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Open AccessArticle

Anticancer Activity of Amb4269951, a Choline Transporter-Like Protein 1 Inhibitor, in Human Glioma Cells

1
Institute of Medical Science, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan
2
Department of Molecular Preventive Medicine, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2020, 13(5), 104; https://doi.org/10.3390/ph13050104
Received: 9 May 2020 / Revised: 21 May 2020 / Accepted: 23 May 2020 / Published: 25 May 2020
(This article belongs to the Special Issue Novel Therapeutic Targets in Cancer)
Choline transporter-like protein 1 (CTL1) is highly expressed in glioma cells, and inhibition of CTL1 function induces apoptotic cell death. Therefore, CTL1 is a potential target molecule for glioma therapy. Here, we investigated the therapeutic mechanism underlying the antitumor effects of Amb4269951, a recently discovered novel CTL1 inhibitor, in the human glioma cell line U251MG, and evaluated its in vivo effects in a mouse xenograft model. Amb4269951 inhibited choline uptake and cell viability and increased caspase-3/7 activity. CTL1-mediated choline uptake is associated with cell viability, and the functional inhibition of CTL1 by Amb4269951 may promote apoptotic cell death via ceramide-induced suppression of the expression of survivin, an apoptotic inhibitory factor. Finally, Amb4269951 demonstrated an antitumor effect in a mice xenograft model by significantly inhibiting tumor growth without any weight loss. Amb4269951 is the lead compound in the treatment of glioma and exhibits a novel therapeutic mechanism. These results may lead to the development of novel anticancer drugs targeting the choline transporter CTL1, which has a different mechanism of action than conventional anticancer drugs against gliomas. View Full-Text
Keywords: glioma; choline; transporter; choline transporter-like protein; ceramide; survivin glioma; choline; transporter; choline transporter-like protein; ceramide; survivin
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MDPI and ACS Style

Watanabe, S.; Nishijima, N.; Hirai, K.; Shibata, K.; Hase, A.; Yamanaka, T.; Inazu, M. Anticancer Activity of Amb4269951, a Choline Transporter-Like Protein 1 Inhibitor, in Human Glioma Cells. Pharmaceuticals 2020, 13, 104.

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