Amaryllidaceae alkaloids in skin cancer management: Photoprotective effect on human keratinocytes and anti-proliferative activity in melanoma cells

J Appl Biomed 21:36-47, 2023 | DOI: 10.32725/jab.2023.004

Carol Castañeda1, Karent Bravo1, Natalie Corts1, 2, Janeth Bedoya3, Warley de S. Borges4, Jaume Bastida5, Edison Osorio1, * 1Universidad de Antioqua, Facultad de Ciencias Farmacuticas y Alimentarias, Grupo de Investigacin en Sustancias Bioactivas, Medelln, Colombia 2Universidad de Ibagu, Facultad de Ciencias Naturales y Matemticas, Ibagu, Colombia 3Universidad de Antioquia, Facultad de Medicina, Grupo Medicina Molecular y de Translacin, Medelln, Colombia 4Universidade Federal do Esprito Santo, Departamento de Qumica, Vitria, Esprito Santo, Brazil 5Universitat de Barcelona, Facultat de Farmàcia i Ciències de l'Alimentaci, Departament de Biologia, Sanitat i Medi Ambient, Barcelona, Spain

Skin cancer has high rates of mortality and therapeutic failure. In this study, to develop a multi-agent strategy for skin cancer management, the selective cytotoxicity of several alkaloid fractions and pure alkaloids isolated from Amaryllidaceae species was evaluated in melanoma cells. In addition, UVB-stimulated keratinocytes (HaCaT) were exposed to seven alkaloid fractions characterized by GC-MS, and the production of intracellular reactive oxygen species (ROS) and IL-6, were measured to evaluate their photoprotection effects. The Eucharis caucana (bulb) alkaloid fraction (20 μg/ml) had a clear effect on the viability of melanoma cells, reducing it by 45.7% without affecting healthy keratinocytes. This alkaloid fraction and tazettine (both at 2.5 μg/ml) suppressed UVB-induced ROS production by 31.6% and 29.4%, respectively. The highest anti-inflammatory potential was shown by the Zephyranthes carinata (bulb) alkaloid fraction (10 μg/ml), which reduced IL-6 production by 90.8%. According to the chemometric analysis, lycoramine and tazettine had a photoprotective effect on the UVB-exposed HaCaT cells, attenuating the production of ROS and IL-6. These results suggest that Amaryllidaceae alkaloids have photoprotective and therapeutic potential in skin cancer management, especially at low concentrations.

Keywords: Amaryllidaceae alkaloids; Eucharis caucana; Photoprotection; Skin cancer; Zephyranthes carinata Grants and funding:

This investigation received financial support from MINCIENCIAS (agreement # 614-2018). The authors would like to express their gratitude to the Iberian-American Programme for Cooperation and Development (CYTED) (Ref. 416RT0511) – BIFRENES Thematic Network and Foundation of Support to Research and Innovation of Esprito Santo (FAPES Universal No. 80708382/18). We would also like to acknowledge INCTBioNat (CNPq 465637/2014-0 and FAPESP 2014/50926-0) for the additional support. The authors are especially grateful to the University of Antioquia (UdeA) for its important contribution in the development of this work. None of these institutions had anything to do with the preparation of the article, the study design, collection, analysis, and interpretation of data, or with the writing of the report and the decision to submit the article for publication.

Conflicts of interest:

The authors have no conflict of interests to declare.

Castañeda C, Bravo K, Corts N, Bedoya J, de Borges WS, Bastida J, Osorio E. Amaryllidaceae alkaloids in skin cancer management: Photoprotective effect on human keratinocytes and anti-proliferative activity in melanoma cells. J Appl Biomed. 2023;21(1):36-47. doi:10.32725/jab.2023.004.

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