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Menahydroquinone-4 Prodrug: A Promising Candidate Anti-Hepatocellular Carcinoma Agent

Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-180, Japan
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Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Stephen L. Chan
Diseases 2015, 3(3), 150-158; https://doi.org/10.3390/diseases3030150
Received: 20 May 2015 / Revised: 13 July 2015 / Accepted: 13 July 2015 / Published: 22 July 2015
(This article belongs to the Special Issue Targeted Therapy of Hepatocellular Carcinoma: Present and Future)
Recently, new therapeutics have been developed for hepatocellular carcinoma (HCC). However, the overall survival rate of HCC patients is still unsatisfactory; one of the reasons for this is the high frequency of recurrence after radical treatment. Consequently, to improve prognosis, it will be important to develop a novel anti-tumor agent that is especially effective against HCC recurrence. For clinical application, long-term safety, together with high anti-tumor efficacy, is desirable. Recent studies have proposed menahydroquinone-4 1,4-bis-N,N-dimethylglycinate hydrochloride (MKH-DMG), a prodrug of menahydroquinone-4 (MKH), as a promising candidate for HCC treatment including the inhibition of recurrence; MKH-DMG has been shown to achieve good selective accumulation of MKH in tumor cells, resulting in satisfactory inhibition of cell proliferation in des-γ-carboxyl prothrombin (DCP)-positive and DCP-negative HCC cell lines. In a spleen-liver metastasis mouse model, MKH-DMG has been demonstrated to have anti-proliferation and anti-metastatic effects in vivo. The characteristics of MKH-DMG as a novel anti-HCC agent are presented in this review article. View Full-Text
Keywords: vitamin K; hepatocellular carcinoma; anti-cancer drug; drug delivery; menaquinone-4 vitamin K; hepatocellular carcinoma; anti-cancer drug; drug delivery; menaquinone-4
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Enjoji, M.; Watase, D.; Matsunaga, K.; Kusuda, M.; Nagata-Akaho, N.; Karube, Y.; Takata, J. Menahydroquinone-4 Prodrug: A Promising Candidate Anti-Hepatocellular Carcinoma Agent. Diseases 2015, 3, 150-158.

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