Dysregulated metabolism is one of the major hallmarks of malignant tumors, which includes increased glycolysis even in the presence of ample oxygen, providing a metabolic advantage for cell proliferation and tumor growth. Recognition of metabolic reprogramming in oncogenesis has paved the way for developing novel therapeutic approaches and agents targeting the key enzymes involved in this process. The therapeutic potential of plant-derived natural bioactive compounds is promising, due to their diverse structures and multiple targets. Angoline, an isoquinoline alkaloid isolated, has been reported to inhibit cancer cell proliferation and tumor growth, but the underlying mechanisms remain largely unclear. Our results showed that Angoline effectively inhibits breast cancer cell proliferation and tumor growth. Mechanistically, angoline directly binds to LDHA and suppresses its activity, resulting in decreased glycolytic rates, less lactate production and increased oxygen consumption in breast cancer cells. Furthermore, the metabolic switch from aerobic glycolysis to oxidative phosphorylation by angoline treatment induces the accumulation of intracellular ROS, which in turn causes a decline in mitochondrial membrane potential and subsequently triggers autophagy. In vivo xenograft model further confirmed the efficacy and safety of angoline in breast cancer treatment. Together, these results suggested that Angoline is a promising natural compound to inhibit LDHA activity, leading to decreased glycolytic rate and increased autophagy related cell death in breast cancer cells. These data together reveal an underlying molecular mechanism of angoline to treat breast cancer.

Acute myeloid leukemia (AML) is a hematopoietic progenitor cell-affected hematological malignancy, caused by the accumulation of genetic and epigenetic abnormalities leading to impaired cell differentiation, enhanced self-renewal capacity, and uncontrolled proliferation. Despite progress in understanding its biology and therapeutic strategies, the mortality rate remains high, with a five-year survival rate below 30%, and the clonal evolution of cells is complex, exhibiting genetic heterogeneity. Glycolysis plays a central role in the metabolic network of cancer cells. Cancer cells produce energy and substances through glycolysis, and their metabolic product, lactic acid, affects the tumor microenvironment (TME), leading to immune suppression, among other effects. Inhibition of glycolysis can enhance the sensitivity of AML to chemotherapeutic drugs. Aging is a risk factor for many diseases and leads to increased incidence and mortality rates of AML. Elderly patients exhibit greater heterogeneity. In AML, the dysfunction of T cells and NK cells is closely related to treatment responses. The process of T cell senescence is complex, involving various phenomena and mechanisms. Senescent T cells have weakened functions, affecting immune surveillance and TME, leading to reduced responses to chemotherapy. This review summarizes the significance of key glycolytic enzymes and aging in AML-related research.