CYTOTOXIC AND PHYTOCHEMICAL PROFILES

CYTOTOXIC AND PHYTOCHEMICAL PROFILES OF Melipona scutellaris
GEOPROPOLIS AND ITS ACTIVE HEXANE FRACTION
1
Rosalen, P.L.; 1Cunha, M.G.; 1Franchin, M.; 1Galvão, L.C.C.; 2Ruiz, A.L.T.G.;
Carvalho, J.E.; 3Ikegaki, M., 4Alencar, S.M.
2
1 Department of Physiological Sciences, Piracicaba Dental School, University of
Campinas - UNICAMP, Av. Limeira 901, 13414-903, Piracicaba, SP, Brazil;
2 Research Center for Chemistry, Biology, and Agriculture, University of
Campinas - UNICAMP, CP 6171, 13083-970, Campinas, SP, Brazil;
3 College of Pharmaceutical Sciences, Federal University of Alfenas, 37130–
000, Alfenas, MG, Brazil;
4 Department of Agri-Food Industry, Food, and Nutrition, “Luiz de Queiroz”
College of Agriculture, University of São Paulo, Av. Pádua Dias, 11, Piracicaba,
SP, Brazil.
Aim: The aim was to assess the cytotoxic profile of ethanol extract of
geopropolis (EEGP) and its hexane fraction (HF) as well as their phytochemical
characteristics.
Methods: Crude samples of M. scutellaris geopropolis were obtained in the
coastal region of the city of Entre Rios, Bahia (11°57' S, 38°05' W), Brazil, on
June, 2011. EEGP was prepared using absolute ethanol (1:7; w/v) and then
fractioned by liquid-liquid partition in order to obtain fractions with different
polarity degrees. The cytotoxic activity of EEGP and HF (0.25, 2.5, 25 and 250
µg/mL) was evaluated against normal cell lines [mouse fibroblasts (3T3) and
human keratinocyte (HaCat)] and human tumor cell lines [glioma (U251),
melanoma (UACC-62), breast (MCF-7), multidrug resistant ovarian cancer (NCI
/ ADR-RES), kidney (786-0), lung (NCI/H460), prostate (PC-3 ) and ovarian
(OVCAR-3)]. Doxorubicin (0.025, 0.25, 2.5 and 25 µg/mL) was used as positive
control. After 48 hours of exposure, cell growth was assessed by quantification
of the protein content by the sulforhodamine B method. Through the obtained
cell growth curve it was calculated the required concentration to completely cell
growth inhibition (TGI). The chemical characterization of HF and EEGP was
performed by high performance liquid chromatography on reverse phase (RPHPLC) and gas chromatography-mass spectrometry GC-MS.
Results: EEGP showed to be inactive against the normal strains tested (TGI>
50 µg/mL) and completely inhibited the tumor cell lines growth at lower
concentrations when compared to normal strains. HF showed moderate activity
against normal strains (6.25 µg/mL <TGI <15 µg/mL) and strong inhibitory
activity (TGI <6.25 µg/mL) on most of tumor cell lines tested, especially against
ovary (OVCAR-3) and melanoma (UACC-62). Benzophenones were identified
as major compounds in EEGP and HF and no pattern of phenolic acids and
flavonoids commonly found in Apis mellifera propolis were identified.
Conclusion: Geopropolis showed interesting cytotoxic profile, with low toxicity
against normal strains and selectivity against some tumor cell lines, suggesting
a low toxicity of this natural product. Also, due to the presence of
benzophenones, geopropolis presents a chemical profile distinguished from
other types of propolis.
Financial support: FAPESP # 2010/20214-7 e # 2011/23635-6.