Oncotarget

Research Papers:

A novel, nontoxic iron chelator, super-polyphenol, effectively induces apoptosis in human cancer cell lines

Toshiaki Ohara _, Yasuko Tomono, Xing Boyi, Sun Yingfu, Kazuhiro Omori and Akihiro Matsukawa

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Oncotarget. 2018; 9:32751-32760. https://doi.org/10.18632/oncotarget.25973

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Abstract

Toshiaki Ohara1,2, Yasuko Tomono3, Xing Boyi1, Sun Yingfu1, Kazuhiro Omori4 and Akihiro Matsukawa1

1Department of Pathology & Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

2Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

3Shigei Medical Research Institute, Okayama, Japan

4Department of Periodontics and Endodontics, Okayama University Hospital, Okayama, Japan

Correspondence to:

Toshiaki Ohara, email: t_ohara@cc.okayama-u.ac.jp

Keywords: iron; chelation; chelator; apoptosis; toxicity

Received: April 11, 2017    Accepted: July 29, 2018    Published: August 28, 2018

ABSTRACT

Iron chelation therapy is the main treatment for iron overload disease. Iron chelators were recently reported to be useful for cancer therapy; however, they cause side effects that make them difficult to use in some cancer patients. Thus, a novel oral iron chelator, super-polyphenol (SP), was developed for cancer therapy to decrease the side effects. SP is either water soluble or insoluble, and has different isoforms according to the number of side chains. Of these isoforms, water-soluble SP6 and SP10 appear to be the best candidates, as they have the strongest chelating abilities. In this study, we focused on the usefulness and safety of SP6 and SP10 as anti-cancer drugs, and examined their anti-cancer effects and toxicity. The results showed that SP6 and SP10 inhibited cancer cell proliferation by inducing apoptosis in HCT116, HSC-2, A549, and MCF-7 cancer cells. SP10 also inhibited tumor growth in an HCT116 xenograft model. SP6 and SP10 had no acute toxicities. An intravenous injection test revealed that SP6 and SP10 had better safety profiles than the iron chelator deferoxamine. In conclusion, SP is a novel oral iron chelator with anti-cancer effects and few adverse side effects. This is the first report of SP in the literature.


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