V181A and R68G as putative markers of cynaropicrin content related to antiproliferative activity of breast cancer cells

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V181A and R68G as putative markers of cynaropicrin content related to antiproliferative activity of breast cancer cells

Tuesday, 13.03.2018

Researchers at the Centre of Agronomic and Agro-Industrial Biotechnology of Alentejo (CEBAL) in Beja identified, in a natural population of Cynara cardunculus, two allelic variants in GAS (Germacrene A Synthase) gene sequence with significant associations between the cynaropicrin content (a lactone sesquiterpene) and the antiproliferative activity of a breast cancer cell line (MDA-MD-231), in vitro. Cynara cardunculus is known to be a natural source of terpenic compounds, being one of the predominant molecules cynaropicrin, which has been implicated in a wide variety of biological processes. In this work, researchers also showed that Cynara cardunculus leaf lipophilic‐derived extracts are not only rich in cynaropicrin, taraxasterol and taraxasteryl acetate, but also present antithrombotic, antimicrobial and antiproliferative properties.

This study of the natural genetic variability in C. cardunculus, recently published in Molecular Genetics and Genomics journal, may be useful for the development of plant breeding programs with increased bioactive compounds, and greater nutritional and/or pharmaceutical quality of specific ecotypes.


Authors and Affiliations

Ana Margarida Ferro1,2; Patrícia Ramos1,3; Ângela Guerra1,3; Paula Parreira1; Teresa Brás1,4; Olinda Guerreiro1,5; Eliana Jerónimo1; Carmen Capel6; Juan Capel6; Fernando J. Yuste-Lisbona6; Maria F. Duarte1; Rafael Lozano6; M. Margarida Oliveira2; Sónia Gonçalves1,*

1Centro de Biotecnologia Agrícola e Agro-Alimentar do Alentejo (CEBAL)/ Instituto Politécnico de Beja (IPBeja), Rua Pedro Soares, 7801-908 Beja, Portugal;

2Instituto de Tecnologia Química e Biológica António Xavier (ITQB), Universidade Nova de Lisboa, Av. da República, 2781-901 Oeiras, Portugal;

3CICECO/ Departamento de Química, Universidade de Aveiro, 3810-193 Aveiro, Portugal;

4LAQV/ REQUIMTE, FCT, Universidade Nova de Lisboa, Campus de Caparica, 2829-516 Caparica, Portugal

5Centro de Investigação Interdisciplinar em Sanidade Animal (CIISA), Faculdade de Medicina Veterinária, ULisboa; Avenida da Universidade Técnica 1300-477 Lisboa, Portugal;

6Centro de Investigación en Biotecnología Agroalimentaria (BITAL), Universidad de Almería, 04120 Almeria, Spain.

*Present address: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB101SA Cambridge, United Kingdom.



Cynara cardunculus L. represents a natural source of terpenic compounds, with the predominant molecule being cynaropicrin. Cynaropicrin is gaining interest since it has been correlated to anti-hyperlipidaemia, antispasmodic and cytotoxicity activity against leukocyte cancer cells. The objective of this work was to screen a collection of C. cardunculus, from different origins, for new allelic variants in germacrene A synthase (GAS) gene involved in the cynaropicrin biosynthesis and correlate them with improved cynaropicrin content and biological activities. Using high-resolution melting, nine haplotypes were identified. The putative impact of the identified allelic variants in GAS protein was evaluated by bioinformatic tools and polymorphisms that putatively lead to protein conformational changes were described. Additionally, cynaropicrin and main pentacyclic triterpenes contents, and antithrombin, antimicrobial and antiproliferative activities were also determined in C. cardunculus leaf lipophilic-derived extracts. In this work we identified allelic variants with putative impact on GAS protein, which are significantly associated with cynaropicrin content and antiproliferative activity. The results obtained suggest that the identified polymorphisms should be explored as putative genetic markers correlated with biological properties in Cynara cardunculus.



Molecular Genetics and Genomics