Rottlerin and Cancer: Novel Evidence and Mechanisms

Maioli, Emanuela; Torricelli, Claudia; Valacchi, Giuseppe

doi:10.1100/2012/350826

Cited by 67 publications

(67 citation statements)

References 91 publications

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“…The level of TG2 is associated with the expression of Bcl-2 (16): Silencing TGM2 downregulates the level of Bcl-2 (17). The compound rotterlin regulates downstream proteins, including Bcl-2 and nuclear factor-κB, through the TG2/protein kinase C δ axis (18). Thus, silencing TGM2 may promote apoptosis and increase the chemosensitivity of MDA-MB-231 cells to TXT by downregulating Bcl-2.…”

Section: Discussionmentioning

confidence: 99%

Silencing of TGM2 reverses epithelial to mesenchymal transition and modulates the chemosensitivity of breast cancer to docetaxel

Sun

Liu

2015

Experimental and Therapeutic Medicine

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Abstract. Epithelial to mesenchymal transition (EMT) plays a critical role in drug resistance. The aim of the present study was to further elucidate its role by examining the effect of tissue transglutaminase (TG2) on EMT and drug resistance in breast cancer. An antisense lentiviral (LV) short hairpin (sh)RNA construct specific to the TG2 gene (TGM2) was designed, synthesized and stably transfected into MDA-MB-231 cells to silence TGM2 by RNA interference (RNAi). The transfected cells expressed low levels of TG2 and constituted the RNAi (TGM2-shRNA) group. A control (NC) group was also established by transfecting MDA-MB-231 cells with scrambled shRNA. The expression levels of TG2, E-cadherin, vimentin and B-cell lymphoma (Bcl)-2 in the cells were examined via western blotting. The transfected MDA-MB-231 cells were divided into four groups, two of which were treated with doxetaxel (TXT): NC, RNAi, TXT and RNAi + TXT groups,. Cell proliferation was analyzed by MTT assay and cell apoptosis was detected by flow cytometry. An in vivo assay was also conducted, in which MDA-MB-231 cells transfected with scrambled shRNA or TGM2-shRNA were subcutaneously implanted into nude mice. After 2 weeks, TXT or vehicle was intraperitoneally administered at a dose of 10 mg/kg on day 1 of every week and tumor growth was monitored. Following the silencing of TGM2 in the MDA-MB-231 cells, the cells showed changes in morphology, indicating that an increased expression of TG2 was associated with a mesenchymal morphology. Transfection of the cells with TGM2-shRNA affected the expression of TG2, E-cadherin, vimentin and Bcl-2. In the MTT assay, the proliferation of MDA-MB-231 cells was significantly inhibited in the RNAi group compared with the control group (P<0.05), and the inhibitory effect increased in a time-dependent manner. Following treatment with TXT for 48 h, apoptosis was significantly promoted in the RNAi + TXT group compared with that in the other groups (P<0.05). Measurement of the tumors in the nude mice indicated that the combination of RNAi and TXT brought about a stronger antitumor effect than either treatment alone. These results suggest that the downregulation of TG2 reversed EMT and modulated the chemosensitivity of breast cancer to TXT. TG2 may be an important predictive and prognostic factor for the treatment efficacy of chemotherapy in patients with breast cancer.

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Section: Discussionmentioning

confidence: 99%

Silencing of TGM2 reverses epithelial to mesenchymal transition and modulates the chemosensitivity of breast cancer to docetaxel

Sun

Liu

2015

Experimental and Therapeutic Medicine

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“…Other studies imply a protein kinase C (PKC)-d/transglutaminase 2 (TG2)-dependent mechanism [185]. Early autophagy induction and late apoptosis caused by rottlerin, thus, are due to multiple cellular effects [186]. Niclosamide induces cytoplasmic acidification, leading to mTORC1 indirect inhibition, through its protonophoric/proton gradient regulator properties [187].…”

Section: Small Molecule Enhancers Of Rapamycin (Smers)mentioning

confidence: 98%

Targeting Unselective Autophagy of Cellular Aggregates

Seneci

2015

Chemical Modulators of Protein Misfolding and Neurodegenerative Disease

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“…RSV is comprised of a number of polypheinolic compounds, including curcumin (111), rottlerin (112), genistein (113) and quercetin (114,115). RSV has been purported to be of potential use in cancer treatment and evidence indicates that it may inhibit pathways contributing to cell proliferation (116).…”

Section: Resveratrol As a Chemopreventivementioning

confidence: 99%

Resveratrol (3,5,4′-trihydroxystilbene) and its properties in oral diseases

Perrone

Fuggetta

Ardito

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Health promotion strategies and lifestyle changes are important in disease prevention. Oral health has received a large amount of attention previously as it is a fundamental component of general health and it contributes to the quality of life. Therefore, the study of associations between diet, health and the presence of bioactive compounds in food is receiving a substantial amount of attention. In the present review the effects and targets of a natural polyohenolic stilbenoid compound; resveratrol (3,5,4'-trihydroxystilbene; RSV) is assessed, and the future prospects for RSV in promoting oral health are considered. RSV is a phytoalexin, synthesized by a wide range of plants and abundantly extracted in grape skin, it has been purported to exert a multiplicity of anti-inflammatory, anti-viral, anti-microbial, estrogenic, anticancer, cardioprotective, neuroprotective and immunomodulatory functions. In this review, following an introduction documenting the biochemistry of RSV and RSV glucosides, the bioavailability and pharmacokinetics of RSV are described. Considering its multiple properties, the present review has focused on the potential benefits of RSV as an antioxidant and chemopreventive agent.

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Rottlerin and Cancer: Novel Evidence and Mechanisms

Cited by 67 publications

References 91 publications

Silencing of TGM2 reverses epithelial to mesenchymal transition and modulates the chemosensitivity of breast cancer to docetaxel

Silencing of TGM2 reverses epithelial to mesenchymal transition and modulates the chemosensitivity of breast cancer to docetaxel

Targeting Unselective Autophagy of Cellular Aggregates

Resveratrol (3,5,4′-trihydroxystilbene) and its properties in oral diseases

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