An Evaluation of the Anti-Carcinogenic Response of Major Isothiocyanates in Non-Metastatic and Metastatic Melanoma Cells

Melina Mitsiogianni; Sotiris Kyriakou; Ioannis Anestopoulos; Dimitrios T Trafalis; Maria V Deligiorgi; Rodrigo Franco; Aglaia Pappa; Mihalis I Panayiotidis

doi:10.3390/antiox10020284

An Evaluation of the Anti-Carcinogenic Response of Major Isothiocyanates in Non-Metastatic and Metastatic Melanoma Cells

Antioxidants (Basel). 2021 Feb 13;10(2):284. doi: 10.3390/antiox10020284.

Authors

Melina Mitsiogianni¹, Sotiris Kyriakou^{2

3}, Ioannis Anestopoulos^{2

3}, Dimitrios T Trafalis⁴, Maria V Deligiorgi⁴, Rodrigo Franco^{5

6}, Aglaia Pappa⁷, Mihalis I Panayiotidis^{1

2

3}

Affiliations

¹ Department of Applied Sciences, Northumbria University, Newcastle Upon Tyne NE1 8ST, UK.
² Department of Electron Microscopy & Molecular Pathology, The Cyprus Institute of Neurology & Genetics, Nicosia 2371, Cyprus.
³ The Cyprus School of Molecular Medicine, P.O. Box 23462, Nicosia 1683, Cyprus.
⁴ Laboratory of Pharmacology, Medical School, National & Kapodistrian University of Athens, 11527 Athens, Greece.
⁵ Redox Biology Centre, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
⁶ Department of Veterinary Medicine & Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
⁷ Department of Molecular Biology & Genetics, Democritus University of Thrace, 68100 Alexandroupolis, Greece.

Abstract

Malignant melanoma is one of the most deadly types of solid cancers, a property mainly attributed to its highly aggressive metastatic form. On the other hand, different classes of isothiocyanates, a class of phytochemicals, present in cruciferous vegetables have been characterized by considerable anti-cancer activity in both in vitro and in vivo experimental models. In the current study, we investigated the anti-cancer response of five isothiocyanates in an in vitro model of melanoma consisting of non-metastatic (A375, B16F-10) and metastatic (VMM1, Hs294T) malignant melanoma as well as non-melanoma epidermoid carcinoma (A431) and non-tumorigenic melanocyte-neighboring keratinocyte (HaCaT) cells. Our aim was to compare different endpoints of cytotoxicity (e.g., reactive oxygen species, intracellular glutathione content, cell cycle growth arrest, apoptosis and necrosis) descriptive of an anti-cancer response between non-metastatic and metastatic melanoma as well as non-melanoma epidermoid carcinoma and non-tumorigenic cells. Our results showed that exposure to isothiocyanates induced an increase in intracellular reactive oxygen species and glutathione contents between non-metastatic and metastatic melanoma cells. The distribution of cell cycle phases followed a similar pattern in a manner where non-metastatic and metastatic melanoma cells appeared to be growth arrested at the G2/M phase while elevated levels of metastatic melanoma cells were shown to be at sub G1 phase, an indicator of necrotic cell death. Finally, metastatic melanoma cells were more sensitive apoptosis and/or necrosis as higher levels were observed compared to non-melanoma epidermoid carcinoma and non-tumorigenic cells. In general, non-melanoma epidermoid carcinoma and non-tumorigenic cells were more resistant under any experimental exposure condition. Overall, our study provides further evidence for the potential development of isothiocyanates as promising anti-cancer agents against non-metastatic and metastatic melanoma cells, a property specific for these cells and not shared by non-melanoma epidermoid carcinoma or non-tumorigenic melanocyte cells.

Keywords: allyl isothiocyanate; anti-cancer agents; apoptosis; benzyl isothiocyanate; cell cycle arrest; glutathione; iberin; isothiocyanates; melanoma; necrosis; phenethyl isothiocyanate; reactive oxygen species; sulforaphane.