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Antiproliferative Effects of Cynara cardunculus L. var. altilis (DC) Lipophilic Extracts
Patrícia A B Ramos1,2, Ângela R Guerra3,4, Olinda Guerreiro5,6
1Centro de Biotecnologia Agrícola e Agro-Alimentar do Alentejo (CEBAL)/Instituto Politécnico de Beja (IPBeja), 7801-908 Beja, Portugal. patricia.ramos@cebal.pt.
Insights
Cardoon leaf extract and cynaropicrin show anticancer effects against triple-negative breast cancer (TNBC) cells. These natural compounds may offer a basis for new TNBC therapies.
Area of Science:
- Phytochemistry
- Oncology
- Molecular Biology
Background:
- *Cynara cardunculus* L. (cardoon) has traditional uses for liver disorders.
- Cardoon exhibits potential anticancer properties, particularly against triple-negative breast cancer (TNBC).
- Lipophilic extracts and specific compounds from cardoon warrant investigation for their efficacy against TNBC cell lines.
Purpose of the Study:
- To evaluate the antiproliferative effects of cardoon leaf and floret extracts and their major compounds (cynaropicrin, taraxasteryl acetate) on MDA-MB-231 TNBC cells.
- To investigate the molecular mechanisms underlying the observed antiproliferative activity, including effects on cell cycle regulation and signaling pathways.
- To determine the potential of cardoon extracts and cynaropicrin as natural therapeutic agents for TNBC.
Main Methods:
- Preparation and testing of lipophilic extracts from *C. cardunculus* L. var. *altilis* leaves and florets.
- Assessment of antiproliferative activity using IC50 values against MDA-MB-231 cells.
- Anchorage-independent growth assay to evaluate colony formation inhibition.
- Spectrophotometric assay for caspase-3 activity and Western blotting for cell cycle and Akt pathway proteins.
Main Results:
- Cardoon leaves extract demonstrated significantly higher antiproliferative activity (IC50 = 10.39 µg/mL) against MDA-MB-231 cells compared to florets extract (IC50 = 315.22 µg/mL).
- Leaves extract and cynaropicrin inhibited colony formation of MDA-MB-231 cells (IC50 = 6.19 µg/mL for cynaropicrin).
- Leaves extract increased caspase-3 activity, while both leaves extract and cynaropicrin induced G2/mitosis cell cycle arrest via p21 upregulation and altered CDK1/cyclin B1 expression, and downregulated phospho-Akt.
Conclusions:
- Lipophilic extracts from cultivated cardoon leaves and the compound cynaropicrin possess significant antiproliferative effects against TNBC cells.
- The observed effects are mediated through mechanisms including G2 cell cycle arrest and Akt signaling pathway modulation.
- Cardoon leaf extract and cynaropicrin represent promising candidates for developing natural-based therapeutic strategies for TNBC.
Abstract:
Besides being traditionally used to relieve hepatobiliary disorders, Cynara cardunculus L. has evidenced anticancer potential on triple-negative breast cancer (TNBC). This study highlights the antiproliferative effects of lipophilic extracts from C. cardunculus L. var. altilis (DC) leaves and florets, and of their major compounds, namely cynaropicrin and taraxasteryl acetate, against MDA-MB-231 cells. Our results demonstrated that MDA-MB-231 cells were much less resistant to leaves extract (IC50 10.39 µg/mL) than to florets extract (IC50 315.22 µg/mL), during 48 h. Moreover, leaves extract and cynaropicrin (IC50 6.19 µg/mL) suppressed MDA-MB-231 cells colonies formation, via an anchorage-independent growth assay. Leaves extract and cynaropicrin were also assessed regarding their regulation on caspase-3 activity, by using a spectrophotometric assay, and expression levels of G2/mitosis checkpoint and Akt signaling pathway proteins, by Western blotting. Leaves extract increased caspase-3 activity, while cynaropicrin did not affect it. Additionally, they caused p21Waf1/Cip1 upregulation, as well as cyclin B1 and phospho(Tyr15)-CDK1 accumulation, which may be related to G2 cell cycle arrest. They also downregulated phospho(Ser473)-Akt, without changing total Akt1 level. Cynaropicrin probably contributed to leaves extract antiproliferative action. These promising insights suggest that cultivated cardoon leaves lipophilic extract and cynaropicrin may be considered toward a natural-based therapeutic approach on TNBC.
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