Abstract
Aberrant metabolism is one of the hallmarks of cancers. The contributions of dysregulated metabolism to cancer development, such as tumor cell survival, metastasis and drug resistance, have been extensively characterized. “Reprogrammed” metabolic pathways in cancer cells are mainly represented by excessive glucose consumption and hyperactive de novo lipogenesis. Natural compounds with anticancer activities are constantly being demonstrated to target metabolic processes, such as glucose transport, aerobic glycolysis, fatty acid synthesis and desaturation. However, their molecular targets and underlying anticancer mechanisms remain largely unclear or controversial. Mounting evidence indicated that these natural compounds could modulate the expression of key regulatory enzymes in various metabolic pathways at transcriptional and translational levels. Meanwhile, natural compounds could also inhibit the activities of these enzymes by acting as substrate analogs or altering their protein conformations. The actions of natural compounds in the crosstalk between metabolism modulation and cancer cell destiny have become increasingly attractive. In this review, we summarize the activities of natural small molecules in inhibiting key enzymes of metabolic pathways. We illustrate the structural characteristics of these compounds at the molecular level as either inhibitor of various enzymes or regulators of metabolic pathways in cancer cells. Our ultimate goal is to both facilitate the clinical application of natural compounds in cancer therapies and promote the development of novel anticancer therapeutics.
Highlights
Rapid proliferation is a key characteristic of cancer cells, which confers them with oncogene addiction and non-oncogene dependence, including metabolic dependence
Menendez et al reported that polyphenols, flavonoids and secoiridoids extracted from olive oil could significantly suppress Fatty acid synthase (FASN) protein levels in HER2-overexpressing breast cancer cells, including HER2 gene-amplified SKBR3 cells and engineered HER2-overexpressing MCF-7 cells
As a key enzyme regulating the final step of glycolysis, pyruvate kinase M2 (PKM2) can stay in two different oligomer statuses in the cytoplasm
Summary
Rapid proliferation is a key characteristic of cancer cells, which confers them with oncogene addiction and non-oncogene dependence, including metabolic dependence. This allows us to design effective strategies and develop new clinical anticancer agents [10]. Various compounds from edible plants and traditional Chinese herbals have been revealed to have suppressive effects on the initiation, development and metastasis of human cancers [11,12]. Some of these compounds with well-characterized anticancer activities, such as paclitaxel, are already in the clinic. The knowledge of the mechanistic action of natural compounds will provide insights in designing combinatorial medication among these molecules or with other anticancer drugs to improve the effectiveness of cancer therapies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
