image: The high conversion rate of curcumin prodrug TBP1901 to curcumin in bone marrow warrants its clinical application for diseases growing in the marrow like multiple myeloma and leukemia. The natural polyphenol curcumin has shown promising efficacy with tumors in a number of preclinical models. view more
Credit: KyotoU / Global Comms
Kyoto, Japan -- Curcumin, a natural molecule related to turmeric, has been used to treat cancer patients in cancer clinical studies. While it has documented antitumor effects, challenges involving its chemistry have caused drug development to lag.
Now, a team of researchers at Kyoto University has developed a prodrug form of curcumin, TBP1901, that has shown anti-tumor effects without toxicities.
"Curcumin has long been used as a spice or food coloring, so we expect to see minimal side effects," says lead author Masashi Kanai.
The natural polyphenol curcumin has shown promising efficacy with tumors in a number of preclinical models. Such studies have reported anecdotal evidence with cancer patients of curcumin's effect in oral form.
However, until now the poor bioavailability and low stability of curcumin have been roadblocks to its clinical application.
Kanai's team has found a possible detour around the problem by deductively identifying the enzyme GUSB for its key role in TBP1901 conversion to curcumin. The researchers hypothesized that this conversion would not be observed in mice with genetically impaired GUSB. They also confirmed, using a CRISPR-Cas9 screen method, that curcumin also has essential therapeutic targets.
"The high conversion rate of TBP1901 to curcumin in bone marrow warrants its clinical application for diseases growing in the marrow like multiple myeloma and leukemia," notes Kanai.
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The paper "Pharmacologic characterization of TBP1901, a prodrug form of aglycone curcumin, and CRISPR-Cas9 screen for therapeutic targets of aglycone curcumin" appeared on 10 October 2022 in European Journal of Pharmacology, with doi: 10.1016/j.ejphar.2022.175321
About Kyoto University
Kyoto University is one of Japan and Asia's premier research institutions, founded in 1897 and responsible for producing numerous Nobel laureates and winners of other prestigious international prizes. A broad curriculum across the arts and sciences at both undergraduate and graduate levels is complemented by numerous research centers, as well as facilities and offices around Japan and the world. For more information, please see: http://www.kyoto-u.ac.jp/en
Journal
European Journal of Pharmacology
Method of Research
Experimental study
Subject of Research
Animals
Article Title
Pharmacologic characterization of TBP1901, a prodrug form of aglycone curcumin, and CRISPR-Cas9 screen for therapeutic targets of aglycone curcumin
Article Publication Date
10-Oct-2022
COI Statement
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tadashi Hashimoto is the chief executive officer of Therabiopharma Inc. Atushi Imaizumi is the senior vice president of Therabiopharma Inc. Tomoyuki Abe, Hitomi Ozawa-Umeta, Atsuhiro Kishimoto, and Yasuhiro Katsuura are employees of Therabiopharma Inc. Masashi Kanai. and Hideaki Kakeya own equity and they are the scientific consultants of Therabiopharma Inc.