HSP70 inhibition by 2-phenylethynesulfonamide induces lysosomal cathepsin D release and immunogenic cell death in primary effusion lymphoma

Granato, Marisa; Lacconi, Valentina; Peddis, M; Lotti, Lavinia Vittoria; Renzo, Livia Di; Gonnella, Roberta; Santarelli, Roberta; Trivedi, Pankaj; Frati, Luigi; D’Orazi, Gabriella; Faggioni, Alberto; Cirone, Mara

doi:10.1038/cddis.2013.263

Cited by 79 publications

(79 citation statements)

References 44 publications

(65 reference statements)

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“…It has recently been described that a vicious circle of ROS-induced zinc release and zinc-driven mitochondrial ROS production is an important neuronal cell death mechanism 50 . On the other hand, it has been reported that the induction of a type of cell death other than apoptosis in cancer cells might increase the immunogenic potential of cell death 51,52 . Whether a change in the death process upon Zn (II) pre-exposure can affect the immune response to UV-damaged cells, which would impact the development of various pathologies, e.g., autoimmunity or cancers, must be further studied.…”

Section: Discussionmentioning

confidence: 99%

Effects of non-toxic zinc exposure on human epidermal keratinocytes

et al. 2015

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Zinc is an essential microelement; its importance to skin is shown by severe skin symptoms in hereditary or acquired zinc deficiency, by the improvement of several skin conditions using systemic or topical zinc preparations and by the induced intracellular zinc release upon UVB exposure, which is the main harmful environmental factor to skin. Understanding the molecular background of the role of zinc in skin may help to gain insight into the pathology of skin disorders and to provide evidence for the therapeutic usefulness of zinc supplementation.Herein, we studied the effect of zinc chloride (ZnCl 2 ) exposure on the function of HaCaT keratinocytes, and we found that a non-toxic elevation in the concentration of extracellular zinc (100 µM) facilitated cell proliferation and induced significant alterations in the mRNA expression of NOTCH1, IL8, and cyclooxygenase-2. In addition, we detected increased heme oxygenase-1 (HMOX1) expression and non-toxic generation of superoxide in the first 4 h.Regarding the effect on UVB-induced toxicity, although the level of cyclobutane pyrimidine dimers in keratinocytes pre-treated with zinc for 24 h was reduced 3 h after UVB irradiation, we found significantly enhanced superoxide generation 10 h after UVB exposure in the zinc pre-exposed cells. The overall survival was unaffected; however, there was a decrease in the percentage of early apoptotic cells and an increase in the percentage of late apoptotic plus necrotic cells.Our results suggest that exposure of human keratinocytes to non-toxic concentrations of ZnCl 2 impacts gene expression, cell proliferation and the response to environmental stress in skin. It would be important to further examine the role of zinc in skin and to further clarify if this issue can affect our thinking about the pathogenesis of skin diseases.

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Section: Discussionmentioning

confidence: 99%

Effects of non-toxic zinc exposure on human epidermal keratinocytes

et al. 2015

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“…Next, we investigated whether, besides ATG5, the increased CAPN activity would lead to the cleavage of other molecules such as BID, [56][57][58] whose truncated fragments have been reported to promote cell death. 59,60 Western blot analysis revealed the appearance of a BID-cleaved form in KSHV-infected and starved THP-1 cells that was not detectable in the presence of PD (Fig. 2E).…”

Section: Kshv-infected Cells Was Evaluated 30 H Post-infection By Immmentioning

confidence: 99%

KSHV reduces autophagy in THP-1 cells and in differentiating monocytes by decreasing CAST/calpastatin and ATG5 expression

et al. 2016

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We have previously shown that Kaposi sarcoma-associated herpesvirus (KSHV) impairs monocyte differentiation into dendritic cells (DCs). Macroautophagy/autophagy has been reported to be essential in such a differentiating process. Here we extended these studies and found that the impairment of DC formation by KSHV occurs through autophagy inhibition. KSHV indeed reduces CAST (calpastatin) and consequently decreases ATG5 expression in both THP-1 monocytoid cells and primary monocytes. We unveiled a new mechanism put in place by KSHV to escape from immune control. The discovery of viral immune suppressive strategies that contribute to the onset and progression of viral-associated malignancies is of fundamental importance for finding new therapeutic approaches against them.

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“…There are also some evidences that several chemicals, such as benzylidene lactam, triptolide, emunine etc., inhibit hsp gene expressions by interacting with HSFs [108]. It is known that 2-phenylethynesulfonamide (PES, pifitrin-) is a specific inhibitor of stress-inducible HSP70, the usage of PES induces cell death in primary effusion lymphoma [127].…”

Section: Hsp Inhibition and Clinical Trialsmentioning

confidence: 99%

Heat Shock Proteins and Cancer: Plant Based Therapy

Uçar

2015

Heat Shock Proteins

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Cancer is one of the major causes of mortality in the world. Each year approximately 13 million people suffer from cancer disease, and approximately 60 % of them die because of cancer. Besides most of the patients response harmful side effects of chemo-and radiotherapies. Therefore the establishment of new therapeutic strategies for the treatment of cancers will be required. A number of studies have shown that some HSP are induced in specific tumor cells. For example, increased levels of HSP105, HSP90, HSP70, HSP60, HSP27 have been detected in colon cancer, lung cancer, hepatocellular carcinoma, colorectal cancer, and gliomas, respectively. Elevated HSP levels in tumor cells are suggested to be responsible for increased chemotherapy resistance and poor prognosis. Suppression of HSP expressions in cancer cells is a new strategy for the treatment. It is well known that some plant extracts and their flavonoids significantly decrease HSP expression, and induce apoptosis of cancer cells. In addition, using of the HSP inhibitors in association with classical chemotherapy increases the sensitivity of cancer cells to the cytotoxic drugs. Therefore, some plants and their biologically active natural compounds have been investigated for their possible contribution to cancer therapy. The current chapter reviews the role of HSP in different cancer types and suppressing HSP with some natural products.

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HSP70 inhibition by 2-phenylethynesulfonamide induces lysosomal cathepsin D release and immunogenic cell death in primary effusion lymphoma

Cited by 79 publications

References 44 publications

Effects of non-toxic zinc exposure on human epidermal keratinocytes

Effects of non-toxic zinc exposure on human epidermal keratinocytes

KSHV reduces autophagy in THP-1 cells and in differentiating monocytes by decreasing CAST/calpastatin and ATG5 expression

Heat Shock Proteins and Cancer: Plant Based Therapy

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