Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gentian violet (GV) is a cationic triphenylmethane dye, with potent antifungal and antibacterial activity. We recently reported that in vitro GV suppresses the differentiation of bone resorbing osteoclasts while stimulating the differentiation and activity of bone forming osteoblasts. Breast cancer is highly metastatic to bone and drives bone turnover that further promotes cancer engraftment and expansion, the so-called vicious cycle. In humans, breast cancer metastases cause osteolytic lesions and skeletal damage that leads to bone fractures, an additional source of patient morbidity. The MDA-MB-231 human breast cancer cell line is a commonly used model of human breast cancer that when injected into mice metastasizes to bone causing osteolytic lesions by promoting osteoclastic bone resorption and/or suppressing osteoblastic bone formation. In the present study, we investigated the direct action of GV on MDA-MB-231 proliferation, and the capacity of GV to reverse the negative impact of MDA-MB-231 cells on osteoclast and osteoblast differentiation. Our data reveal for the first time that GV suppresses proliferation, and induces apoptosis, of MDA-MB-231 cells. We further demonstrated the capacity of GV to reverse the pro-osteoclastogenic and anti-osteoblastic activities of MDA-MB-231 cells in vitro. These data suggest that GV has important applications in the treatment of breast cancer through multiple actions including direct suppression of cancer cell proliferation, breaking the vicious cycle between cancer and bone, and alleviating the skeletal defects induced by bone metastasis.
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PMID:Gentian violet inhibits MDA-MB-231 human breast cancer cell proliferation, and reverses the stimulation of osteoclastogenesis and suppression of osteoblast activity induced by cancer cells. 2626 90

Human melanomas contain a population of tumor-initiating cells that are able to maintain the growth of the tumor. We previously showed that the embryonic transcription factor SOX2 is essential for self-renewal and tumorigenicity of human melanoma-initiating cells. However, targeting a transcription factor is still challenging. Gentian violet (GV) is a cationic triphenylmethane dye with potent antifungal and antibacterial activity. Recently, a combination therapy of imiquimod and GV has shown an inhibitory effect against melanoma metastases. Whether and how GV affects melanoma cells remains unknown. Here we show that GV represses melanoma stem cell self-renewal through inhibition of SOX2. Mechanistically, GV hinders EGFR activation and inhibits the signal transducer and activator of transcription-3 [(STAT3)/SOX2] axis. Importantly, we show that GV treatment decreases STAT3 phosphorylation at residue tyrosine 705, thus preventing the translocation of STAT3 into the nucleus and its binding to SOX2 promoter. In addition, GV affects melanoma cell growth by promoting mitochondrial apoptosis and G2 cell cycle arrest. This study shows that in melanoma, GV affects both the stem cell and the tumor bulk compartments, suggesting the potential use of GV in treating human melanoma alone or in combination with targeted therapy and/or immunotherapy.
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PMID:Down-Regulation of SOX2 Underlies the Inhibitory Effects of the Triphenylmethane Gentian Violet on Melanoma Cell Self-Renewal and Survival. 2737 78