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Yarrow supercritical extract exerts antitumoral properties by targeting lipid metabolism in pancreatic cancer.

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.

SUBMITTER: Mouhid L

PROVIDER: S-EPMC6435158 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Yarrow supercritical extract exerts antitumoral properties by targeting lipid metabolism in pancreatic cancer.

Mouhid Lamia L Gómez de Cedrón Marta M García-Carrascosa Elena E Reglero Guillermo G Fornari Tiziana T Ramírez de Molina Ana A

PloS one 20190326 3

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) i ...[more]

PMID: 30913248

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Project description:Lung cancer is one of the most deadly and common cancers in the world. The molecular features of patient's tumours dictate the different therapeutic decisions, which combines targeted therapy, chemotherapy, and immunotherapy. Altered cellular metabolism is one of the hallmarks of cancer. Tumour cells reprogram their metabolism to adapt to their novel requirements of growth, proliferation, and survival. Together with the Warburg effect, the role of lipid metabolism alterations in cancer development and prognosis has been highlighted. Several lipid related genes have been shown to promote transformation and progression of cancer cells and have been proposed as biomarkers for prognosis. Nevertheless, the exact mechanisms of the regulation of lipid metabolism and the biological consequences in non-small cell lung cancer (NSCLC) have not been elucidated yet. There is an urgent necessity to develop multidisciplinary and complementary strategies to improve NSCLC patients´ well-being and treatment response. Nutrients can directly affect fundamental cellular processes and some diet-derived ingredients, bioactive natural compounds and natural extracts have been shown to inhibit the tumour growth in preclinical and clinical trials. Previously, we described a supercritical extract of rosemary (SFRE) (12 - 16% composition of phenolic diterpenes carnosic acid and carnosol) as a potential antitumoral agent in colon and breast cancer due to its effects on the inhibition of lipid metabolism and DNA synthesis, and in the reduction of resistance to 5-FluoroUracil (5-FU). Herein, we demonstrate SFRE inhibits NSCLC cell bioenergetics identifying several lipid metabolism implicated targets. Moreover, SFRE synergises with standard therapeutic drugs used in the clinic, such as cisplatin, pemetrexed and pembrolizumab to inhibit of cell viability of NSCLC cells. Importantly, the clinical relevance of SFRE as a complement in the treatment of NSCLC patients is suggested based on the results of a pilot clinical trial where SFRE formulated with bioactive lipids (PCT/ES2017/070263) diminishes metabolic and inflammatory targets in peripheral-blood mononuclear cells (PBMC), such as MAPK (p=0.04), NLRP3 (p=0.044), and SREBF1 (p=0.047), which may augment the immune antitumour function. Based on these results, SFRE merits further investigation as a co-adjuvant in the treatment of NSCLC.Clinical trial registrationClinicalTrials.gov Identifier NCT05080920.

Dataset Information

Yarrow supercritical extract exerts antitumoral properties by targeting lipid metabolism in pancreatic cancer.

Publications

Yarrow supercritical extract exerts antitumoral properties by targeting lipid metabolism in pancreatic cancer.

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