Melanoma and the Dermatologist in the Third Millennium

MacKie, Rona M.

doi:10.1001/archderm.136.1.71

Cited by 11 publications

(2 citation statements)

References 7 publications

(5 reference statements)

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“…Despite recent advances in immunotherapy and vaccinotherapy, chemotherapy remains the standard therapeutic option for disseminated melanoma (Mackie, 2000). However, MM frequently displays primary chemoresistance, and only a few cytotoxic drugs have shown activity against this tumor.…”

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confidence: 99%

Cytotoxicity, DNA Damage, and Apoptosis Induced by New Fotemustine Analogs on Human Melanoma Cells in Relation to O⁶-Methylguanine DNA-Methyltransferase Expression

Passagne¹,

Evrard²,

Winum³

et al. 2003

J Pharmacol Exp Ther

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Fotemustine is a third generation chloroethylnitrosourea that has demonstrated significant antitumoral effects in malignant melanoma. However, its use is somewhat limited by its toxic side effects and chemoresistance caused by direct repair of O 6 -alkyl groups by the enzyme O 6 -methylguanine DNA-methyltransferase (MGMT). The aim of this work was to determine to what extent the expression of MGMT influences cytotoxicity, DNA damage, and apoptosis induced by new nitrososulfamide analogs of fotemustine (compounds 4 and 8), which have previously demonstrated interesting antiproliferative properties. We carried out complementary strategies that consisted of MGMT cDNA transfection in CAL77 MerϪ melanoma cells and of MGMT inhibition with O 6 -benzylguanine (BG) in A375 Merϩ melanoma cells. MGMT-transfected cells were 7 to 9 times less sensitive to fotemustine than parent cells, whereas no difference between the transfected and parent cells was observed for nitrososulfamide analogs. The cytotoxicity of these analogs vis à vis a MGMT-proficient A375 melanoma cell line was approximately 3 times greater than that of fotemustine. Coincubation of these cells with O 6 -benzylguanine significantly increased the cytotoxicity of fotemustine and compound 8, whereas BG had little effect on the cytotoxicity of compound 4. Furthermore, DNA fragmentation determined by a comet assay was greater with nitrososulfamide analogs than with fotemustine. O 6 -benzylguanine increased DNA fragmentation for fotemustine and compound 8, but not for compound 4, which induced comets with a typical apoptotic appearance. The ability of this compound to induce apoptosis in the absence of BG was confirmed by a specific enzyme-linked immunosorbent assay apoptotic assay using a single-stranded DNA monoclonal antibody.

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confidence: 99%

Cytotoxicity, DNA Damage, and Apoptosis Induced by New Fotemustine Analogs on Human Melanoma Cells in Relation to O⁶-Methylguanine DNA-Methyltransferase Expression

Passagne¹,

Evrard²,

Winum³

et al. 2003

J Pharmacol Exp Ther

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“…Thus, multidrug resistance has been frequently observed in such cases, hence, new drugs with novel modes of action might help to increase the sensitivity of melanoma to chemotherapeutic treatments. 59 Since diospyrin analogues are known to induce apoptosis in several human cancer cell lines, it would be relevant to explore the mechanism of action of its glycosides in this respect. 34 Further, involvement of a ROS-mediated pathway was established, 35 revealing dramatic changes in mitochondrial transmembrane potential and other associated events signaling apoptotic cell death, in MCF-7 cells, caused by diospyrin diethyl ether.…”

Section: Antitumor Activitymentioning

confidence: 99%

Novel glycoconjugates of diospyrin, a quinonoid plant product: synthesis and evaluation of cytotoxicity against human malignant melanoma (A375) and laryngeal carcinoma (Hep2)

et al. 2007

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Glycoside derivatives of diospyrin (1) were synthesized for the first time, and the cytotoxicity of the novel compounds vis-à-vis their precursors were evaluated against two human cancer cell lines, viz. malignant melanoma (A375) and laryngeal carcinoma (Hep2). The IC(50) values were in the low micromolar range for all the compounds tested, and A375 cells showed comparatively greater sensitivity than Hep2. Most of the compounds exhibited enhanced activity as compared to the plant-derived quinonoid precursor of the series (1), while the aminophenyl mannosyl (6) was found to be the most effective derivative. In A375 cells, 6 (IC(50) = 0.02 microM) showed the maximum increase in cytotoxicity (approximately 35-fold) over that of 1 (IC(50) = 0.82 microM). Again, when the glycosides were evaluated at a given concentration (0.1 microM) for their relative capacity to generate ROS from A375 cells, the compound 6 could produce the highest amount of ROS. Incidentally, this derivative also showed a comparatively lower toxicity (IC(50) approximately 41 microM) when tested against normal human peripheral blood mononuclear cells, indicating a fair prospect of its development as a novel chemotherapeutic agent for the treatment of malignant melanoma.

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Melanoma

Plaza¹,

Prieto²

2017

Pathology of Pigmented Skin Lesions

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Melanoma and the Dermatologist in the Third Millennium

Cited by 11 publications

References 7 publications

Cytotoxicity, DNA Damage, and Apoptosis Induced by New Fotemustine Analogs on Human Melanoma Cells in Relation to O⁶-Methylguanine DNA-Methyltransferase Expression

Cytotoxicity, DNA Damage, and Apoptosis Induced by New Fotemustine Analogs on Human Melanoma Cells in Relation to O⁶-Methylguanine DNA-Methyltransferase Expression

Novel glycoconjugates of diospyrin, a quinonoid plant product: synthesis and evaluation of cytotoxicity against human malignant melanoma (A375) and laryngeal carcinoma (Hep2)

Melanoma

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Melanoma and the Dermatologist in the Third Millennium

Cited by 11 publications

References 7 publications

Cytotoxicity, DNA Damage, and Apoptosis Induced by New Fotemustine Analogs on Human Melanoma Cells in Relation to O6-Methylguanine DNA-Methyltransferase Expression

Cytotoxicity, DNA Damage, and Apoptosis Induced by New Fotemustine Analogs on Human Melanoma Cells in Relation to O6-Methylguanine DNA-Methyltransferase Expression

Novel glycoconjugates of diospyrin, a quinonoid plant product: synthesis and evaluation of cytotoxicity against human malignant melanoma (A375) and laryngeal carcinoma (Hep2)

Melanoma

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Cytotoxicity, DNA Damage, and Apoptosis Induced by New Fotemustine Analogs on Human Melanoma Cells in Relation to O⁶-Methylguanine DNA-Methyltransferase Expression

Cytotoxicity, DNA Damage, and Apoptosis Induced by New Fotemustine Analogs on Human Melanoma Cells in Relation to O⁶-Methylguanine DNA-Methyltransferase Expression