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Salvia lachnostachys Benth has antitumor and chemopreventive effects against solid Ehrlich carcinoma

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Abstract

Salvia lachnostachys is an herbaceous plant with anti-inflammatory, analgesic and cytotoxic properties. This study investigated the antitumor effect of an ethanolic extract of Salvia lachnostachys leaves (EES) in a solid Ehrlich carcinoma model. Ehrlich cells were inoculated subcutaneously in the right pelvic member (2 × 106 cells) in female Swiss mice. The animals were treated with vehicle (10 mL kg−1, p.o.), EES (30 and 100 mg kg−1, p.o.), or methotrexate (2.5 mg kg−1, i.p.) for 21 days (early treatment) or 14 days (late treatment) after tumor inoculation, or 10 days before tumor inoculation and continued for 21 days after tumor inoculation (chemopreventive treatment). The acute toxicity test was performed according OECD guidelines Late treatment with EES had no antitumor effect. Early treatment with 100 mg kg−1 EES prevented tumor development, increased tumor necrosis factor-α (TNF-α) levels and decreased tumor superoxide dismutase (SOD) activity, interleukin-10 (IL-10) levels and Cyclin D1 expression, and tumor cell necrosis was observed. Chemopreventive treatment with EES for 10 and 31 days prevented tumor development in the same manner. EES treatment for 31 days decreased hepatic and tumor SOD activity, tumor IL-10 levels and Cyclin D1 expression, and increased tumor reduced glutathione, N-acetylglucosaminidase, reactive oxygen species, lipid peroxidation, TNF-α levels and Nrf2 expression. No toxicity was observed in the acute toxicity assay. In conclusion, EES had an antitumor effect by inhibiting Cyclin D1 expression and increasing inflammation with early and chemopreventive treatment. Modulation of the antioxidant system also contribute for the antitumor effects of EES.

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Acknowledgements

We thank LCM, TBS, JPA, and RSC for their help with the experiments, ÉPS for plant collection, CRSS from the Brasilia University (UnB) for providing the Ehrlich cells, Prof. Dr. Rosangela L. Dittrich of VH/UFPR for helping with the hematological analysis, and CTAF-UFPR.

Funding

This work was supported by grants from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil (CAPES—Finance Code 001) and Conselho Nacional de Desenvolvimento Científico e Tecnológico—Brasil (CNPq-No. 307977/2015-3).

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Authors and Affiliations

  1. Pharmacology Department, Biological Sciences Sector, Federal University of Parana, PO Box 19031, Curitiba, PR, 81531-980, Brazil

    Claudia Rita Corso, Maria Carolina Stipp, Eliana Rezende Adami & Alexandra Acco

  2. Postgraduate Program in Pharmaceutical Sciences, University Vale of Itajaí, Itajaí, SC, Brazil

    Luisa Mota da Silva, Marihá Mariott & Sergio Faloni de Andrade

  3. Basic Pathology Department, Federal University of Parana, Curitiba, PR, Brazil

    Edneia Amancio de Souza Ramos & Giseli Klassen

  4. Veterinary Hospital, Federal University of Parana, Curitiba, PR, Brazil

    Olair Carlos Beltrame

  5. Medical Pathology Department, Federal University of Parana, Curitiba, PR, Brazil

    José Ederaldo Queiroz-Telles

  6. Chemistry Department, Federal University of Parana, Curitiba, PR, Brazil

    Cristhian Santos de Oliveira & Maria Élida Alves Stefanello

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  1. Claudia Rita Corso
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Contributions

CRC was responsible for experimental design, experiments execution, statistical analysis and writing; MCS and ERA helped in experiments with mice; LMS, MM and SFA conducted cytokine measurements; EASR and GK conducted qPCR experiment; OCB conduct hematological analysis; JEQT helped in histological analysis; CSO and MEAS provided plant extract; and AA was responsible for data analysis and critically revised the article. All the authors approved the final version of the manuscript.

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Correspondence to Alexandra Acco.

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The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants. The experiments performed with mice followed international rules for laboratory animal use and were approved by the Ethics Committee of Animal Experimentation (CEUA/BIO, UFPR; no. 879). Environmental enrichment was used in all cages along experiments to improve the mice welfare.

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Corso, C.R., Stipp, M.C., Adami, E.R. et al. Salvia lachnostachys Benth has antitumor and chemopreventive effects against solid Ehrlich carcinoma. Mol Biol Rep 46, 4827–4841 (2019). https://doi.org/10.1007/s11033-019-04931-3

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