Receptors are macromolecules that transmit information regulating cell proliferation, differentiation, migration and apoptosis, play key roles in oncogenic processes and correlate with the prognoses of cancer patients. Thus, targeting receptors to constrain cancer development and progression has gained widespread interest. Small molecule compounds of natural origin have been widely used as drugs or adjuvant chemotherapeutic agents in cancer therapies due to their activities of selectively killing cancer cells, alleviating drug resistance and mitigating side effects. Meanwhile, many natural compounds, including those targeting receptors, are still under laboratory investigation for their anti-cancer activities and mechanisms. In this review, we classify the receptors by their structures and functions, illustrate the natural compounds targeting these receptors and discuss the mechanisms of their anti-cancer activities. We aim to provide primary knowledge of mechanistic regulation and clinical applications of cancer therapies through targeting deregulated receptors.

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.

This study enhanced germanium (Ge) enrichment in the liquid fermentation of the edible fungus Lyophyllum decastes in order to boost its biological activity, particularly its antioxidant and immunomodulatory properties. Through the use of single-factor and Plackett–Burman designs, the experiments revealed critical parameters affecting Ge enrichment, including Ge oxide concentration, potato powder concentration, and peptone levels. The optimization of the Box–Behnken response surface methodology resulted in a Ge concentration of 3.61 mg/L, significantly enhancing the biomass, protein, polysaccharide, and flavonoid content in the mycelium. In contrast to traditional fermentation, Ge-rich fermentation enhanced the mycelial biomass by 30.97% and elevated the organic Ge content 50.19-fold. An analysis of the antioxidants revealed that the Ge-enriched mycelial water extract exhibited heightened activity, augmenting TNF-α production in RAW264.7 cells by 73.29% at a concentration of 200 μg/g. These findings indicate that the Ge-enriched fermentation of L. decastes holds promise for functional applications in health-supportive products due to its robust antioxidant and immune-enhancing capabilities.