Development of a novel experimental in vitro model of isothiocyanate-induced apoptosis in human malignant melanoma cells

Theodora Mantso, Aristeidis P. Sfakianos, Aithne Atkinson, Ioannis Anestopoulos, Melina Mitsiogianni, Sotirios Botaitis, Sebachedin Perente, Constantinos Simopoulos, Stavros Vasileiadis, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)6303-6309
Number of pages7
JournalAnticancer Research
Issue number12
Publication statusPublished - 1 Dec 2016


  • Apoptosis
  • Benzyl isothiocyanate
  • Isothiocyanates
  • Malignant melanoma
  • Phenethyl isothiocyanate
  • Sulforaphane

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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