TY - JOUR
T1 - Development of a Novel Experimental In Vitro Model of Isothiocyanate-induced Apoptosis in Human Malignant Melanoma Cells
AU - Mantso, Theodora
AU - Sfakianos, Aristeidis
AU - Atkinson, Aithne
AU - Anestopoulos, Ioannis
AU - Mitsiogianni, Melina
AU - Botaitis, Sotirios
AU - Perente, Sebachedin
AU - Simopoulos, Constantinos
AU - Vasileiadis, Stavros
AU - Franco, Rodrigo
AU - Pappa, Aglaia
AU - Panagiotidis, Mihalis
N1 - 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.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - 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.
AB - 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.
KW - Isothiocyanates
KW - sulforaphane
KW - phenethyl isothiocyanate
KW - benzyl isothiocyanate
KW - malignant melanoma
KW - apoptosis
U2 - 10.21873/anticanres.11226
DO - 10.21873/anticanres.11226
M3 - Article
SN - 0250-7005
VL - 36
SP - 6303
EP - 6310
JO - Anticancer Research
JF - Anticancer Research
IS - 12
ER -
