Abstract
Metabolic reprogramming is considered a hallmark of cancer. Currently, the altered lipid metabolism in cancer is a topic of interest due to the prominent role of lipids regulating the progression of various types of tumors. Lipids and lipid-derived molecules have been shown to activate growth regulatory pathways and to promote malignancy in pancreatic cancer. In a previous work, we have described the antitumoral properties of Yarrow (Achillea Millefolium) CO2 supercritical extract (Yarrow SFE) in pancreatic cancer. Herein, we aim to investigate the underlaying molecular mechanisms by which Yarrow SFE induces cytotoxicity in pancreatic cancer cells. Yarrow SFE downregulates SREBF1 and downstream molecular targets of this transcription factor, such as fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD). Importantly, we demonstrate the in vivo effect of Yarrow SFE diminishing the tumor growth in a xenograft mouse model of pancreatic cancer. Our data suggest that Yarrow SFE can be proposed as a complementary adjuvant or nutritional supplement in pancreatic cancer therapy.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Achillea / chemistry*
-
Achillea / metabolism
-
Animals
-
Antineoplastic Agents, Phytogenic / chemistry
-
Antineoplastic Agents, Phytogenic / pharmacology*
-
Antineoplastic Agents, Phytogenic / therapeutic use
-
Cell Line, Tumor
-
Cell Movement / drug effects
-
Down-Regulation / drug effects
-
Fatty Acid Synthases / genetics
-
Fatty Acid Synthases / metabolism
-
Humans
-
Lipid Metabolism / drug effects*
-
Male
-
Mice
-
Mice, Nude
-
Pancreatic Neoplasms / drug therapy
-
Pancreatic Neoplasms / pathology
-
Plant Extracts / chemistry*
-
Plant Extracts / pharmacology
-
Plant Extracts / therapeutic use
-
Protein Isoforms / antagonists & inhibitors
-
Protein Isoforms / genetics
-
Protein Isoforms / metabolism
-
Stearoyl-CoA Desaturase / genetics
-
Stearoyl-CoA Desaturase / metabolism
-
Sterol Regulatory Element Binding Protein 1 / antagonists & inhibitors
-
Sterol Regulatory Element Binding Protein 1 / genetics
-
Sterol Regulatory Element Binding Protein 1 / metabolism
-
Transplantation, Heterologous
Substances
-
Antineoplastic Agents, Phytogenic
-
Plant Extracts
-
Protein Isoforms
-
Sterol Regulatory Element Binding Protein 1
-
Stearoyl-CoA Desaturase
-
Fatty Acid Synthases
Grants and funding
This work was supported by Ministerio de Economía y Competitividad del Gobierno de España (MINECO, Plan Nacional I+D+i AGL2013-48943-C2 and AGL2016-76736-C3), Gobierno regional de la Comunidad de Madrid (P2013/ABI-2728, ALIBIRD-CM) and EU Structural Funds. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.