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4,5-Seco-5,10-friedo-abietane-type diterpenoids with anticancer activity from Salvia atropatana Bunge

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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, 7α-acetoxyroyleanone (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.

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Funding

This work was financially supported by grants from the Mashhad University of Medical Sciences Research Council (grant number 930776). Financial supports from the Economic Development and Innovation Operative Programme GINOP-2.3.2-15-2016-00012 and Ministry of Human Capacities Hungary grant 20391-3/2018/FEKUSTRAT are gratefully acknowledged.

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Author notes

  1. Abolfazl Shakeri and Seyede Sara Farahmand contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Abolfazl Shakeri, Seyedeh Sara Farahmand, Seyed Ahmad Emami, Motahare Boozari & Javad Asili

  2. Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Zahra Tayarani-Najaran

  3. Department of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, Eötvös u. 6, Szeged, H-6720, Hungary

    Norbert Kúsz & Judit Hohmann

  4. Plant Biotechnology, Higher Education Complex of Shirvan, Shirvan, North Khorasan, Iran

    Fatemeh Zaker Tavallaie

  5. Mashhad, Iran

    Javad Asili

Authors
  1. Abolfazl Shakeri
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  2. Seyedeh Sara Farahmand
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  3. Zahra Tayarani-Najaran
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  4. Seyed Ahmad Emami
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Contributions

ASh, JA, and ZTN conceived and designed research. SSF, MB, and FZT carried out experiments and analyzed data. ASh and NK wrote the manuscript. SAE and JH reviewed and edited the draft. All authors read and approved the final published version of the manuscript.

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NMR and HRMS spectra of compound 1 are provided.

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Shakeri, A., Farahmand, S.S., Tayarani-Najaran, Z. et al. 4,5-Seco-5,10-friedo-abietane-type diterpenoids with anticancer activity from Salvia atropatana Bunge. Naunyn-Schmiedeberg's Arch Pharmacol 394, 241–248 (2021). https://doi.org/10.1007/s00210-020-01967-2

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