Novel Docosahexaenoic Acid Ester of Phloridzin Inhibits Proliferation and Triggers Apoptosis in an In Vitro Model of Skin Cancer

Theodora Mantso; Dimitrios T Trafalis; Sotiris Botaitis; Rodrigo Franco; Aglaia Pappa; H P Vasantha Rupasinghe; Mihalis I Panayiotidis

doi:10.3390/antiox7120188

Novel Docosahexaenoic Acid Ester of Phloridzin Inhibits Proliferation and Triggers Apoptosis in an In Vitro Model of Skin Cancer

Antioxidants (Basel). 2018 Dec 11;7(12):188. doi: 10.3390/antiox7120188.

Authors

Theodora Mantso¹, Dimitrios T Trafalis², Sotiris Botaitis³, Rodrigo Franco^{4

5}, Aglaia Pappa⁶, H P Vasantha Rupasinghe^{7

8}, Mihalis I Panayiotidis⁹

Affiliations

¹ Department of Applied Sciences, Northumbria University, Newcastle Upon Tyne NE1 8ST, UK. theodora.mantso@northumbria.ac.uk.
² Laboratory of Pharmacology, Unit of Clinical Pharmacology, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece. dtrafal@med.uoa.gr.
³ Second Department of Surgery, Democritus University of Thrace, Alexandroupolis 68100, Greece. smpotait@med.duth.gr.
⁴ Redox Biology Centre, University of Nebraska, Lincoln, NE 68588, USA. rodrigo.franco@unl.edu.
⁵ Department of Veterinary & Biomedical Sciences, University of Nebraska, Lincoln, NE 68583, USA. rodrigo.franco@unl.edu.
⁶ Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis 68100, Greece. apappa@mbg.duth.gr.
⁷ Department of Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Halifax, NS B2N 5E3, Canada. vrupasinghe@dal.ca.
⁸ Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 4R2, Canada. vrupasinghe@dal.ca.
⁹ Department of Applied Sciences, Northumbria University, Newcastle Upon Tyne NE1 8ST, UK. m.panagiotidis@northumbria.ac.uk.

Abstract

Skin cancer is among the most common cancer types accompanied by rapidly increasing incidence rates, thus making the development of more efficient therapeutic approaches a necessity. Recent studies have revealed the potential role of decosahexaenoic acid ester of phloridzin (PZDHA) in suppressing proliferation of liver, breast, and blood cancer cell lines. In the present study, we investigated the cytotoxic potential of PZDHA in an in vitro model of skin cancer consisting of melanoma (A375), epidermoid carcinoma (A431), and non-tumorigenic (HaCaT) cell lines. Decosahexaenoic acid ester of phloridzin led to increased cytotoxicity in all cell lines as revealed by cell viability assays. However, growth inhibition and induction of both apoptosis and necrosis was more evident in melanoma (A375) and epidermoid carcinoma (A431) cells, whereas non-tumorigenic keratinocytes (HaCaT) appeared to be more resistant as detected by flow cytometry. More specifically, PZDHA-induced cell cycle growth arrest at the G2/M phase in A375 and A431 cells in contrast to HaCaT cells, which were growth arrested at the G0/G1 phase. Elevated intracellular generation of reactive oxygen species ROS was detected in all cell lines. Overall, our findings support the potential of PZDHA as a novel therapeutic means against human skin cancer.

Keywords: apoptosis; cell cycle; docosahexaenoic acid; epidermoid carcinoma; flavonoids; melanoma; necrosis; oxidative stress; phloridzin; reactive oxygen species; skin cancer.