Cyclodextrin‐induced apoptosis in human keratinocytes is caspase‐8 dependent and accompanied by mitochondrial cytochrome <i>c</i> release

Schönfelder, Ute; Radestock, Anja; Elsner, Peter; Hipler, Uta‐Christina

doi:10.1111/j.1600-0625.2006.00481.x

Cited by 33 publications

(24 citation statements)

References 53 publications

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“…This is because there was a report that MBCD could induce apoptosis in human keratinocytes [16], while HPBCD does not have that effect [9]. Furthermore, when administered orally, absorption of HPBCD is better than that of MBCD [8].…”

Section: Dg-bcd-abt Caused Tumor Regression In Micementioning

confidence: 99%

Targeting cholesterol with β‐cyclodextrin sensitizes cancer cells for apoptosis

2015

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We found that targeting cholesterol with beta‐cyclodextrin (bCD) and its derivatives disrupted signal transduction between PI3K and AKT, attenuating AKT pro‐survival signals. In their absence, 2‐deoxyglucose (2DG) caused anti‐apoptotic protein Mcll to dissociate from pro‐apoptotic Bak at mitochondria. Normally Bak is sequestered by its inhibitory associations with Mcll and Bcl‐xL, and only when Bak is released from both, is it free to form oligomers through which cytochrome c can escape into the cytosol. Thus an addition of a bcl‐2 antagonist dissociates Bak from Bcl‐xL, triggering cytochrome c release and inducing apoptosis. 2DG–bCD can also sensitize type II cancer cells for TRAIL‐mediated apoptosis.

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Section: Dg-bcd-abt Caused Tumor Regression In Micementioning

confidence: 99%

Targeting cholesterol with β‐cyclodextrin sensitizes cancer cells for apoptosis

2015

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“…8 ). These findings may provide further rational use of cyclodextrins in topical formulations for dermal and transdermal drug delivery, or textiles for medical applications [19] .…”

Section: Measurement Of Biocompatibility and Cytotoxicitymentioning

confidence: 99%

Evaluation of Biocompatibility and Cytotoxicity Using Keratinocyte and Fibroblast Cultures

Wiegand¹,

Hipler²

2009

Skin Pharmacol Physiol

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Determination of biocompatibility and cytotoxicity is part of the initial evaluation of medical devices stipulated by ISO standards on biological evaluation of medical devices. Cell culture systems for testing biological reactions to drugs, biomaterials or treatment techniques used in various disciplines have been gaining importance. A wide variety of cell lines are commonly used: cultured fibroblasts from human skin, buccal mucosa, periodontal membrane or embryonic lung; epithelial and HeLa cells; cultures of human keratinocytes and HaCaT cells; different murine cell lines (C3H-L, Balb/c 3T3, L929 and others) as well as murine cells cultured from liver and spleen; T lymphocytes from lymph nodes and macrophages obtained by lavage. All these cells are suitable for the use in biocompatibility tests. Nevertheless, the general opinion is that cytotoxicity tests in vitro will be more convincing when performed with cells that are homologous with the human tissue concerned. In accordance, appropriate cell lines for the use in cytotoxicity and tolerance tests concerning the skin would be human dermal fibroblasts and human epidermal keratinocytes, as they take an active part in the immune response, inflammatory processes and wound healing.

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“…It is reported that β-CD and M-β-CD induce caspasedependent apoptotic cell death in human keratinocytes on depletion of membrane cholesterol, whereas α-CD, γ-CD, and HP-β-CD are not apoptotic to this type of cell (Schönfelder et al, 2006).…”

Section: What Is the Safety Record Of Cyclodextrins?mentioning

confidence: 99%

Cyclodextrins

Stella

He²

2008

Toxicol Pathol

629

415

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β-cyclodextrin (β-CD) and other cyclodextrins (CDs) have utility for solubilizing and stabilizing drugs; however, some are nephrotoxic when administered parenterally. A number of workers have attempted to identify, prepare, and evaluate various CD derivatives with superior inclusion complexation and maximal in vivo safety for various biomedical uses. A systematic study led to SBE-β-CD (Captisol), a polyanionic variably substituted sulfobutyl ether of β-CD, as a non-nephrotoxic derivative and HP-β-CD, a modified CD developed by Janssen. SBE-β-CD and HP-β-CD have undergone extensive safety studies and are currently used in six products approved by the Food and Drug Administration (four for Captisol and two for HP-β-CD). They are also in use in numerous clinical and preclinical studies. This article will focus on the issues that led to the development of these two CDs, their safety, characterization, and applications, and especially their ability to improve drug delivery. SBE-β-CD interacts very well with neutral drugs to facilitate solubility and chemical stability, and because of its polyanionic nature, it interacts particularly well with cationic drugs. Complexes between SBE-β-CD and HP-β-CD and various drugs have been shown to rapidly dissociate after parenteral drug administration, to have no tissue-irritating effects after intramuscular dosing, and to result in superior oral bioavailability of poorly water-soluble drugs. The pharmacokinetics, tissue distribution, and cellular effects of some representative CDs, including SBE-β-CD and HP-β-CD, are reviewed. The safety profiles of CDs are discussed, with emphasis on the biological effects of some CDs on the gastrointestinal tract, kidney, and reproduction and development and the carcinogenic potential of CDs. In addition, human experience with CD derivatives, specifically SBE-β-CD and HP-β-CD, indicates that these two CDs are well tolerated in humans and have no adverse effects on the kidneys or other organs following either oral or intravenous administration.

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Cyclodextrin‐induced apoptosis in human keratinocytes is caspase‐8 dependent and accompanied by mitochondrial cytochrome c release

Cited by 33 publications

References 53 publications

Targeting cholesterol with β‐cyclodextrin sensitizes cancer cells for apoptosis

Targeting cholesterol with β‐cyclodextrin sensitizes cancer cells for apoptosis

Evaluation of Biocompatibility and Cytotoxicity Using Keratinocyte and Fibroblast Cultures

Cyclodextrins

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