An investigation of the effects of dithranol-induced apoptosis in a human keratinocyte cell line

George, Suja E.; Anderson, Rosaleen J.; Haswell, Malcolm; Groundwater, Paul W.

doi:10.1111/jphp.12019

Cited by 13 publications

(13 citation statements)

References 39 publications

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“…In agreement with other reports we also found significant apoptosis-inducing effects of anthralin in vitro when using concentrations ! 1 mM [16,17]. By using HaCaT cells, anthralin treatment in vitro has been shown to disrupt mitochondrial membrane potential and to activate caspase-3 resulting in cell apoptosis [16,21].…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, nonlesional or healthy skin shows an increase in epidermal proliferation and increased numbers of infiltrating T lymphocytes and Langerhans cells in response to anthralin treatment [15]. Using 2D in vitro cultures with immortalized epithelial cell lines like HaCat cells, anthralin has been shown to inhibit cell proliferation and to induce cell death [16,17]. Anthralin has also been reported to induce oxidative stress and lipid peroxidation in keratinocytes [18,19].…”

Section: Introductionmentioning

confidence: 99%

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Anthralin modulates the expression pattern of cytokeratins and antimicrobial peptides by psoriatic keratinocytes

Holstein

Fehrenbacher

Brück

et al. 2017

Journal of Dermatological Science

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Anthralin modulates the expression pattern of cytokeratins and antimicrobial peptides by psoriatic keratinocytes

Holstein

Fehrenbacher

Brück

et al. 2017

Journal of Dermatological Science

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“…In this pathway, the activation of caspase molecules and their substrates is the central apoptotic event [37]. The externalization of phosphatidylserine, a phospholipid normally restricted to the inner leaflet of plasma membrane, is one of the earliest apoptotic events [38]. We therefore evaluated the efficacy of gefitinib by determining the levels of phosphatidylserine.…”

Section: Discussionmentioning

confidence: 99%

Des-Gamma-Carboxy Prothrombin (DCP) Antagonizes the Effects of Gefitinib on Human Hepatocellular Carcinoma Cells

Cui

Zhang²,

Chu³

et al. 2015

Cell Physiol Biochem

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Background/Aims: Des-gamma-carboxy prothrombin (DCP), an aberrant prothrombin produced by hepatocellular carcinoma (HCC) cells, is known as a marker for HCC. Recent studies indicated that high levels of DCP are associated with the malignant potential of HCC. In this study, we aimed to investigate the association of DCP with gefitinib treatment failure in HCC and whether DCP counteracts gefitinib-induced growth inhibition and apoptosis of HCC. Methods: The experiments were performed in HCC cell lines HepG2 and PLC/PRF/5. The effects of gefitinib on HCC in the presence or absence of DCP were evaluated by the 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl-tetrazolium bromide (MTT) assay. Apoptotic cells were identified by Annexin V-FITC/PI staining. Western blotting was performed to analyze the expressions of molecules related to the apoptotic caspase-dependent pathway and epidermal growth factor receptor (EGFR) pathway. Results: Gefitinib inhibited HCC cell proliferation and induced apoptosis in HCC cells. The effects of gefitinib on HCC cells were antagonized by DCP. In the presence of DCP, HCC cells were resistant to the gefitinib-induced inhibition of proliferation and stimulation of apoptosis. DCP prevented the activation of the apoptotic caspase-dependent pathway induced by gefitinib. These antagonistic effects of DCP also arose from its ability to up-regulate EGFR, c-Met and hepatocyte growth factor (HGF) in HCC cells. Conclusion: DCP antagonized gefitinib-induced HCC cell growth inhibition by counteracting apoptosis and up-regulating the EGFR pathway. High levels of DCP might thus lead to low response rates or possibly no response to gefitinib in patients with HCC.

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“…Topical anthralin (dithranol) reduced overexpression of BCL-x while increasing BAX in psoriatic skin [79], and induced Caspase 3/7 activation in keratinocytes [31]. Phototherapy down-regulated BCL2 expression in dermal lymphocytes [28].…”

Section: Proteins Involved In Apoptosismentioning

confidence: 99%

In silico database screening of potential targets and pathways of compounds contained in plants used for psoriasis vulgaris

et al. 2015

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Reviews and meta-analyses of clinical trials identified plants used as traditional medicines (TMs) that show promise for psoriasis. These include Rehmannia glutinosa, Camptotheca acuminata, Indigo naturalis and Salvia miltiorrhiza. Compounds contained in these TMs have shown activities of relevance to psoriasis in experimental models. To further investigate the likely mechanisms of action of the multiple compounds in these TMs, we undertook a computer-based in silico investigation of the proteins known to be regulated by these compounds and their associated biological pathways. The proteins reportedly regulated by compounds in these four TMs were identified using the HIT (Herbal Ingredients' Targets) database. The resultant data were entered into the PANTHER (Protein ANnotation THrough Evolutionary Relationship) database to identify the pathways in which the proteins could be involved. The study identified 237 compounds in the TMs and these retrieved 287 proteins from HIT. These proteins identified 59 pathways in PANTHER with most proteins being located in the Apoptosis, Angiogenesis, Inflammation mediated by chemokine and cytokine, Gonadotropin releasing hormone receptor, and/or Interleukin signaling pathways. All four TMs contained compounds that had regulating effects on Apoptosis regulator BAX, Apoptosis regulator Bcl-2, Caspase-3, Tumor necrosis factor (TNF) or Prostaglandin G/H synthase 2 (COX2). The main proteins and pathways are primarily related to inflammation, proliferation and angiogenesis which are all processes involved in psoriasis. Experimental studies have reported that certain compounds from these TMs can regulate the expression of proteins involved in each of these pathways.

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An investigation of the effects of dithranol-induced apoptosis in a human keratinocyte cell line

Abstract: This study has elucidated the dose- and time-response effects of dithranol-induced apoptosis in human keratinocytes in vitro.

Cited by 13 publications

References 39 publications

Anthralin modulates the expression pattern of cytokeratins and antimicrobial peptides by psoriatic keratinocytes

Anthralin modulates the expression pattern of cytokeratins and antimicrobial peptides by psoriatic keratinocytes

Des-Gamma-Carboxy Prothrombin (DCP) Antagonizes the Effects of Gefitinib on Human Hepatocellular Carcinoma Cells

In silico database screening of potential targets and pathways of compounds contained in plants used for psoriasis vulgaris

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