Abstract
Propolis is rich in flavonoids and has excellent antitumor activity. However, little is known about the potential effects of propolis on glycolysis in tumor cells. Here, the antitumor effects of propolis against human breast cancer MDA-MB-231 cells in an inflammatory microenvironment stimulated with lipopolysaccharide (LPS) were investigated by assessing the key enzymes of glycolysis. Propolis treatment obviously inhibited MDA-MB-231 cell proliferation, migration and invasion, clone forming, and angiogenesis. Proinflammatory mediators, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-6, as well as NLRP3 inflammasomes, were decreased following propolis treatment when compared with the LPS group. Moreover, propolis treatment significantly downregulated the levels of key enzymes of glycolysis–hexokinase 2 (HK2), phosphofructokinase (PFK), pyruvate kinase muscle isozyme M2 (PKM2), and lactate dehydrogenase A (LDHA) in MDA-MB-231 cells stimulated with LPS. After treatment with 2-deoxy-D-glucose (2-DG), an inhibitor of glycolysis, the inhibitory effect of propolis on migration was not significant when compared with the LPS group. In addition, propolis increased reactive oxygen species (ROS) levels and decreased mitochondrial membrane potential. Taken together, these results indicated that propolis targeted key enzymes of glycolysis to suppress the proliferation of MDA-MB-231 cells in an inflammatory microenvironment. These studies provide a molecular basis for propolis as a natural anticancer agent against breast cancer.
Highlights
Breast cancer (BC) is one of the most common malignant tumors and a major cause of cancer death among women worldwide, and the triple-negative breast cancer (TNBC) subtype is the most aggressive one [1]
We reported that Chinese propolis and its major constituent—caffeic acid phenethyl ester (CAPE)—inhibit breast cancer cell proliferation in an inflammatory microenvironment by inhibiting the Toll-like receptor 4 (TLR4) signal pathway and inducing apoptosis and autophagy [12]
Primary antibodies against β-actin, GAPDH, hexokinase 2 (HK2), PFK, pyruvate kinase muscle isozyme M2 (PKM2), lactate dehydrogenase A (LDHA), NLRP3, and secondary antibody were obtained from ABclonal Biotech (USA)
Summary
Breast cancer (BC) is one of the most common malignant tumors and a major cause of cancer death among women worldwide, and the triple-negative breast cancer (TNBC) subtype is the most aggressive one [1]. Worldwide statistics showed that in 2018, approximately two million new cases were detected, with the total BC cases accounting for 11.6% of all cancers. The search for effective anticancer agents is urgent for BC therapy and to improve the quality of life of patients. Rich in flavonoids, is a resinous substance collected by honeybees (Apis mellifera) from various plant sources. It has been used as a folk medicine since ancient times [2]
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