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Chlorogenic Acid: The Conceivable Chemosensitizer Leading to Cancer Growth Suppression.

ABSTRACT: New paradigm in cancer pathogenesis revealed that microenvironmental conditions significantly contribute to cancer. Hence, Warburg stated that cancer is a metabolic disease. Chlorogenic acid (CGA) is a polyphenol that is found abundantly in coffee. This compound has proven ability in ameliorating some metabolic diseases through various pathways. This article will elaborate the potency of CGA as a chemosensitizer in suppressing tumor growth through a metabolic pathway. AMPK pathway is the main cell metabolic pathway that is activated by CGA in some studies. Moreover, CGA inhibited EGFR/PI3K/mTOR, HIF, VEGF pathways and MAPK/ERK pathway that may suppress tumor cell growth. Furthermore, CGA induced intracellular DNA damage and topoisomerase I- and II-DNA complexes formation that plays a key role in apoptosis. Conclusively, based on the ability of CGA in activate and inhibit some important pathways in cancer metabolism, it may act as a chemosensitizing agent leading to cancer growth suppression.

SUBMITTER: Lukitasari M

PROVIDER: S-EPMC6073821 | biostudies-literature | 2018 Jan-Dec

REPOSITORIES: biostudies-literature

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Chlorogenic Acid: The Conceivable Chemosensitizer Leading to Cancer Growth Suppression.

Lukitasari Mifetika M Nugroho Dwi Adi DA Widodo Nashi N

Journal of evidence-based integrative medicine 20180101

New paradigm in cancer pathogenesis revealed that microenvironmental conditions significantly contribute to cancer. Hence, Warburg stated that cancer is a metabolic disease. Chlorogenic acid (CGA) is a polyphenol that is found abundantly in coffee. This compound has proven ability in ameliorating some metabolic diseases through various pathways. This article will elaborate the potency of CGA as a chemosensitizer in suppressing tumor growth through a metabolic pathway. AMPK pathway is the main ce ...[more]

PMID: 30051721

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Project description:RATIONALE:Inducing cancer differentiation is a promising approach to treat cancer. Here, we identified chlorogenic acid (CA), a potential differentiation inducer, for cancer therapy, and elucidated the molecular mechanisms underlying its differentiation-inducing effects on cancer cells. METHODS:Cancer cell differentiation was investigated by measuring malignant behavior, including growth rate, invasion/migration, morphological change, maturation, and ATP production. Gene expression was analyzed by microarray analysis, qRT-PCR, and protein measurement, and molecular biology techniques were employed for mechanistic studies. LC/MS analysis was the method of choice for chemical detection. Finally, the anticancer effect of CA was evaluated both in vitro and in vivo. Results: Cancer cells treated with CA showed reduced proliferation rate, migration/invasion ability, and mitochondrial ATP production. Treating cancer cells with CA resulted in elevated SUMO1 expression through acting on its 3'UTR and stabilizing the mRNA. The increased SUMO1 caused c-Myc sumoylation, miR-17 family downregulation, and p21 upregulation leading to G0/G1 arrest and maturation phenotype. CA altered the expression of differentiation-related genes in cancer cells but not in normal cells. It inhibited hepatoma and lung cancer growth in tumor-bearing mice and prevented new tumor development in naïve mice. In glioma cells, CA increased expression of specific differentiation biomarkers Tuj1 and GFAP inducing differentiation and reducing sphere formation. The therapeutic efficacy of CA in glioma cells was comparable to that of temozolomide. CA was detectable both in the blood and brain when administered intraperitoneally in animals. Most importantly, CA was safe even at very high doses. CONCLUSION:CA might be a safe and effective differentiation-inducer for cancer therapy. "Educating" cancer cells to differentiate, rather than killing them, could be a novel therapeutic strategy for cancer.

Project description:Fibrosis and cancer is described by some epidemiological studies as chronic stages of different disease conditions typically characterized by uncontrolled accumulation of extra-cellular matrix (ECM), thereby leading to inflammation of tissues and organ (lungs, heart, liver and kidney) dysfunction. It is highly prevalent, and contributes to increased mortality rate worldwide. Currently, the therapeutical approaches involving selected medications (bemcentinib, pirfenidone and nintedanib) obtained synthetically, and used in clinical practices for fibrosis and cancer management and treatment has shown to be unsatisfactorily, especially during progressive stages of the disease. With regards to finding a more potent, effective, and promising curative for fibrosis and cancer, there is need for continuous experimental studies universally. However, phytochemical constituents' particularly phenolic compounds [Chlorogenic acid (CGA)] obtained from coffee, and coffee beans have been predominantly utilized in experimental studies, due to its multiple pharmacological properties against various disease forms. Considering its natural source alongside minimal toxicity level, CGA, a major precursor of coffee have gained considerable attention nowadays from researchers worldwide, owing to its wide, efficacious and beneficial action against fibrosis and cancer. Interestingly, the safety of CGA has been proven. Furthermore, numerous experimental studies have also deduced massive remarkable outcomes in the use of CGA clinically, as a potential drug candidate against treatment of fibrosis and cancer. In the course of this review article, we systematically discussed the beneficial contributions of CGA with regards to its source, absorption, metabolism, mechanistic effects, and molecular mechanisms against different fibrosis and cancer categorization, which might be a prospective remedy in the future. Moreover, we also highlighted CGA (in vitro and in vivo analytical studies) defensive effects against various disorders.

Dataset Information

Chlorogenic Acid: The Conceivable Chemosensitizer Leading to Cancer Growth Suppression.

Publications

Chlorogenic Acid: The Conceivable Chemosensitizer Leading to Cancer Growth Suppression.

Similar Datasets

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