Phenolic compounds from Viscum album tinctures enhanced antitumor activity in melanoma murine cancer cells

Michelle Nonato de Oliveira Melo; Adriana Passos Oliveira; Adalgisa Felippe Wiecikowski; Renato Sampaio Carvalho; Juliana de Lima Castro; Felipe Alves Gomes de Oliveira; Henrique Marcelo Gualberto Pereira; Venicio Feo da Veiga; Marcia Marques Alves Capella; Leandro Rocha; Carla Holandino

doi:10.1016/j.jsps.2018.01.011

Phenolic compounds from Viscum album tinctures enhanced antitumor activity in melanoma murine cancer cells

Saudi Pharm J. 2018 Mar;26(3):311-322. doi: 10.1016/j.jsps.2018.01.011. Epub 2018 Jan 31.

Affiliations

¹ Multidisciplinary Laboratory of Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
² Vegetal Biotechnology Program, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
³ Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
⁴ Brazilian Doping Control Laboratory, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
⁵ Microscopy Sector Professor Paulo de Góes, Microbiology Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
⁶ Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
⁷ Department of Pharmaceutical Technology, Faculty of Pharmacy, Fluminense Federal University, Niterói, RJ, Brazil.

Abstract

Cancer is one of the biggest problems in public health worldwide. Plants have been shown important role in anticancer research. Viscum album L. (Santalaceae), commonly known as mistletoe, is a semi-parasitic plant that grows on different host trees. In complementary medicine, extracts from European mistletoe (Viscum album L.) have been used in the treatment of cancer. The study was conducted to identify chemical composition and antitumor potential of Viscum album tinctures. Chemical analysis performed by high resolution chromatography equipped with high resolution mass spectrometer identified caffeic acid, chlorogenic acid, sakuranetin, isosakuranetin, syringenin 4-O-glucoside, syringenin 4-O-apiosyl-glucoside, alangilignoside C and ligalbumoside A compounds. Some of these compounds are probably responsible for the reduction of tumoral cellular growth in a dose-dependent manner. It was observed that melanoma murine cells (B16F10) were more sensitive to V. album tinctures than human leukaemic cells (K562), besides non-tumoral cells (MA-104) had a much lower cytotoxicity to them. Apoptotic-like cells were observed under light microscopy and were confirmed by a typical DNA fragmentation pattern. Additionally, flow cytometry results using Annexin-V/FITC permitted to quantify increased expression of early and late apoptotic markers on tumoral cells, confirming augmented Sub G0 population, which was probably associated with a consistent decrease in G1, and an increase in S or G2/M populations. Results indicate the chemical composition of V. album tinctures influences the mechanisms of in vitro tumoral cell death, suggesting a potential use in cancer pharmacotherapy research.

Keywords: % v/v, % volume/volume; Antitumoral; DMEM, Dulbecco’s Modified Eagle Medium; HPLC, high performance liquid chromatography; HRMS, high resolution mass; Lignans; Mistletoe; NP/PEG, Diphenylboriloxyethilamine/polyetileneglicol; PDA, photodiode array detector; Phenolic compounds; TA, tincture A; TB, tincture B; TLC, Thin Layer Chromatography; UFLC, ultra fast liquid chromatography; UHPLC, ultra high performance liquid chromatography; Viscum album.