Berberis orthobotrys - A promising herbal anti-tumorigenic candidate for the treatment of pediatric alveolar rhabdomyosarcoma.

J Ethnopharmacol. 2018 Oct 11;229:262-271. doi: 10.1016/j.jep.2018.10.002. [Epub ahead of print] Adamus A1, Peer K1, Ali I2, Lisec J3, Falodun A4, Frank M5, Seitz G1, Engel N6. Author information 1 Department of Pediatric Surgery, University Hospital Marburg, Baldingerstraße, 35033 Marburg, Germany. 2 Department of Chemistry, Karakoram International University, 15100 Gilgit, Pakistan. 3 Division 1.7 Analytical Chemistry, Federal Institute for Materials Research and Testing (BAM), Richard-Willstätter-Straße 11, Berlin 12489 Germany. 4 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Benin, Benin City 300001, Nigeria. 5 Medical Biology and Electron Microscopy Centre, Rostock University Medical Center, Strempelstraße 14, Rostock 18057, Germany. 6 Department of Pediatric Surgery, University Hospital Marburg, Baldingerstraße, 35033 Marburg, Germany; Department of Oral and Maxillofacial Surgery, Facial Plastic Surgery, Rostock University Medical Center, Schillingallee 35, 18057 Rostock, Germany. Electronic address: nadja.engellutz@staff.uni-marburg.de. Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Berberis orthobotrys (BORM) is a medical plant with a long history in traditional usage for the treatment of wounds, cancer, gastrointestinal malady and several other diseases. Our previous studies identified the endemic Pakistani plant Berberis orthobotrys Bien. ex Aitch. as promising source for the treatment of breast cancer and osteosarcoma. AIM OF THE STUDY: The present study was aimed to evaluate the anti-cancer properties of 26 plant derived extracts and compounds including the methanolic root extract of Berberis orthobotrys (BORM) on pediatric alveolar rhabdomyosarcoma (RMA), which is known to develop drug resistance, metastatic invasion and potential tumor progression. MATERIALS AND METHODS: The main anti-tumor activity of BORM was verified by focusing on morphological, cell structural and metabolic alterations via metabolic profiling, cell viability measurements, flow cytometry, western blotting and diverse microscopy-based methods using the human RMA cell line Rh30. RESULTS: Exposure of 25 µg/ml BORM exerts an influence on the cell stability, the degradation of oncosomes as well as the shutdown of the metabolic activity of RMA cells, primarily by downregulation of the energy metabolism. Therefore glycyl-aspartic acid and N-acetyl serine decreased moderately, and uracil increased intracellularly. On healthy, non-transformed muscle cells BORM revealed very low metabolic alterations and nearly no cytotoxic impact. Furthermore, BORM is also capable to reduce Rh30 cell migration (~50%) and proliferation (induced G2/M cycle arrest) as well as to initiate apoptosis confirmed by reduced Bcl-2, Bax and PCNA expression and induced PARP-1 cleavage. CONCLUSIONS: The study provides the first evidence, that BORM treatment is effective against RMA cells with low side effects on healthy cells. Copyright © 2018 Elsevier B.V. All rights reserved. KEYWORDS: Alveolar rhabdomyosarcoma; Berberis orthobotrys; Metastasis; Oncosomes; Rh30; Stress fiber PMID: 30315865 DOI: 10.1016/j.jep.2018.10.002