Targeting Therapy for Breast Carcinoma by ATP Synthase Inhibitor Aurovertin B

Abstract

Targeting of tumor tissues is one of the most powerful approaches to accelerate the efficiency of anticancer treatments. The investigation of effective targets, including proteins specifically and abundantly expressed in abnormal regions, has been one of the most important research topics in cancer therapy. In this study, we performed a proteomic analysis on human breast carcinoma tissues to investigate the tumor-specific protein expression in breast carcinoma. Our study showed that ATP synthase was up-regulated in tumor tissues and was present on the plasma membrane of breast cancer cells. Furthermore, we treated the breast cancer cells with ATP synthase inhibitors and examined the inhibitory efficiency. Aurovertin B, an ATP synthase inhibitor, has strong inhibition on the proliferation of several breast cancer cell lines, but little influence on the normal cell line MCF-10A. Aurovertin B inhibits proliferation of breast cancer cells by inducing apoptosis and arresting cell cycle at the G0/G1 phase. This study showed aurovertin B can be used as an antitumorigenic agent and may be exploited in cancer chemotherapy.

Temporal Phosphoproteome Dynamics Induced by an ATP Synthase Inhibitor Citreoviridin*

“…Our study revealed that citreoviridin treatment resulted in significant changes of phosphorylation levels in numerous proteins. Furthermore, we observed that the cell cycle, protein folding, and mRNA processing might be regulated by citreoviridin-stimulated responses, consistent with previous reports (10,18,66). We also identified other processes that have not been reported to be related to citreoviridin treatment, such as cytoskeletonassociated function, development regulation, and ubiquitinproteasomal proteolysis.…”

Ectopic ATP Synthase Blockade Suppresses Lung Adenocarcinoma Growth by Activating the Unfolded Protein Response

“…Thus, ectopic ATP synthase may be an antigen of tumor cells and involved in the immune response to tumor cells. Treating these cancer cells with biological (i.e., antibody or inhibitor of F 1 of ATP synthase, IF1) or chemical synthetic inhibitors of ectopic ATP synthase markedly inhibits cell growth (15,17), thereby highlighting ectopic ATP synthase as a potential and novel therapeutic target for cancer.…”

“…Although ectopic ATP synthase has been found on the extracellular surface of several different cancer cell types (6,(14)(15)(16)…”

ATP5B (ATP synthase, H+ transporting, mitochondrial F1 complex, beta polypeptide)

“…This protein can even play an important role as a target protein in the treatment of cancers. Using ATP synthase inhibitor aurovertin B, in breast cancer cells MCF-7, the effect of ATP5B protein in tumor progression was found to be reduced (Huang et al, 2008).…”