C I Delebinski1, S Georgi2, S Kleinsimon1, M Twardziok1, B Kopp3, M F Melzig2, G Seifert1. 1. Department of Paediatric Oncology/Haematology, Otto-Heubner-Centre for Paediatric and Adolescent Medicine (OHC), Charité, Universitaetsmedizin Berlin, Berlin, 13353, Germany. 2. FU Berlin, Institute for Pharmacy, Berlin, 14195, Germany. 3. Department of Pharmacognosy, University of Vienna, Vienna, A-1090, Austria.
Abstract
OBJECTIVES: Osteosarcoma is the most common type of malignant bone tumour in children and adolescents; it has poor prognosis, is highly metastatic and is resistant to current therapeutic approaches. In this study, different herbal extracts used in phytotherapy have been screened after searching innovative natural anti-cancer components. MATERIALS AND METHODS: Twenty steroid glycosides were examined for accordance to their potential of inhibiting cell proliferation and inducing apoptosis in the osteosarcoma cell line 143B. Cell proliferation was examined using a CASY counter. Effects of cardiac glycosides on induction of apoptosis were evaluated by Annexin V-APC and flow cytometry, caspase activity assay and measurement of mitochondrial membrane potential. RESULTS: The study revealed that various steroid glycosides suppress cell proliferation in a concentration-dependent manner. Further investigations indicated apoptotic induction by 17 of the 20 tested cardenolides and bufadienolides. Bufadienolide proscillaridin A, arenobufagin, and cardenolides evomonoside, convallatoxol and ouabain waged strongest apoptotic induction, associated with breakdown of mitochondrial membrane potential and activation of caspases -8 and -9. In contrast, the bufadienolide resibufogenin and cardenolide uzarin had no effect on proliferation inhibition, apoptotic induction or change in mitochondrial membrane potential. CONCLUSION: These results indicate that bufadienolides proscillaridin A and arenobufagin and cardenolide evomonoside, or related natural compounds might be promising new starting points for development of novel anti-cancer agents for treatment of osteosarcoma.
OBJECTIVES:Osteosarcoma is the most common type of malignant bone tumour in children and adolescents; it has poor prognosis, is highly metastatic and is resistant to current therapeutic approaches. In this study, different herbal extracts used in phytotherapy have been screened after searching innovative natural anti-cancer components. MATERIALS AND METHODS: Twenty steroid glycosides were examined for accordance to their potential of inhibiting cell proliferation and inducing apoptosis in the osteosarcoma cell line 143B. Cell proliferation was examined using a CASY counter. Effects of cardiac glycosides on induction of apoptosis were evaluated by Annexin V-APC and flow cytometry, caspase activity assay and measurement of mitochondrial membrane potential. RESULTS: The study revealed that various steroid glycosides suppress cell proliferation in a concentration-dependent manner. Further investigations indicated apoptotic induction by 17 of the 20 tested cardenolides and bufadienolides. Bufadienolideproscillaridin A, arenobufagin, and cardenolidesevomonoside, convallatoxol and ouabain waged strongest apoptotic induction, associated with breakdown of mitochondrial membrane potential and activation of caspases -8 and -9. In contrast, the bufadienolideresibufogenin and cardenolideuzarin had no effect on proliferation inhibition, apoptotic induction or change in mitochondrial membrane potential. CONCLUSION: These results indicate that bufadienolidesproscillaridin A and arenobufagin and cardenolideevomonoside, or related natural compounds might be promising new starting points for development of novel anti-cancer agents for treatment of osteosarcoma.
Authors: Huimin Gao; Martin Zehl; Hanspeter Kaehlig; Peter Schneider; Hermann Stuppner; Laetitia Moreno Y Banuls; Robert Kiss; Brigitte Kopp Journal: J Nat Prod Date: 2010-04-23 Impact factor: 4.050
Authors: Anne Mahringer; Shirin Karamustafa; Daniel Klotz; Stefan Kahl; V Badireenath Konkimalla; Yifen Wang; Junsong Wang; Hai-Yang Liu; Herbert Boechzelt; Xiaojiang Hao; Rudolf Bauer; Gert Fricker; Thomas Efferth Journal: Cancer Genomics Proteomics Date: 2010 Jul-Aug Impact factor: 4.069
Authors: Tatjana Mijatovic; Ute Jungwirth; Petra Heffeter; Mir Ali Reza Hoda; Rita Dornetshuber; Robert Kiss; Walter Berger Journal: Cancer Lett Date: 2009-03-31 Impact factor: 8.679
Authors: Felipe Finger Banfi; Karla de Sena Guedes; Carla Regina Andrighetti; Ana Carolina Aguiar; Bryan Wender Debiasi; Janaina da Costa Noronha; Domingos de Jesus Rodrigues; Gerardo Magela Vieira Júnior; Bruno Antonio Marinho Sanchez Journal: Korean J Parasitol Date: 2016-08-31 Impact factor: 1.341