Journal Article

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

Silvestre, Armando, Santos, Sónia, Duarte, Maria, Guerra, Ângela, Ramos, Patrícia, Freire, Carmen, Oliveira, Helena, Guerreiro, Olinda

2017

Overview

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.

• Publisher: MDPI AG,MDPI
• Subject: Antineoplastic Agents - chemistry / Antineoplastic Agents - pharmacology / Apoptosis - drug effects / CDC2 Protein Kinase / Cell cycle / Cell Line, Tumor / Cell Proliferation - drug effects / Cyclin B1 - genetics / Cyclin B1 - metabolism / Cyclin-Dependent Kinase Inhibitor p21 - genetics / Cyclin-Dependent Kinase Inhibitor p21 - metabolism / Cyclin-Dependent Kinases - genetics / Cyclin-Dependent Kinases - metabolism / Cynara - chemistry / Cynara cardunculus / Humans / Lactones - chemistry / Lactones - pharmacology / Plant Extracts - chemistry / Plant Extracts - pharmacology / Proto-Oncogene Proteins c-akt - genetics / Proto-Oncogene Proteins c-akt - metabolism / Sesquiterpenes - chemistry / Sesquiterpenes - pharmacology