Next Article in Journal
Synthesis and Fluorescent Properties of Novel Isoquinoline Derivatives
Previous Article in Journal
Effects of Orally Consumed Rosa damascena Mill. Hydrosol on Hematology, Clinical Chemistry, Lens Enzymatic Activity, and Lens Pathology in Streptozotocin-Induced Diabetic Rats
Previous Article in Special Issue
The Effect of Curcumin on the Differentiation of Mesenchymal Stem Cells into Mesodermal Lineage
Open AccessArticle

Curcumin Derivatives Verify the Essentiality of ROS Upregulation in Tumor Suppression

1
Laboratory of Tumor Cell Biology, Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Nara 630-0192, Ikoma, Japan
2
Laboratory of Synthetic Organic Chemistry, Division of Materials Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Nara 630-0192, Ikoma, Japan
3
Nagahama Institute of Bio-Science and Technology, Nagahama 526-0829, Shiga, Japan
4
Laboratory of Computational Systems Biology, Division of Information Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Nara 630-0192, Ikoma, Japan
5
Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia
*
Author to whom correspondence should be addressed.
Molecules 2019, 24(22), 4067; https://doi.org/10.3390/molecules24224067
Received: 4 October 2019 / Revised: 7 November 2019 / Accepted: 7 November 2019 / Published: 10 November 2019
(This article belongs to the Special Issue Curcumin)
Background: Curcumin has been shown to exert pleiotropic biological effects, including anti-tumorigenic activity. We previously showed that curcumin controls reactive oxygen species (ROS) levels through the ROS metabolic enzymes, to prevent tumor cell growth. In this study, we synthesized 39 novel curcumin derivatives and examined their anti-proliferative and anti-tumorigenic properties. Methods and Results: Thirty-nine derivatives exhibited anti-proliferative activity toward human cancer cell lines, including CML-derived K562 leukemic cells, in a manner sensitive to an antioxidant, N-acetyl-cysteine (NAC). Some compounds exhibited lower GI50 values than curcumin, some efficiently induced cell senescence, and others markedly increased ROS levels, efficiently induced cell death and suppressed tumor formation in a xenograft mouse model, without any detectable side effects. A clustering analysis of the selected compounds and their measurement variables revealed that anti-tumorigenic activity was most well-correlated with an increase in ROS levels. Pulldown assays and a molecular docking analysis showed that curcumin derivatives competed with co-enzymes to bind to the respective ROS metabolic enzymes and inhibited their enzymatic activities. Conclusions: The analysis of novel curcumin derivatives established the importance of ROS upregulation in suppression of tumorigenesis, and these compounds are potentially useful for the development of an anti-cancer drug with few side effects. View Full-Text
Keywords: curcumin; cancer; ROS; tumorigenicity; apoptosis; senescence; ROS metabolic enzymes curcumin; cancer; ROS; tumorigenicity; apoptosis; senescence; ROS metabolic enzymes
Show Figures

Figure 1

MDPI and ACS Style

Nakamae, I.; Morimoto, T.; Shima, H.; Shionyu, M.; Fujiki, H.; Yoneda-Kato, N.; Yokoyama, T.; Kanaya, S.; Kakiuchi, K.; Shirai, T.; Meiyanto, E.; Kato, J.-Y. Curcumin Derivatives Verify the Essentiality of ROS Upregulation in Tumor Suppression. Molecules 2019, 24, 4067.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop