4,5- Seco -5,10- friedo -abietane-type diterpenoids with anticancer activity from Salvia atropatana Bunge
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ORIGINAL ARTICLE
4,5-Seco-5,10-friedo-abietane-type diterpenoids with anticancer activity from Salvia atropatana Bunge Abolfazl Shakeri 1 & Seyedeh Sara Farahmand 1 & Zahra Tayarani-Najaran 2 & Seyed Ahmad Emami 1 & Norbert Kúsz 3 & Judit Hohmann 3 & Motahare Boozari 1 & Fatemeh Zaker Tavallaie 4 & Javad Asili 1,5 Received: 26 February 2020 / Accepted: 25 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract The purpose of this study is cytotoxicity-guided isolation of the petroleum ether fraction from the roots of Salvia atropatana for the first time, which has shown to growth inhibition and apoptosis induction in MCF-7 and PC3 cells. Bioassay-guided isolation method was conducted for finding compounds with highest cytotoxicity. Different extracts were prepared from the roots of Salvia atropatana. All extracts were tested for their cytotoxic activity against three cancer cell lines (PC3, MCF-7, and MDA-MB-231). The most cytotoxic extract was chosen for further isolation by column chromatography and HPLC. The chemical structures were determined by spectroscopic methods including 1D and 2D NMR. From the petroleum ether extract, four abietane-type diterpenoids, including a new abietane-type diterpenoid, named atropatanene (1), together with three known diterpenoids, 7αacetoxyroyleanone (2), and a mixture of two isomers, saprorthoquinone and aethiopinone (3+4), were isolated. The latter exhibited substantial cytotoxicity with IC50 value of 8.73 μg/ml against PC3 cells and led to an increasing number of cells in the subG1 region and an increase in the amount of Bax and cleavage of PARP protein, indicating apoptotic cell death. Owing to its numerous biological activities, Salvia species could be represented as a natural potential source against several cancer cell lines. Keywords Salvia genus . Bioassay-guided fractionation . Cytotoxicity . Diterpenoids . NMR . Western blot
Abolfazl Shakeri and Seyede Sara Farahmand contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00210-020-01967-2) contains supplementary material, which is available to authorized users. * Javad Asili
Motahare Boozari [email protected]
Abolfazl Shakeri [email protected]
Fatemeh Zaker Tavallaie [email protected]
Seyedeh Sara Farahmand [email protected]
1
Zahra Tayarani-Najaran [email protected]
Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
2
Seyed Ahmad Emami [email protected]
Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
3
Norbert Kúsz [email protected]
Department of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, Eötvös u. 6, Szeged H-6720, Hungary
4
Judit Hohmann [email protected]
Plant Biotechnology, Higher Education Complex of Shirvan, Shirvan, North Khorasan, Iran
5
Mashhad, Iran
Naunyn-Schmiedeberg's Arch Pharmacol
Introduction Naturally occurring compounds a
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