Development of a Novel Experimental In Vitro Model of Isothiocyanate-induced Apoptosis in Human Malignant Melanoma Cells

Mantso, Theodora, Sfakianos, Aristeidis, Atkinson, Aithne, Anestopoulos, Ioannis, Mitsiogianni, Melina, Botaitis, Sotirios, Perente, Sebachedin, Simopoulos, Constantinos, Vasileiadis, Stavros, Franco, Rodrigo, Pappa, Aglaia and Panagiotidis, Mihalis (2016) Development of a Novel Experimental In Vitro Model of Isothiocyanate-induced Apoptosis in Human Malignant Melanoma Cells. Anticancer Research, 36 (12). pp. 6303-6310. ISSN 0250-7005

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Background: Isothiocyanates are constituents of cruciferous vegetables which have been associated with reduced cancer risk partially through their ability to induce apoptosis in malignant cells including melanoma.

Materials and Methods: We have utilized human malignant melanoma (A375), epidermoid carcinoma (A431) and immortalized keratinocyte (HaCaT) cells exposed to various isothiocyanates, under different experimental conditions.

Results: An experimental in vitro model utilizing low isothiocyanate concentrations (0.1-5 μM for 48 h with all treatments being refreshed after 24h) was shown to be (i) most efficient in exerting an anti-cancer effect when compared to higher concentrations (5-100 μM for 24 or 48 h added as a single bolus) and (ii) specific to A375 cells while A431 and HaCaT cells remained unaffected. Such effect involved the activation of several caspases including (iii) initiator caspases 8, 9, 4 (indicating the involvement of intrinsic, extrinsic and endoplasmic reticulum-based pathways) and (iv) effector caspases 3, 7 and 6.

Conclusion: Utilization of low isothiocyanate concentrations (under the conditions described herein) exerts an anti-cancer effect specific to human malignant melanoma cells thus providing a therapeutic basis for their utilization in management of the disease.

Item Type: Article
Additional Information: Funding infromation: This work was supported, in part, by a Heriot Watt University (HWU, Edinburgh, UK) and Northumbria University (NNU, Newcastle upon Tyne, UK) start-up funds (Professor Mihalis Panayiotidis) including a HWU (Mrs Theodora Mantso) and a NNU (Mrs Melina Mitsiogianni) PhD studentship and by a LLP Erasmus Programme (Mr Aris Sfakianos and Dr Aglaia Pappa). Furthermore, the Authors would like to thank Dr Sharon Broby (Dermal Toxicology and Effects Group; Centre for Radiation, Chemical and Environmental Hazards; Public Health England, UK) for kindly providing the human keratinocyte (HaCaT) cell line.
Uncontrolled Keywords: Isothiocyanates, sulforaphane, phenethyl isothiocyanate, benzyl isothiocyanate, malignant melanoma, apoptosis
Subjects: B100 Anatomy, Physiology and Pathology
C400 Genetics
Department: Faculties > Health and Life Sciences > Applied Sciences
Depositing User: Becky Skoyles
Date Deposited: 19 Jan 2017 08:44
Last Modified: 18 Nov 2021 16:00

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