kramer et al, 1986).…”

Section: 1305 Sem Features Of Advancing Breast Cancer Cells and Intementioning

confidence: 99%

Distinctive Features of Advancing Breast Cancer Cells and Interactions with Surrounding Stroma Observed Under the Scanning Electron Microscope

Jaafar¹,

Sharif²,

Murtey³

2012

Asian Pacific Journal of Cancer Prevention

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“…After 72 h, cells were incubated with MTT reagent (Sigma, St Louis, MO, USA) and processed as previously described (Meira et al, 2005). Concentrations resulting in cell growth inhibition of 30 (IC 30 ), 50 (IC 50 ) and 80% (IC 80 ) were calculated for cisplatin.…”

Section: Mtt and Clonogenic Assaysmentioning

confidence: 99%

Combination of cetuximab with chemoradiation, trastuzumab or MAPK inhibitors: mechanisms of sensitisation of cervical cancer cells

et al. 2009

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BACKGROUND: Cervical cancer (CC) annually kills 288 000 women worldwide. Unfortunately, responses to chemoradiation are partial and are of short duration. As anti-EGFR monoclonal antibodies sensitise tumours, we investigated cetuximab's toxicity plus chemoradiation on CC cells, which express different EGFR levels. METHODS: EGFR, HER2, AKT and MAPK expression and phosphorylation status were determined by western blotting. Cytotoxicity was assessed by MTT or clonogenic assays (CA) in cell lines treated with cetuximab alone or in combinations. RESULTS: Cetuximab with cisplatin and radiation achieved maximum cytotoxic effects for A431, Caski and C33A cells (high, intermediate and low EGFR expression, respectively) in CA. Cetuximab efficiently decreased MAPK and AKT phosphorylation in A431 cells but slightly less in Caski and C33A cells. To check whether further EGFR, HER2 or MAPK inhibition would improve cetuximab's cytotoxicity, we combined it with an EGFR tyrosine kinase inhibitor (TKI), trastuzumab or a MEK1/2 inhibitor (PD98059). In Caski, but not in C33A cells, cetuximab cooperated with the TKI, reducing cell survival and AKT and MAPK phosphorylation. However, cetuximab with trastuzumab or PD98059 reduced survival and MAPK phosphorylation of both cell lines. CONCLUSION: Our data suggest that cetuximab combined with chemoradiation, trastuzumab or MAPK inhibitors has useful applications for CC treatment, independently of EGFR expression. Cervical cancer (CC) is a common malignancy which kills 288 000 women annually. Radical hysterectomy and radiation therapy are standard treatments for early-stage invasive CC, whereas pelvic radiation has been used for locally advanced cancers. Recently, an improved survival of patients with locally advanced CC was reported when platinum-based chemotherapy was combined with radiation treatment (Ota et al, 2007). However, despite technological advances, up to 35% of all CC patients will develop persistent/ recurrent/metastatic disease (Bellone et al, 2007).Infection of human keratinocytes by oncogenic HPV subtypes is critical for cervical carcinogenesis, however, it is not sufficient for cancer development. Among other molecular cofactors investigated, epidermal growth factor (EGF) receptor (EGFR) overexpression is frequent in CC and is an independent predictor of poor prognosis in advanced stage tumours (Kersemaekers et al, 1999). Epidermal growth factor receptor, a 170-kDa transmembrane glycoprotein, belongs to the ErbB/HER family of receptors, which include HER2 (ErbB2), HER3 (ErbB3) and HER4 (ErbB4). Ligand binding leads to the formation of homo-or heterodimers with other members of the family, receptor autophosphorylation and activation of signalling pathways, which regulate cell proliferation, survival and transformation (Citri and Yarden, 2006). A major EGFR signalling route, the mitogen-activated protein kinases (MAPK) pathway is often deregulated in cancer cells. The activation of this pathway, comprised by Ras, Raf, MEK1/2 and extracellular signal-regulated kinase (ERK)1...

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Clotrimazole decreases human breast cancer cells viability through alterations in cytoskeleton-associated glycolytic enzymes

Cited by 73 publications

References 32 publications

Metformin reverses hexokinase and phosphofructokinase downregulation and intracellular distribution in the heart of diabetic mice

Metformin reverses hexokinase and phosphofructokinase downregulation and intracellular distribution in the heart of diabetic mice

Distinctive Features of Advancing Breast Cancer Cells and Interactions with Surrounding Stroma Observed Under the Scanning Electron Microscope

Combination of cetuximab with chemoradiation, trastuzumab or MAPK inhibitors: mechanisms of sensitisation of cervical cancer cells

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