Ana Carolina B da C Rodrigues1, Felipe P de Oliveira1, Rosane B Dias1, Caroline B S Sales2, Clarissa A G Rocha1, Milena B P Soares3, Emmanoel V Costa4, Felipe M A da Silva4, Waldireny C Rocha5, Hector H F Koolen6, Daniel P Bezerra7. 1. Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador, Bahia 40296-710, Brazil. 2. Department of Biomorphology, Institute of Health Sciences, Federal University of Bahia, Salvador (UFBA), Bahia 40110-902, Brazil. 3. Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador, Bahia 40296-710, Brazil; Center of Biotechnology and Cell Therapy, Hospital São Rafael, Salvador, Bahia 41253-190, Brazil. 4. Department of Chemistry, Federal University of Amazonas (UFAM), Manaus, Amazonas 69077-000, Brazil. 5. Health and Biotechnology Institute, Federal University of Amazonas (UFAM), Coari, Amazonas 69460-000, Brazil. 6. Metabolomics and Mass Spectrometry Research Group, Amazonas State University (UEA), Manaus, Amazonas 690065-130, Brazil. 7. Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador, Bahia 40296-710, Brazil. Electronic address: daniel.bezerra@fiocruz.br.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Salacia impressifolia (Miers) A. C. Smith (family Celastraceae) is a traditional medicinal plant found in the Amazon Rainforest known as "miraruíra", "cipó-miraruíra" or "panu" and is traditionally used to treat dengue, flu, inflammation, pain, diabetes, male impotency, renal affections, rheumatism and cancer. AIM OF THE STUDY: The aim of this study was to investigate in vitro and in vivo anti-leukemia activity of the stem bark of S. impressifolia in experimental models. MATERIALS AND METHODS: The in vitro cytotoxic activity of extracts, fractions and quinonemethide triterpenes (22-hydroxytingenone, tingenone and pristimerin) from the stem bark of S. impressifolia in cultured cancer cells was determined. The in vivo antitumor activity of the ethyl acetate extract (EAE) and of its fraction (FEAE.3) from the stem bark of S. impressifolia was assessed in C.B-17 severe combined immunodeficient (SCID) mice engrafted with human promyelocytic leukemia HL-60 cells. RESULTS: The extract EAE, its fraction FEAE.3, and quinonemethide triterpenes exhibited potent cytotoxicity against cancer cell lines, including in vitro anti-leukemia activity against HL-60 and K-562 cells. Moreover, extract EAE and its fraction FEAE.3 inhibited the in vivo development of HL-60 cells engrafted in C.B-17 SCID mice. Tumor mass inhibition rates were measured as 40.4% and 81.5% for the extract EAE (20 mg/kg) and for its fraction FEAE.3 (20 mg/kg), respectively. CONCLUSIONS: Ethyl acetate extract and its fraction from the stem bark of S. impressifolia exhibit in vitro and in vivo anti-leukemia activity that can be attributed to their quinonemethide triterpenes. These data confirm the ethnopharmacological use of this species and may contribute to the development of a novel anticancer herbal medicine.
ETHNOPHARMACOLOGICAL RELEVANCE: Salacia impressifolia (Miers) A. C. Smith (family Celastraceae) is a traditional medicinal plant found in the Amazon Rainforest known as "miraruíra", "cipó-miraruíra" or "panu" and is traditionally used to treat dengue, flu, inflammation, pain, diabetes, male impotency, renal affections, rheumatism and cancer. AIM OF THE STUDY: The aim of this study was to investigate in vitro and in vivo anti-leukemia activity of the stem bark of S. impressifolia in experimental models. MATERIALS AND METHODS: The in vitro cytotoxic activity of extracts, fractions and quinonemethide triterpenes (22-hydroxytingenone, tingenone and pristimerin) from the stem bark of S. impressifolia in cultured cancer cells was determined. The in vivo antitumor activity of the ethyl acetate extract (EAE) and of its fraction (FEAE.3) from the stem bark of S. impressifolia was assessed in C.B-17 severe combined immunodeficient (SCID) mice engrafted with human promyelocytic leukemia HL-60 cells. RESULTS: The extract EAE, its fraction FEAE.3, and quinonemethide triterpenes exhibited potent cytotoxicity against cancer cell lines, including in vitro anti-leukemia activity against HL-60 and K-562 cells. Moreover, extract EAE and its fraction FEAE.3 inhibited the in vivo development of HL-60 cells engrafted in C.B-17 SCIDmice. Tumor mass inhibition rates were measured as 40.4% and 81.5% for the extract EAE (20 mg/kg) and for its fraction FEAE.3 (20 mg/kg), respectively. CONCLUSIONS:Ethyl acetate extract and its fraction from the stem bark of S. impressifolia exhibit in vitro and in vivo anti-leukemia activity that can be attributed to their quinonemethide triterpenes. These data confirm the ethnopharmacological use of this species and may contribute to the development of a novel anticancer herbal medicine.
Authors: Mateus L Nogueira; Emilly J S P de Lima; Asenate A X Adrião; Sheila S Fontes; Valdenizia R Silva; Luciano de S Santos; Milena B P Soares; Rosane B Dias; Clarissa A Gurgel Rocha; Emmanoel V Costa; Felipe M A da Silva; Marcos A Vannier-Santos; Nállarett M D Cardozo; Hector H F Koolen; Daniel P Bezerra Journal: Molecules Date: 2020-06-09 Impact factor: 4.411