Antiproliferative Effects of Cynara cardunculus L. var. altilis (DC) Lipophilic Extracts

Abstract

Besides being traditionally used to relieve hepatobiliary disorders, <i>Cynara cardunculus</i> L. has evidenced anticancer potential on triple-negative breast cancer (TNBC). This study highlights the antiproliferative effects of lipophilic extracts from <i>C. cardunculus</i> L. var. <i>altilis</i> (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 p21^Waf1/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.