Antiproliferative effect of plant cytokinin analogues with an inhibitory activity on cyclin-dependent kinases
Abstract
In this study, analogues of olomoucine, a previously described plant cytokinin analogue with cyclin-dependent kinase (CDK) inhibitory activity, were investigated for effect on CDK1 and CDK2 and for effect on cell proliferation. Eight new compounds exhibit stronger inhibitory activity on CDK1 and CDK2 and on cell proliferation than olomoucine. Some active compounds showed low inhibition of proliferation of normal myeloid growth. Improvement of inhibitory activity of known compounds with a C6-benzylamino group was brought about by substitution with one hydroxyl. Also, new C2 substituents associated with inhibitory activity on CDK and on cell proliferation are described. There was a significant correlation between effect on CDK and antiproliferative effect on the KG1 and Molt3 cell lines and on primary human lymphocytes, strongly suggesting that at least part of the antiproliferative effect of cytokinin analogues was due to inhibition of CDK activity. Cytokinin analogues induced apoptosis in a time- and concentration-dependent manner and changes in cell cycle distribution. The antiproliferative and pro-apoptotic effects of plant cytokinin analogues suggest that they are a new class of cytostatic agents and that they may find an application in the chemotherapy of cancer.
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Kinetin has a real potential power to reduce certain types of mammalian tumors.
“One of these cytokinins, kinetin, shows an antithrombotic activity [93] and a real potential power to reduce certain types of mammalian tumors [94].”
From Coconut water uses, composition and properties: a review (2012) · cites this paper as [94]
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Genetic alterations of cyclins, cyclin-dependent kinases, and Cdk inhibitors in human cancer
(1996) · Advances in cancer research · doi:10.1016/s0065-230x(08)60352-8 · Cited by 752 · see citing works
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The Chemical Composition and Biological Properties of Coconut (Cocos nucifera L.) Water
Yong, J. W. H., Ge, L., Ng, Y. F., & Tan, S. N. (2009) · Molecules · doi:10.3390/molecules14125144 · Cited by 753 · see citing works
Coconut water uses, composition and properties: a review
Prades, A., Dornier, M., Diop, N., & Pain, J.-P. (2012) · Fruits · doi:10.1051/fruits/2012002 · Cited by 284 · see citing works
Ge, L., Yong, J. W. H., Tan, S. N., Yang, X. H., & Ong, E. S. (2006) · Journal of Chromatography A · doi:10.1016/j.chroma.2006.08.027 · Cited by 55 · see citing works
CE for cytokinin analyses: A review
Ge, L., Tan, S., Yong, J. W. H., & Tan, S. N. (2006) · ELECTROPHORESIS · doi:10.1002/elps.200600195 · Cited by 23 · see citing works
Composition, Properties and Reactions of Coconut Water
Rethinam, P., & Krishnakumar, V. (2022) · Coconut Water · doi:10.1007/978-3-031-10713-9_4 · Cited by 9 · see citing works
Thakur, M., Pant, K., & Nanda, V. (2020) · Antioxidants in Vegetables and Nuts - Properties and Health Benefits · doi:10.1007/978-981-15-7470-2_19 · Cited by 5 · see citing works
- Authors
- Vermeulen, K., Strnad, M., Kryštof, V, Havlícěk, L., Van der Aa, A., Lenjou, M., Nijs, G., Rodrigus, I., Stockman, B., van Onckelen, H., Van Bockstaele, D., & Berneman, Z.
- Affiliations
- University of Antwerp (BE)
- Czech Academy of Sciences, Institute of Experimental Botany (CZ)
- Antwerp University Hospital (BE)
- Venue
- Leukemia
- Published
- 2002-03-01
- Volume
- 16
- Issue
- 3
- Pages
- 299-305
- ISSN
- 0887-6924 (ISSN-L)
- 1476-5551
- OpenAlex
- W2053755961
- Cited by
- 61
- References
- 1
- Citations by year
- 2024: 2 · 2023: 2 · 2022: 2 · 2021: 5 · 2020: 3 · 2019: 2 · 2018: 4 · 2017: 4 · 2015: 1 · 2014: 2 · 2013: 1 · 2012: 3
- FWCI
- 3.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Leukemia (publishedVersion)
- PubMed (publishedVersion)
- Document Server@UHasselt (UHasselt) (submittedVersion)
- Topics
- Physical Sciences › Chemistry › Organic Chemistry › Synthesis and biological activity
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Keywords
- olomoucine, cyclin-dependent kinase inhibition, CDK1, CDK2, antiproliferative activity, apoptosis, cell cycle distribution, cytostatic agents, cancer chemotherapy
- MeSH terms
- Cell Cycle, Cell Division, Colony-Forming Units Assay, Cytokinins, DNA, Neoplasm, Dose-Response Relationship, Drug, Enzyme Inhibitors, Kinetin, Leukemia, Plants, Purines, Time Factors, Tumor Cells, Cultured, CDC2 Protein Kinase, Apoptosis, Protein Serine-Threonine Kinases, Cyclin-Dependent Kinases, CDC2-CDC28 Kinases, Cyclin-Dependent Kinase 2
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