The histone deacetylase inhibitor trichostatin A reduces lysosomal pH and enhances cisplatin-induced apoptosis

Eriksson, Ida; Joosten, Maria; Roberg, Karin; Öllinger, Karin

doi:10.1016/j.yexcr.2012.10.004

Cited by 40 publications

(31 citation statements)

References 29 publications

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“…Apoptosis and angiogenesis are two potential targets for novel strategies to treat this disease (27). Resistance to radiotherapy and chemotherapy are common consequences of the dysregulation of apoptosis, therefore, inducing apoptosis is an important feature of various chemotherapy drugs, including temozolomide and cisplatin (28,29). Cap, the most abundant pungent chili pepper component, has been widely examined as an anti-cancer agent, and induces cell apoptosis in numerous cancer cell lines, in vitro and when explanted into rodents (11,30,31).…”

Section: Discussionmentioning

confidence: 99%

Capsaicin and dihydrocapsaicin induce apoptosis in human glioma cells via ROS and Ca2+-mediated mitochondrial pathway

Xie

Guang-hong

Tang

et al. 2016

Molecular Medicine Reports

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Human glioma is the most common type of primary brain tumor and one of the most invasive and aggressive tumors, which, even with treatments including surgery, radiotherapy and chemotherapy, often relapses and exhibits resistance to conventional treatment methods. Developing novel strategies to control human glioma is, therefore, an important research focus. The present study investigated the mechanism of apoptosis induction in U251 human glioma cells by capsaicin (Cap) and dihydrocapsaicin (DHC), the major pungent ingredients of red chili pepper, using the Cell Counting Kit-8 assay, transmission electron microscopy analysis, flow cytometry analysis, laser scanning confocal microscope analysis and immunohistochemical staining. Treatment of U251 glioma cells with Cap and DHC resulted in a dose- and time-dependent inhibition of cell viability and induction of apoptosis, whereas few effects were observed on the viability of L929 normal murine fibroblast cells. The apoptosis-inducing effects of Cap and DHC in U251 cells were associated with the generation of reactive oxygen species, increased Ca2+ concentrations, mitochondrial depolarization, release of cytochrome c into the cytosol and activation of caspase-9 and −3. These effects were further confirmed by observations of the anti-tumor effects of Cap and DHC in vivo in a U251 cell murine tumor xenograft model. These results demonstrate that Cap and DHC are effective inhibitors of in vitro and in vivo survival of human glioma cells, and provide the rationale for further clinical investigation of Cap and DHC as treatments for human glioma.

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Section: Discussionmentioning

confidence: 99%

Capsaicin and dihydrocapsaicin induce apoptosis in human glioma cells via ROS and Ca2+-mediated mitochondrial pathway

Xie

Guang-hong

Tang

et al. 2016

Molecular Medicine Reports

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“…244, 245, 246, 247 This raises the intriguing possibility that pharmacological inhibitors of DNA methyltransferases and histone deacetylases, some of which are currently approved by international regulatory agencies for use in cancer patients, may limit CDDP resistance at least in part by modulating the abundance of specific microRNAs. 247, 248, 249, 250, 251, 252 Robust experimental evidence in support of this hypothesis is lacking.…”

Section: Systems Biology and Cisplatin Resistancementioning

confidence: 99%

Systems biology of cisplatin resistance: past, present and future

Vitale²,

et al. 2014

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The platinum derivative cis-diamminedichloroplatinum(II), best known as cisplatin, is currently employed for the clinical management of patients affected by testicular, ovarian, head and neck, colorectal, bladder and lung cancers. For a long time, the antineoplastic effects of cisplatin have been fully ascribed to its ability to generate unrepairable DNA lesions, hence inducing either a permanent proliferative arrest known as cellular senescence or the mitochondrial pathway of apoptosis. Accumulating evidence now suggests that the cytostatic and cytotoxic activity of cisplatin involves both a nuclear and a cytoplasmic component. Despite the unresolved issues regarding its mechanism of action, the administration of cisplatin is generally associated with high rates of clinical responses. However, in the vast majority of cases, malignant cells exposed to cisplatin activate a multipronged adaptive response that renders them less susceptible to the antiproliferative and cytotoxic effects of the drug, and eventually resume proliferation. Thus, a large fraction of cisplatin-treated patients is destined to experience therapeutic failure and tumor recurrence. Throughout the last four decades great efforts have been devoted to the characterization of the molecular mechanisms whereby neoplastic cells progressively lose their sensitivity to cisplatin. The advent of high-content and high-throughput screening technologies has accelerated the discovery of cell-intrinsic and cell-extrinsic pathways that may be targeted to prevent or reverse cisplatin resistance in cancer patients. Still, the multifactorial and redundant nature of this phenomenon poses a significant barrier against the identification of effective chemosensitization strategies. Here, we discuss recent systems biology studies aimed at deconvoluting the complex circuitries that underpin cisplatin resistance, and how their findings might drive the development of rational approaches to tackle this clinically relevant problem.

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“…Incubation of CLL primary cells with fludarabine led to the lysosome integrity loss and cathepsin B release, which was further potentiated by the addition of valproic acid, a well-known histone deacetylase (HDAC) inhibitor that increased cathepsin B expression [60]. Similarly, cisplatin was also reported to induce cell death associated with LMP [61], whereas cisplatin resistance could be overcome by inducing LMP with CQ coincubation [91]. In addition, LMP was also attributed to the proteasome inhibitor, bortezomib, with a mechanism involving cathepsin-mediated caspase 2 activation [62].…”

Section: Lysosome-targeting Agents As Anticancer Drugsmentioning

confidence: 99%

Typical and Atypical Inducers of Lysosomal Cell Death: A Promising Anticancer Strategy

Domagała

Fidyt

Bobrowicz

et al. 2018

IJMS

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Lysosomes are conservative organelles with an indispensable role in cellular degradation and the recycling of macromolecules. However, in light of recent findings, it has emerged that the role of lysosomes in cancer cells extends far beyond cellular catabolism and includes a variety of cellular pathways, such as proliferation, metastatic potential, and drug resistance. It has been well described that malignant transformation leads to alterations in lysosomal structure and function, which, paradoxically, renders cancer cells more sensitive to lysosomal destabilization. Furthermore, lysosomes are implicated in the regulation and execution of cell death in response to diverse stimuli and it has been shown that lysosome-dependent cell death can be utilized to overcome apoptosis and drug resistance. Thus, the purpose of this review is to characterize the role of lysosome in cancer therapy and to describe how these organelles impact treatment resistance. We summarized the characteristics of typical inducers of lysosomal cell death, which exert its function primarily via alterations in the lysosomal compartment. The review also presents other anticancer agents with the predominant mechanism of action different from lysosomal destabilization, the activity of which is influenced by lysosomal signaling, including classical chemotherapeutics, kinase inhibitors, monoclonal antibodies, as well as photodynamic therapy.

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The histone deacetylase inhibitor trichostatin A reduces lysosomal pH and enhances cisplatin-induced apoptosis

Cited by 40 publications

References 29 publications

Capsaicin and dihydrocapsaicin induce apoptosis in human glioma cells via ROS and Ca2+-mediated mitochondrial pathway

Capsaicin and dihydrocapsaicin induce apoptosis in human glioma cells via ROS and Ca2+-mediated mitochondrial pathway

Systems biology of cisplatin resistance: past, present and future

Typical and Atypical Inducers of Lysosomal Cell Death: A Promising Anticancer Strategy

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