Reprogramming of glucose metabolism provides sufficient energy and raw materials for the proliferation, metastasis, and immune escape of cancer cells, which is enabled by glucose metabolism-related enzymes that are abundantly expressed in a broad range of cancers. Therefore, targeting glucose metabolism enzymes has emerged as a promising strategy for anticancer drug development. Although several glucose metabolism modulators have been approved for cancer treatment in recent years, some limitations exist, such as a short half-life, poor solubility, and numerous adverse effects. With the rapid development of medicinal chemicals, more advanced and effective glucose metabolism enzyme-targeted anticancer drugs have been developed. Additionally, several studies have found that some natural products can suppress cancer progression by regulating glucose metabolism enzymes. In this review, we summarize the mechanisms underlying the reprogramming of glucose metabolism and present enzymes that could serve as therapeutic targets. In addition, we systematically review the existing drugs targeting glucose metabolism enzymes, including small-molecule modulators and natural products. Finally, the opportunities and challenges for glucose metabolism enzyme-targeted anticancer drugs are also discussed. In conclusion, combining glucose metabolism modulators with conventional anticancer drugs may be a promising cancer treatment strategy.

The purpose of this study was to characterize the polysaccharides from Athyrium multidentatum (Doll.) Ching (AMC) rhizome and explore the protective mechanism against d-galactose-induced oxidative stress in aging mice. Methods: A series of experiments, including molecular weight, monosaccharide composition, Fourier transform infrared (FT-IR) spectroscopy, and ¹H nuclear magnetic resonance (¹H NMR) spectroscopy were carried out to characterize AMC polysaccharides. The mechanism was investigated exploring d-galactose-induced aging mouse model. Quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) and western blotting assays were performed to assess the gene and protein expression in liver. Key findings: Our results showed that AMC polysaccharides were mainly composed of mannose (Man), rhamnose (Rha), glucuronic acid (Glc A), glucose (Glc), galactose (Gal), arabinose (Ara), and fucose (Fuc) in a molar ratio of 0.077:0.088:0.09:1:0.375:0.354:0.04 with a molecular weight of 33203 Da (Mw). AMC polysaccharides strikingly reversed d-galactose-induced changes in mice, including upregulated phosphatidylinositol 3-kinase (PI3K), Akt, nuclear factor-erythroid 2-related factor 2 (Nrf2), forkhead box O3a (FOXO3a), and hemeoxygenase-1 (HO-1) mRNA expression, raised Bcl-2/Bax ratio, downregulated caspase-3 mRNA expression, enhanced Akt, phosphorylation of Akt (p-Akt), Nrf2 and HO-1 protein expression, decreased caspase-3, and Bax protein expression. Conclusion: AMC polysaccharides attenuated d-galactose-induced oxidative stress and cell apoptosis by activating the PI3K/AKT pathway, which might in part contributed to their anti-aging activity.

Multi‐drug resistance (MDR) is a major cause of cancer therapy failure. Photodynamic therapy (PDT) is a promising modality that can circumvent MDR and synergize with chemotherapies, based on the generation of reactive oxygen species (ROS) by photosensitizers. However, overproduction of glutathione (GSH) by cancer cells scavenges ROS and restricts the efficacy of PDT. Additionally, side effects on normal tissues are unavoidable after PDT treatment. Here, to develop organic systems that deliver effective anticancer PDT and chemotherapy simultaneously with very little side effects, three GSH‐sensitive photosensitizer‐drug conjugates (CyR‐SS‐L) are designed and synthesized. CyR‐SS‐L localized in the mitochondria then is cleaved into CyR‐SG and SG‐L parts by reacting with and consuming high levels of intracellular GSH. Notably, CyR‐SG generates high levels of ROS in tumor cells instead of normal cells and be exploited for PDT and the SG‐L part is used for chemotherapy. CyR‐SS‐L inhibits better MDR cancer tumor inhibitory activity than indocyanine green, a photosensitizer (PS) used for PDT in clinical applications. The results appear to be the first to show that CyR‐SS‐L may be used as an alternative PDT agent to be more effective against MDR cancers without obvious damaging normal cells by the combination of PDT, GSH depletion, and chemotherapy.

The emergence of infections caused by bacterial pathogens that are resistant to current antibiotic therapy is a critical healthcare challenge. Aminoglycosides are natural antibiotics with broad spectrum of activity; however, their clinical use is limited due to considerable nephrotoxicity. Moreover, drug-resistant bacteria that cause infections in human as well as livestock are less responsive to conventional antibiotics. Herein, we report the in vitro antibacterial evaluation of five different aminoglycosides, including ribostamycin, against a panel of Gram-positive and Gram-negative pathogens. Eight of the tested bacterial strains are linked to gastrointestinal (GI) infections. The minimum inhibitory concentration (MIC) of ribostamycin against three different Escherichia coli strains is in the range of 0.9–7.2 μM and against a strain of Haemophilus influenzae is 0.5 μM. We also found that the MIC of ribostamycin was considerably enhanced from 57.2 to 7.2 μM, an 8-fold improvement, when bacteria were treated with a combination of ribostamycin and ethylenediaminetetraacetic acid (EDTA). These findings demonstrate a promising approach to enhance the clinical potential of ribostamycin and provide a rational for its antibiotic reclassification from special level to non-restricted level.

Differentiation therapy with all-trans-retinoic acid (ATRA) in acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia (AML), has been extremely successful in inducing clinical remission in APL patients. However, the differentiation therapy of ATRA-based treatment has not been effective in other subtypes of AML. In this study, we evaluated a small molecule of ent-kaurene diterpenoid, Jiyuan oridonin A (JOA), on the differentiation blockade in AML cells with the mixed lineage leukemia (MLL) gene rearrangements (MLLr) in MV4-11, MOLM-13 and THP-1 cells. We found that JOA could significantly inhibit the proliferation of MOLM-13, MV4-11 and THP-1 cells. Moreover, JOA promoted cell differentiation coupled with cell-cycle exit at G0/G1 and inhibited the colony- forming capacity of these cells. We showed that the anti-proliferative effect of JOA attributed to cell differentiation is most likely through the martens tretinoin response up pathway in the MOLM-13 cell line, and the hematopoietic cell lineage pathway by the inhibition of c-KIT expression and cell adhesion pathway in the THP-1 cell line. Our findings suggest that JOA could be a novel therapeutic agent against human MLLr acute myeloid leukemia.