Abstract
Uncontrolled regulation of cyclin dependent kinases (CDKs) has negative implications in many cancers and malignancies and has recently led to the approval of select CDK inhibitors. Herein we present data reporting that xanthones, a class of compounds isolated from the purple mangosteen (Garcinia mangostana) fruit, can inhibit CDK2/CyclinE1. We evaluated nine different xanthones, including α-mangostin, β-mangostin, γ-mangostin, gartanin, 8-desoxygartanin, garcinone C, garcinone D, 9-hydroxycalabaxanthone, and 3-isomangostin for toxicity in 22Rν1 (prostate cancer cells) and MDA-MB-231 (breast cancer cells). All compounds dose-dependently inhibited the viability of both cell lines. A cell free biochemical assay was performed to determine if selected phytochemicals inhibited CDK2/CyclinE1. γ-Mangostin and α-mangostin were the strongest inhibitors, respectively. The results suggest that the position of key functional groups including hydroxyl and isoprenyl groups contribute to the CDK2 inhibitory effect. Taken together, the evidence suggests that xanthones can directly target CDK2 providing a possible explanation for their therapeutic potential.
References
Mar 21, 2002·Nature Reviews. Cancer·M Malumbres, M Barbacid
Aug 30, 2008·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·José Pedraza-ChaverriJazmin M Pérez-Rojas
Nov 1, 2008·Mini-reviews in Organic Chemistry·Young-Won Chin, A Douglas Kinghorn
Dec 14, 2011·Carcinogenesis·Jeremy J JohnsonHasan Mukhtar
May 12, 2012·Journal of Biomedicine & Biotechnology·Hitomi KuroseYoshinori Otsuki
Nov 13, 2012·Current Drug Targets·Atulkumar RamaiyaJeremy J Johnson
Jun 28, 2013·Frontiers in Pharmacology·Gongbo LiJeremy J Johnson
Aug 16, 2013·Nutrients·Fabiola Gutierrez-Orozco, Mark L Failla
Apr 30, 2014·Nutrition Research·Sakina M PetiwalaJeremy J Johnson
Mar 10, 2016·International Journal of Molecular Medicine·Hae Nim LeeJi Youn Jung
Mar 29, 2016·Molecular Nutrition & Food Research·Gongbo LiJeremy J Johnson
Oct 6, 2016·Oxidative Medicine and Cellular Longevity·Wichit SuthammarakWeerasak Muangpaisan
Jan 28, 2017·Nature Reviews. Cancer·Tobias Otto, Piotr Sicinski
Feb 9, 2017·Pharmacology & Therapeutics·Steven R WhittakerPaul A Clarke
Nov 15, 2017·Natural Product Research·Weiyi WangPeng Cai
Mar 8, 2018·Natural Product Research·Sabrin R M IbrahimGamal A Mohamed
Jun 2, 2018·Bioorganic & Medicinal Chemistry·Yiting WangJinhui Wang
Aug 18, 2018·International Journal of Molecular Sciences·Yunfeng ZhengKarl Wah Keung Tsim
Sep 1, 2018·ESMO Open·Matthias PreusserChristoph C Zielinski
Nov 15, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Agnieszka BartmańskaJoanna Wietrzyk
Nov 30, 2019·Molecular Carcinogenesis·Victor PhamXiaolin Zi
Jan 4, 2020·Cell Stress & Chaperones·Yan-Yun DingJian Zuo