Lovastatin and valproic acid additively attenuate cell invasion in ACC-MESO-1 cells

Yamauchi, Yoshikane; Izumi, Yuichi; Asakura, Keisuke; Fukutomi, Toshinori; Serizawa, Akihiko; Kawai, Kenji; Wakui, Masatoshi; Suematsu, Makoto

doi:10.1016/j.bbrc.2011.05.149

Cited by 9 publications

(7 citation statements)

References 22 publications

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“…The therapeutic potential of statins for suppressing mesothelioma cell growth has been reported in vitro and in mouse xenografts [ 106 , 107 ]. Furthermore, statins are suggested to have synergistic or additive antitumor effects when used with other drugs [ 108 , 109 , 110 ]. Recently, it was reported that mesothelioma cells with NF2 and/or LATS2 mutations were more sensitive to fluvastatin compared to those with BAP1 mutations [ 111 ], whereas merlin-negative breast cancer cells showed sensitivity to simvastatin [ 112 ].…”

Section: Potential Molecular Targets In Merlin-negative Mesotheliomentioning

confidence: 99%

NF2/Merlin Inactivation and Potential Therapeutic Targets in Mesothelioma

Sato

Sekido

2018

IJMS

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The neurofibromatosis type 2 (NF2) gene encodes merlin, a tumor suppressor protein frequently inactivated in schwannoma, meningioma, and malignant mesothelioma (MM). The sequence of merlin is similar to that of ezrin/radixin/moesin (ERM) proteins which crosslink actin with the plasma membrane, suggesting that merlin plays a role in transducing extracellular signals to the actin cytoskeleton. Merlin adopts a distinct closed conformation defined by specific intramolecular interactions and regulates diverse cellular events such as transcription, translation, ubiquitination, and miRNA biosynthesis, many of which are mediated through Hippo and mTOR signaling, which are known to be closely involved in cancer development. MM is a very aggressive tumor associated with asbestos exposure, and genetic alterations in NF2 that abrogate merlin’s functional activity are found in about 40% of MMs, indicating the importance of NF2 inactivation in MM development and progression. In this review, we summarize the current knowledge of molecular events triggered by NF2/merlin inactivation, which lead to the development of mesothelioma and other cancers, and discuss potential therapeutic targets in merlin-deficient mesotheliomas.

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Section: Potential Molecular Targets In Merlin-negative Mesotheliomentioning

confidence: 99%

NF2/Merlin Inactivation and Potential Therapeutic Targets in Mesothelioma

Sato

Sekido

2018

IJMS

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“…Lovastatin [109] was shown to decrease cell viability in a dose-dependent manner in human MPM cell lines, through apoptosis induction. In addition, the combination of lovastatin and valproate was shown to reduce cell invasion of Acc-Meso-1, a human-derived MPM cell line [110]. HWANG et al [51] reported a synergistic effect of the combination of pemetrexed and simvastatin on apoptosis induction in MSTO-211 MPM cells by reactive oxygen [43] Inhibition of angiogenesis [44] Inhibition of invasion and metastasis [45] Induction of tumour differentiation [46] Reversion of multidrug resistance [47] Phase III: gastric cancer [48], colorectal cancer [49] Phase III: ongoing in SCLC [50] Preclinical [47,[51][52][53] Itraconazole Antifungal Induction of angiogenesis [54] Inhibition of hedgehog pathway [8] Phase II: NSCLC [55] Prostate cancer [56] Basal cell carcinoma [57] Preclinical [58] Arsenic trioxide Preclinical [52,85,88] Thalidomide Sickness in pregnant females (withdrawn) [29] Inhibition of angiogenesis [31] Inhibition of cell proliferation [32] Immunomodulatory function [33] FDA approved: multiple myeloma [34] Phase III [37] Anisomycin Antibiotic Induction of apoptosis [89] Preclinical [90] Preclinical [90]…”

Section: Statinsmentioning

confidence: 99%

Drug repurposing in malignant pleural mesothelioma: a breath of fresh air?

et al. 2018

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Drug repurposing is the use of known drugs for new indications. Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. So far, few treatments have been approved in this disease. However, its incidence is expected to increase significantly, particularly in developing countries. Consequently, drug repurposing appears as an attractive strategy for drug development in MPM, since the known pharmacology and safety profile based on previous approvals of repurposed drugs allows for faster time-to-market for patients and lower treatment cost. This is critical in low- and middle-income countries where access to expensive drugs is limited. This review assesses the published preclinical and clinical data about drug repurposing in MPM.In this review, we identified 11 therapeutic classes that could be repositioned in mesothelioma. Most of these treatments have been evaluated , half have been evaluated in animal models of MPM and only three ( valproate, thalidomide and zoledronic acid) have been investigated in clinical trials, with limited benefits so far. Efforts could be coordinated to pursue further investigations and test promising drugs identified in preclinical experiments in appropriately designed clinical trials.

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“…Moreover, it has been used as an anticonvulsant and a mood-stabilizing drug, similar to lithium, and also has neuroprotective effects in neurodegenerative conditions [14,15,16,17]. VPA was recognized as a hepatotoxic drug [18,19]; additionally, several studies have demonstrated that VPA treatment led to growth inhibition or apoptosis or both in a range of cancer cells [20,21,22,23], including HCC cells [24,25,26]. As a HDAC inhibitor, VPA can prompt the differentiation of various cancer cells in vitro and prevent tumor progression and metastasis in vivo [27].…”

Section: Introductionmentioning

confidence: 99%

Valproic Acid Induces Endocytosis-Mediated Doxorubicin Internalization and Shows Synergistic Cytotoxic Effects in Hepatocellular Carcinoma Cells

Saha

Yin

Kim

et al. 2017

IJMS

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Valproic acid (VPA), a well-known histone deacetylase (HDAC) inhibitor, is used as an anti-cancer drug for various cancers, but the synergistic anti-cancer effect of VPA and doxorubicin (DOX) combination treatment and its potential underlying mechanism in hepatocellular carcinoma (HCC) remain to be elucidated. Here, we evaluate the mono- and combination-therapy effects of VPA and DOX in HCC and identify a specific and efficient, synergistic anti-proliferative effect of the VPA and DOX combination in HCC cells, especially HepG2 cells; this effect was not apparent in MIHA cells, a normal hepatocyte cell line. The calculation of the coefficient of drug interaction confirmed the significant synergistic effect of the combination treatment. Concurrently, the synergistic apoptotic cell death caused by the VPA and DOX combination treatment was confirmed by Hoechst nuclear staining and Western blot analysis of caspase-3 and poly (ADP-ribose) polymerase (PARP) activation. Co-treatment with VPA and DOX enhanced reactive oxygen species (ROS) generation and autophagy, which were clearly attenuated by ROS and autophagy inhibitors, respectively. Furthermore, as an indication of the mechanism underlying the synergistic effect, we observed that DOX internalization, which was induced in the VPA and DOX combination-treated group, occurred via by the caveolae-mediated endocytosis pathway. Taken together, our study uncovered the potential effect of the VPA and DOX combination treatment with regard to cell death, including induction of cellular ROS, autophagy, and the caveolae-mediated endocytosis pathway. Therefore, these results present novel implications in drug delivery research for the treatment of HCC.

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Lovastatin and valproic acid additively attenuate cell invasion in ACC-MESO-1 cells

Cited by 9 publications

References 22 publications

NF2/Merlin Inactivation and Potential Therapeutic Targets in Mesothelioma

NF2/Merlin Inactivation and Potential Therapeutic Targets in Mesothelioma

Drug repurposing in malignant pleural mesothelioma: a breath of fresh air?

Valproic Acid Induces Endocytosis-Mediated Doxorubicin Internalization and Shows Synergistic Cytotoxic Effects in Hepatocellular Carcinoma Cells

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