Lycopene-rich extract from red guava (Psidium guajava L.) displays cytotoxic effect against human breast adenocarcinoma cell line MCF-7 via an apoptotic-like pathway

Raimunda C Dos Santos; Alicia S Ombredane; Jéssica Maria T Souza; Andreanne G Vasconcelos; Alexandra Plácido; Adriany das G N Amorim; Eder Alves Barbosa; Filipe C D A Lima; Cristina D Ropke; Michel M M Alves; Daniel D R Arcanjo; Fernando A A Carvalho; Cristina Delerue-Matos; Graziella A Joanitti; José Roberto de S A Leite

doi:10.1016/j.foodres.2017.10.045

Lycopene-rich extract from red guava (Psidium guajava L.) displays cytotoxic effect against human breast adenocarcinoma cell line MCF-7 via an apoptotic-like pathway

Food Res Int. 2018 Mar:105:184-196. doi: 10.1016/j.foodres.2017.10.045. Epub 2017 Oct 27.

Authors

Raimunda C Dos Santos¹, Alicia S Ombredane², Jéssica Maria T Souza¹, Andreanne G Vasconcelos¹, Alexandra Plácido³, Adriany das G N Amorim¹, Eder Alves Barbosa⁴, Filipe C D A Lima⁵, Cristina D Ropke⁶, Michel M M Alves⁷, Daniel D R Arcanjo⁷, Fernando A A Carvalho⁷, Cristina Delerue-Matos³, Graziella A Joanitti⁸, José Roberto de S A Leite⁹

Affiliations

¹ Núcleo de Pesquisa em Biodiversidade e Biotecnologia, Biotec, Campus Ministro Reis Velloso, Universidade Federal do Piauí, Parnaíba, PI, Brazil.
² Laboratório de Nanobiotecnologia, Instituto de Biologia, Campus Darcy Ribeiro, Universidade de Brasília, Brasília, DF, Brazil.
³ REQUIMTE/LAQV, Instituto Superior de Engenharia do Porto, Instituto Politécnico do Porto, Porto, Portugal.
⁴ Laboratório de Síntese e Análise de Biomoléculas, LSAB, Instituto de Química, Campus Darcy Ribeiro, Universidade de Brasília, Brasília, DF, Brazil; Laboratório de Espectrometria de Massa, Embrapa Recursos Genéticos e Biotecnologia, Brasília, DF, Brazil.
⁵ Instituto Federal de Educação Ciência e Tecnologia de São Paulo, Matão, SP, Brazil.
⁶ Phytobios LTDA, Barueri, SP, São Paulo, Brazil.
⁷ Núcleo de Pesquisa em Plantas Medicinais, Universidade Federal do Piauí, Teresina, PI, Brazil.
⁸ Laboratório de Nanobiotecnologia, Instituto de Biologia, Campus Darcy Ribeiro, Universidade de Brasília, Brasília, DF, Brazil; Campus Ceilândia, Centro Metropolitano, Universidade de Brasília, Ceilândia, Brasília, DF, Brazil.
⁹ Área de Morfologia, Faculdade de Medicina, Campus Darcy Ribeiro, Universidade de Brasília, Brasília, DF, Brazil. Electronic address: jrsaleite@pq.cnpq.br.

PMID: 29433206
DOI: 10.1016/j.foodres.2017.10.045

Abstract

This study investigated a lycopene-rich extract from red guava (LEG) for its chemical composition using spectrophotometry, mass spectrometry, attenuated total reflectance-fourier transform infrared spectroscopy (ATR-FTIR), and computational studies. The cytotoxic activity of LEG and the underlying mechanism was studied in human breast adenocarcinoma cells (MCF-7), murine fibroblast cells (NIH-3T3), BALB/c murine peritoneal macrophages, and sheep blood erythrocytes by evaluating the cell viability with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and flow cytometry. Spectrophotometry analysis showed that LEG contained 20% of lycopene per extract dry weight. Experimental and theoretical ATR-FTIR suggests the presence of lycopene, whereas MS/MS spectra obtained after fragmentation of the molecular ion [M]^+• of 536.4364 show fragment ions at m/z 269.2259, 375.3034, 444.3788, and 467.3658, corroborating the presence of lycopene mostly related to all-trans configuration. Treatment with LEG (1600 to 6.25μg/mL) for 24 and 72h significantly affected the viability of MCF-7 cells (mean half maximal inhibitory concentration [IC₅₀]=29.85 and 5.964μg/mL, respectively) but not NIH-3T3 cells (IC₅₀=1579 and 911.5μg/mL, respectively). Furthermore LEG at concentrations from 800 to 6.25μg/mL presented low cytotoxicity against BALB/c peritoneal macrophages (IC₅₀≥800μg/mL) and no hemolytic activity. LEG (400 and 800μg/mL) caused reduction in the cell proliferation and induced cell cycle arrest, DNA fragmentation, modifications in the mitochondrial membrane potential, and morphologic changes related to granularity and size in MCF-7 cells; however, it failed to cause any significant damage to the cell membrane or display necrosis or traditional apoptosis. In conclusion, LEG was able to induce cytostatic and cytotoxic effects on breast cancer cells probably via induction of an apoptotic-like pathway.

Keywords: Antioxidant; Breast cancer; Carotenoid; Cytotoxicity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / drug effects*
Cell Cycle / drug effects
Cell Membrane
Cell Proliferation / drug effects
Cell Survival / drug effects
DNA Fragmentation / drug effects
Female
Humans
Lycopene / analysis*
Lycopene / pharmacology*
MCF-7 Cells
Male
Mice
Mice, Inbred BALB C
NIH 3T3 Cells
Plant Extracts / analysis*
Plant Extracts / pharmacology*
Psidium / chemistry*
Reactive Oxygen Species / metabolism
Tandem Mass Spectrometry

Substances

Plant Extracts
Reactive Oxygen Species
Lycopene