Reprofiling a classical anthelmintic, pyrvinium pamoate, as an anti-cancer drug targeting mitochondrial respiration

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Reprofiling a classical anthelmintic, pyrvinium pamoate, as an anti-cancer drug targeting mitochondrial respiration

Pyrvinium pamoate (PP) is an FDA-approved classical anthelmintic, but is now attracting particular attention as an anti-cancer drug after recent findings of its potent cytotoxicity against various cancer cell lines only during glucose starvation, as well as its anti-tumor activity against hypovascular pancreatic cancer cells transplanted in mice. The molecular mechanisms by which PP promotes su...

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The Antihelmintic Drug Pyrvinium Pamoate Targets Aggressive Breast Cancer

WNT signaling plays a key role in the self-renewal of tumor initiation cells (TICs). In this study, we used pyrvinium pamoate (PP), an FDA-approved antihelmintic drug that inhibits WNT signaling, to test whether pharmacologic inhibition of WNT signaling can specifically target TICs of aggressive breast cancer cells. SUM-149, an inflammatory breast cancer cell line, and SUM-159, a metaplastic ba...

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An Anthelmintic Drug, Pyrvinium Pamoate, Thwarts Fibrosis and Ameliorates Myocardial Contractile Dysfunction in a Mouse Model of Myocardial Infarction

Metabolic adaptation to limited supplies of oxygen and nutrients plays a pivotal role in health and disease. Heart attack results from insufficient delivery of oxygen and nutrients to the heart, where cardiomyocytes die and cardiac fibroblasts proliferate--the latter causing scar formation, which impedes regeneration and impairs contractility of the heart. We postulated that cardiac fibroblasts...

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Targeting of Wnt/β-Catenin by Anthelmintic Drug Pyrvinium Enhances Sensitivity of Ovarian Cancer Cells to Chemotherapy

BACKGROUND Aberrant activation of Wnt/β-catenin has been shown to promote ovarian cancer proliferation and chemoresistance. Pyrvinium, an FDA-approved anthelmintic drug, has been identified as a potent Wnt inhibitor. Pyrvinium may sensitize ovarian cancer cells to chemotherapy. MATERIAL AND METHODS The effect of pyrvinium alone and its combination with paclitaxel in ovarian cancer was investiga...

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An anticancer agent, pyrvinium pamoate inhibits the NADH-fumarate reductase system--a unique mitochondrial energy metabolism in tumour microenvironments.

Increased glycolysis is the principal explanation for how cancer cells generate energy in the absence of oxygen. However, in actual human tumour microenvironments, hypoxia is often associated with hypoglycemia because of the poor blood supply. Therefore, glycolysis cannot be the sole mechanism for the maintenance of the energy status in cancers. To understand energy metabolism in cancer cells u...

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ژورنال

عنوان ژورنال: Frontiers in Oncology

سال: 2012

ISSN: 2234-943X

DOI: 10.3389/fonc.2012.00137