Polyphenolic Compounds from Lespedeza Bicolor Root Bark Inhibit Progression of Human Prostate Cancer Cells via Induction of Apoptosis and Cell Cycle Arrest
Sergey A. Dyshlovoy,
Darya Tarbeeva,
Sergey Fedoreyev,
Tobias Busenbender,
Moritz Kaune,
Marina Veselova,
Anatoliy Kalinovskiy,
Jessica Hauschild,
Valeria Grigorchuk,
Natalya Kim,
Carsten Bokemeyer,
Markus Graefen,
Petr Gorovoy,
Gunhild von Amsberg
Affiliations
Sergey A. Dyshlovoy
Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
Darya Tarbeeva
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-East Branch, Russian Academy of Sciences, Vladivostok 690022, Russia
Sergey Fedoreyev
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-East Branch, Russian Academy of Sciences, Vladivostok 690022, Russia
Tobias Busenbender
Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
Moritz Kaune
Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
Marina Veselova
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-East Branch, Russian Academy of Sciences, Vladivostok 690022, Russia
Anatoliy Kalinovskiy
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-East Branch, Russian Academy of Sciences, Vladivostok 690022, Russia
Jessica Hauschild
Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
Valeria Grigorchuk
Federal Scientific Center of the East Asia Terrestrial Biodiversity (Institute of Biology and Soil Science), Far Eastern Branch, Russian Academy of Sciences, Vladivostok 690022, Russia
Natalya Kim
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-East Branch, Russian Academy of Sciences, Vladivostok 690022, Russia
Carsten Bokemeyer
Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
Markus Graefen
Martini-Klinik, Prostate Cancer Center, University Hospital Hamburg-Eppendorf, 20251 Hamburg, Germany
Petr Gorovoy
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-East Branch, Russian Academy of Sciences, Vladivostok 690022, Russia
Gunhild von Amsberg
Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
From a root bark of Lespedeza bicolor Turch we isolated two new (7 and 8) and six previously known compounds (1−6) belonging to the group of prenylated polyphenols. Their structures were elucidated using mass spectrometry, nuclear magnetic resonance and circular dichroism spectroscopy. These natural compounds selectively inhibited human drug-resistant prostate cancer in vitro. Prenylated pterocarpans 1−3 prevented the cell cycle progression of human cancer cells in S-phase. This was accompanied by a reduced expression of mRNA corresponding to several human cyclin-dependent kinases (CDKs). In contrast, compounds 4−8 induced a G1-phase cell cycle arrest without any pronounced effect on CDKs mRNA expression. Interestingly, a non-substituted hydroxy group at C-8 of ring D of the pterocarpan skeleton of compounds 1−3 seems to be important for the CDKs inhibitory activity.
