Skip to main content
SpringerLink
Log in

Cytotoxicity, apoptosis inducing activity and Western blot analysis of tanshinone derivatives from Stachys parviflora on prostate and breast cancer cells

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Cytotoxic activities of methanolic crude extract of Stachys parviflora (Lamiaceae family) and its sub-fractions were primarily evaluated against human breast adenocarcinoma (MCF-7 and MDA-MB-231) and prostate (PC3) cell lines. The methanolic extract exhibited the highest activity, and was chosen for the isolation procedure. Four diterpenoid quinones, namely miltirone [1], tanshinone IIA [2], 1-hydroxy-tanshinone IIA [3], and cryptotanshinone [4] were isolated. Notably, this is the first report on the isolation and/or characterization of the mentioned diterpenoids from the Stachys genus. In this study, 1-hydroxy-tanshinone IIA [3] displayed the highest cytotoxicity among the isolated compounds. The mechanism of the cytotoxicity of methanolic extract and isolated compounds was further investigated by the utilization of propidium iodide staining (PI) assay. The results showed that the methanolic extract and 1-hydroxy-tanshinone IIA [3] enhanced DNA fragmentation in PC3 and MCF-7 cells. Moreover, the western blotting analysis demonstrated increasing and decreasing protein levels of Bax and Bcl2, respectively, and cleaved poly ADP-ribose polymerase (PARP). Further bioassay-guided phytochemical assessments of S. parviflora can be suggested as a promising approach for discovering potent bioactive secondary metabolites.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Tamokou JDD, Mbaveng AT, Kuete V (2017) In: Kuete V (ed) Chap. 8 - Antimicrobial activities of african medicinal spices and vegetables; in Medicinal Spices and Vegetables from Africa. Academic Press, pp 207–237

  2. Tomou EM, Barda C, Skaltsa H (2020) Genus Stachys: A review of traditional uses, phytochemistry and bioactivity. Med (Basel) 7:63–136

    CAS  Google Scholar 

  3. Shakeri A, D’Urso G, Taghizadeh SF et al (2019) LC-ESI/LTQOrbitrap/MS/MS and GC-MS profiling of Stachys parviflora L. and evaluation of its biological activities. J Pharm Biomed Anal 168:209–216

    Article  CAS  Google Scholar 

  4. Ahmad VU, Arshad S, Bader S, Ahmed A, Iqbal S, Tareen RB (2006) New phenethyl alcohol glycosides from Stachys parviflora. J Asian Nat Prod Res 8:105–111

    Article  CAS  Google Scholar 

  5. Ahmad VU, Arshad S, Bader S et al (2008) New terpenoids from Stachys parviflora Benth. Magn Reson Chem 46:986–989

    Article  CAS  Google Scholar 

  6. Ahmad VU, Arshad S, Bader S et al (2007) A new triterpenoidal saponin and a flavone glycoside from Stachys parviflora. Nat Prod Commun 2:889–894

    CAS  Google Scholar 

  7. Farooq U, Naz S, Sarwar R et al (2015) Isolation and characterization of two new diterpenoids from Stachys parviflora: Antidiarrheal potential in mice. Phytochem Lett 14:198–202

    Article  CAS  Google Scholar 

  8. Farooq U, Ayub K, Hashmi MA et al (2015) A new rosane-type diterpenoid from Stachys parviflora and its density functional theory studies. Nat Prod Res 29:813–819

    Article  CAS  Google Scholar 

  9. Farooq U, Ayub K, Hashmi MA et al (2015) Spectroscopic and density functional theory studies of a new rosane type diterpenoid from Stachys parviflora. Rec Nat Prod 9:329–335

    CAS  Google Scholar 

  10. Ahmad V, Arshad S, Bader S, Iqbal S, Tareen B (2005) Stachyfloroside E: A New Acylated Flavone Glycoside from Stachys parviflora. Cheminform 36:1–1

    Google Scholar 

  11. Bashi D, Emami S, Iranshahi M, Asili J (2013) Essential Oil Composition of Aerial Parts of Stachys parviflora L. from Iran. J Essent Oil-Bear Plants 16:261–264

    Article  CAS  Google Scholar 

  12. Bashi D, Attaran S, Fazly Bazzaz BS, Khanzadeh F, Soheili V, Mohammadpour A (2016) Evaluation, prediction and optimization the ultrasoundassisted extraction method using response surface methodology: Antioxidant and biological properties of Stachys parviflora L. Iran J Basic Med Sci 19:829–841

    Google Scholar 

  13. Shakeri A, Farahmand S, Tayarani-Najaran Z et al (2020) 4,5-Seco-5,10-friedo-abietane-type diterpenoids with anticancer activity from Salvia atropatana Bunge. Naunyn-Schmiedeb Arch Pharmacol 394:241–248

    Article  Google Scholar 

  14. Eghbaliferiz S, Emami SA, Tayarani-Najaran Z et al (2018) Cytotoxic diterpene quinones from Salvia tebesana Bunge. Fitoterapia 128:97–101

    Article  CAS  Google Scholar 

  15. Riccardi C, Nicoletti I (2006) Analysis of apoptosis by propidium iodide staining and flow cytometry. Nat Protoc 1:1458–1461

    Article  CAS  Google Scholar 

  16. Mousavi SH, Motaez M, Zamiri-Akhlaghi A, Emami SA, Tayarani-Najaran Z (2014) In-vitro Evaluation of Cytotoxic and Apoptogenic Properties of Sophora Pachycarpa. Iran J Pharm Res 13:665–673

    PubMed  PubMed Central  Google Scholar 

  17. Niu J, Li C, Wu H et al (2015) Propidium iodide (PI) stains Nissl bodies and may serve as a quick marker for total neuronal cell count. Acta Histochem 117:182–187

    Article  CAS  Google Scholar 

  18. Mahmood T, Yang P-C (2012) Western blot: technique, theory, and trouble shooting. N Am J Med 4:429–434

    Article  Google Scholar 

  19. Hayashi T, Kakisawa H, Hsū H-Y, Chen YP (1970) The structure of miltirone, a new diterpenoid quinone.J Chem Soc. D:299a-299a

  20. Mothana RA, Jansen R, Gruenert R, Bednarski PJ, Lindequist U (2009) Antimicrobial and cytotoxic abietane diterpenoids from the roots of Meriandera benghalensis (Roxb.) Benth. Pharmazie 64:613–615

    CAS  PubMed  Google Scholar 

  21. Kakisawa H, Hayashi T, Okazaki I, Ohashi M (1968) Isolation and structures of new tanshinones. Tetrahedron Lett 9:3231–3234

    Article  Google Scholar 

  22. Chen W-S, Jia X-m, Zhang W-d, Lou Z-y, Qiao C-z (2003) Chemical constituents in the roots of Salvia przewalskii Maxim. Yao xue xue bao = Acta pharm Sin. 38:354–357

  23. Gezici S, Şekeroğlu N (2019) Current perspectives in the application of medicinal plants against cancer: novel therapeutic agents. Anticancer Agents Med Chem 19:101–111

    Article  CAS  Google Scholar 

  24. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424

    Article  Google Scholar 

  25. Fahad Ullah M (2019) In: Ahmad A (ed) Breast Cancer: Current Perspectives on the Disease Status; in Breast Cancer Metastasis and Drug Resistance: Challenges and Progress. Springer International Publishing, Cham, pp 51–64

    Chapter  Google Scholar 

  26. Guan R, Van Le Q, Yang H et al (2021) A review of dietary phytochemicals and their relation to oxidative stress and human diseases. Chemosphere 271:129499–129512

    Article  CAS  Google Scholar 

  27. Shakeri A, Masullo M, D’Urso G et al (2018) In depth chemical investigation of Glycyrrhiza triphylla Fisch roots guided by a preliminary HPLC-ESIMS(n) profiling. Food Chem 248:128–136

    Article  CAS  Google Scholar 

  28. Rawla P (2019) Epidemiology of prostate cancer. World J Oncol 10:63–89

    Article  CAS  Google Scholar 

  29. Fang Z-Y, Zhang M, Liu J-N, Zhao X, Zhang Y-Q, Fang L (2021) Tanshinone IIA: A Review of its Anticancer Effects. Front Pharmacol 11:611087–611087

    Article  Google Scholar 

  30. Li H, Gao C, Liu C et al (2021) A review of the biological activity and pharmacology of cryptotanshinone, an important active constituent in Danshen. Biomed Pharmacother 137:111332–111343

    Article  CAS  Google Scholar 

  31. Kai G, Xu H, Zhou C et al (2011) Metabolic engineering tanshinone biosynthetic pathway in Salvia miltiorrhiza hairy root cultures. Metab Eng 13:319–327

    Article  CAS  Google Scholar 

  32. Kalita R, Patar L, Shasany AK, Modi MK, Sen P (2015) Molecular cloning, characterization and expression analysis of 3-hydroxy-3-methylglutaryl coenzyme A reductase gene from Centella asiatica L. Mol Biol Rep 42:1431–1439

    Article  CAS  Google Scholar 

  33. Xu H, Zhang L, Zhou C, Xiao J, Liao P, Kai G (2011) Metabolic regulation and genetic engineering of pharmaceutical component tanshinone biosynthesis in Salvia miltiorrhiza. J Med Plant Res 4:2591–2597

    Google Scholar 

  34. Shi M, Luo X, Ju G et al (2016) Enhanced diterpene tanshinone accumulation and bioactivity of transgenic Salvia miltiorrhiza hairy roots by pathway engineering. J Agric Food Chem 64:2523–2530

    Article  CAS  Google Scholar 

  35. Lee CM, Wong HN, Chui KY, Choang TF, Hon PM, Chang HM (1991) Miltirone, a central benzodiazepine receptor partial agonist from a Chinese medicinal herb Salvia miltiorrhiza. Neurosci Lett 127:237–241

    Article  CAS  Google Scholar 

  36. Kumar S, Pandey AK (2013) Chemistry and biological activities of flavonoids: an overview. Sci World J. 2013: 162750–162766

  37. Fu L, Han B, Zhou Y et al (2020) The anticancer properties of tanshinones and the pharmacological effects of their active ingredients. Front Pharmacol 11:193–210

    Article  CAS  Google Scholar 

  38. Yan MY, Chien SY, Kuo SJ, Chen DR, Su CC (2012) Tanshinone IIA inhibits BT-20 human breast cancer cell proliferation through increasing caspase 12, GADD153 and phospho-p38 protein expression. Int J Mol Med 29:855–863

    CAS  PubMed  Google Scholar 

  39. Wu c-f and, Efferth T (2017) Anticancer Activity of Salvia miltiorrhiza and Its Secondary Metabolites;. Springer, Cham. in Salvia Biotechnology 179–207

    Google Scholar 

  40. Song W, Ma YY, Miao S et al (2019) Pharmacological actions of miltirone in the modulation of platelet function. Acta Pharmacol Sin 40:199–207

    Article  CAS  Google Scholar 

  41. Liu S, Han Z, Trivett AL et al (2019) Cryptotanshinone has curative dual anti-proliferative and immunotherapeutic effects on mouse Lewis lung carcinoma. Cancer Immunol Immunother 68:1059–1071

    Article  CAS  Google Scholar 

  42. Lu L, Zhang S, Li C et al (2017) Cryptotanshinone inhibits human glioma cell proliferation in vitro and in vivo through SHP-2-dependent inhibition of STAT3 activation. Cell Death Dis 8:e2767–e2767

    Article  CAS  Google Scholar 

  43. Saraf RS, Datta A, Sima C, Hua J, Lopes R, Bittner M (2018) An in-silico study examining the induction of apoptosis by cryptotanshinone in metastatic melanoma cell lines. BMC Cancer 18:855–867

    Article  Google Scholar 

  44. Shen L, Zhang G, Lou Z, Xu G, Zhang G (2017) Cryptotanshinone enhances the effect of Arsenic trioxide in treating liver cancer cell by inducing apoptosis through downregulating phosphorylated- STAT3 in vitro and in vivo. BMC Complement Altern Med 17:106–114

    Article  Google Scholar 

Download references

Acknowledgements

This research was supported by the Mashhad University of Medical Sciences (950763) Research Council.

Author information

Authors and Affiliations

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

    Abolfazl Shakeri, Motahare Boozari & Javad Asili

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

    Toktam Hafezian

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

    Norbert Kúsz & Judit Hohmann

  4. Institute of Pharmacy/Pharmacognosy, Center for Molecular Biosciences (CMBI), University of Innsbruck, Innrain 80–82, 6020, Innsbruck, Austria

    Javad Mottaghipisheh

  5. Department of Traditional Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Seyed Ahmad Emami

  6. Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Zahra Tayarani-Najaran

Authors
  1. Abolfazl Shakeri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Toktam Hafezian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Norbert Kúsz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Judit Hohmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Motahare Boozari
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Javad Mottaghipisheh
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Seyed Ahmad Emami
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zahra Tayarani-Najaran
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Javad Asili
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Zahra Tayarani-Najaran or Javad Asili.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Consent for publication

All authors approved the publication.

Research involving human participants and/or animalsn

This article does not contain any studies with human participants and/or animals performed by any of the authors.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shakeri, A., Hafezian, T., Kúsz, N. et al. Cytotoxicity, apoptosis inducing activity and Western blot analysis of tanshinone derivatives from Stachys parviflora on prostate and breast cancer cells. Mol Biol Rep 49, 8251–8258 (2022). https://doi.org/10.1007/s11033-022-07541-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-022-07541-8

Keywords

Search

Navigation