Effect of dicarboxylic acids on normal human melanocytes in dispersed tissue culture*

Breathnach, A. S.; Martin, Bruce D.; Porro, M. Nazzaro; Passi, S.; Mann, Patricia R.; Cooper, Jennifer L.; Morpurgo, G.

doi:10.1111/j.1365-2133.1979.tb05642.x

Cited by 24 publications

(6 citation statements)

References 4 publications

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“…A functional, i.e. Clearly, differences in technique can influence results in tissue culture carried out in different laboratories, and Schachtschabel's observation is important in demonstrating an inhibitory effect of azelaic acid on melanoma cells in culture at concentrations which can, in fact, be effectively achieved by topical application of a 20",, cream to lesions of melasma and lentigo mahgna, with positive effect (Nazzaro-Porro et al, 1979. Schachtschabel (1984) has shown that concentrations of 1-3 X 10" ^ M azelaic acid significantly inhibit growth of Harding-Passey melanoma cells cultured with serum-free media.…”

Section: Discussionmentioning

confidence: 99%

“…This difference in reactivity between normal and abnormal cells appeared to be borne out by the demonstration that melanocytes in mixed cultures of epidermal cells were not damaged ultrastructurally by exposure to azelaic or dodecanedioic acids at a concentration of 10 ^ M (Breathnach et aL, 1979). This difference in reactivity between normal and abnormal cells appeared to be borne out by the demonstration that melanocytes in mixed cultures of epidermal cells were not damaged ultrastructurally by exposure to azelaic or dodecanedioic acids at a concentration of 10 ^ M (Breathnach et aL, 1979).…”

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confidence: 99%

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Ultrastructural observations on the effect of azelaic acid on normal human melanocytes and a human melanoma cell line in tissue culture

Robins¹,

Breathnach²,

Bennett

et al. 1985

Br J Dermatol

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Azelaic acid has been shown clinically to have a cytotoxic effect on the abnormally active and malignant human melanocyte, but it has no apparent effect upon normal melanocytes. This difference in reactivity between normal and abnormal cells in vivo is further examined here in vitro. The disodium salt of azelaic acid (C(9)2Na) was added to pure and mixed cultures of normal human melanocytes and to cultured human melanoma cells, at 10(-3) M, 10(-2) M, 5 X 10(-2) M, and 10(-1) M for 1 and 6 h. Control cultures and cultures exposed to the same concentrations of the disodium salt of adipic acid (C(6)2Na) were also examined. No damage to cells of any line was observed with diacids at 10(-3) M or 10(-2) M up to 6 h. At 5 X 10(-2) M some mitochondria of melanoma cells appeared swollen. With C(6)2Na at 10(-1) M for I and 6 h, minimal swelling of mitochondria was observed in some cells of all lines. Pure normal melanocytes and melanocytes of mixed cultures exhibited greater swelling of mitochondria with 10(-1) M C(9)2Na at 1 and 6 h, but the mitochondria of the malignant melanocytes were massively swollen with destruction of cristae. Plasma and nuclear membranes and membranes of rough endoplasmic reticulum were intact, but Golgi membranes exhibited vesiculation. These results provide further evidence that azelaic acid damages the human malignant melanocyte and that one of its targets is the mitochondrion. Damage to normal melanocytes, found here, may be due to the fact that, in culture, they are more active than in intact epidermis.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Ultrastructural observations on the effect of azelaic acid on normal human melanocytes and a human melanoma cell line in tissue culture

Robins¹,

Breathnach²,

Bennett

et al. 1985

Br J Dermatol

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“…On 13 December 1979 the lesion had increased greatly in size. Exenteration refused: Reviewed until 11 September 1980, when course of azelaic acid started. After 1 month her creatinine kinase was elevated and she became hypokalaemic.…”

Section: Methodsmentioning

confidence: 99%

Azelaic acid in the treatment of ocular and adnexal malignant melanoma.

Willshaw¹,

Rubinstein²

1983

British Journal of Ophthalmology

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SUMMARY Following reports of the successful management of cutaneous malignant melanoma with azelaic acid both locally and systemically a trial was undertaken to assess its value in the treatment of similar lesions involving the eye and its adnexa. Systemically administered azelaic acid failed to influence the melanomata in any of the 4 patients included in the study. A plea is made for the reporting even of such disappointing results in the present uncertain climate.The recent suggestion that enucleation of eyes harbouring malignant melanoma could precipitate dissemination of the tumour' has provoked considerable debate as to the best management of such eyes. 2 While it is recognised that ocular melanomata grow slowly in comparison with their cutaneous counterparts,2 nevertheless two independent followup studies on patients refusing enucleation have shown 100% of deaths from metastases.4" To many ophthalmologists, therefore, simply observing such lesions would be an unacceptable approach.In this climate of uncertainty reports of a chemotherapeutic agent cytotoxic to cutaneous melanomata6 stimulated us to investigate its efficacity in ocular and adnexal malignant melanoma. We report our results in treating 4 patients with azelaic acid. Patients and methodsAll 4 patients were attending the Medical Ophthalmology Clinic at the Birmingham and Midland Eye Hospital and had either refused surgical intervention or, after detailed explanation, requested a trial with this agent prior to surgery. The diagnosis ofmalignant melanoma was agreed by the referring ophthalmologist and both authors prior to entry into the study. Detailed informed consent and a full medical history, with specific attention being paid to gastrointestinal, genitourinary, and dermatological symptoms, were obtained.

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“…It was first described by Nazzaro-Porro and Passi [7 ]in the 1970s, and its effectiveness was first observed in hyperpigmentation. This finding was followed by evidence of its efficacy in acne vulgaris [8,9]. The mechanism of action of AzA against acne includes at least three described pharmacological effects: an anti-inflammatory effect, a stabilizing effect on the differentiation of keratinocytes in the follicular infundibulum, and an antimicrobial effect on various microorganisms including P. acnes and Staphylococcus epidermidis .…”

Section: Introductionmentioning

confidence: 99%

Azelaic Acid in the Treatment of Acne in Adult Females: Case Reports

Vargas-Díez

Hofmann²,

Bravo³

et al. 2013

Skin Pharmacol Physiol

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Acne, one of the most common skin problems in dermatological practice, is a condition that affects not only adolescents but also adults. While approximately 80% of cases occurring in adulthood are persistent from teenage years, around 20% are described as ‘late-onset' disease, appearing for the first time in adulthood. The disease can be triggered by hormonal changes (including a change from one contraceptive to another), or it can be induced by certain nonhormonal medications, emotional stress, and various underlying diseases such as polycystic ovary syndrome. In many cases acne becomes a chronic skin condition with undulating activity, including improvement and relapse phases, and is often experienced as a major psychological burden. It is, therefore, even more important to provide an effective as well as a safe and tolerable treatment. The spectrum of topical acne treatments has expanded substantially in recent years and various topical medications are available, ranging from azelaic acid, antibiotics, retinoids and benzoyl peroxide to several fixed combinations of these active compounds. The following case collection illustrates how 15% azelaic acid gel, as a well-established monotherapy, can be successfully employed to treat mild-to-moderate forms of adult female acne.

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Effect of dicarboxylic acids on normal human melanocytes in dispersed tissue culture*

Cited by 24 publications

References 4 publications

Ultrastructural observations on the effect of azelaic acid on normal human melanocytes and a human melanoma cell line in tissue culture

Ultrastructural observations on the effect of azelaic acid on normal human melanocytes and a human melanoma cell line in tissue culture

Azelaic acid in the treatment of ocular and adnexal malignant melanoma.

Azelaic Acid in the Treatment of Acne in Adult Females: Case Reports

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