Skip to main content

Advertisement

SpringerLink
Log in

Effects of Salvia officinalis L. on 7, 12-dimethylbenz[a]anthracene-induced breast cancer in rats and mouse mammary carcinoma cells (4T1)

  • Original Article
  • Published:
Comparative Clinical Pathology Aims and scope Submit manuscript

Abstract

The toxicity of Salvia officinalis L. on different cancer cell lines has been reported extensively, but an in vivo evaluation on breast cancer has not been conducted. Therefore, in vivo and in vitro studies of are evaluated in this study. The hydro-alcoholic extract of Salvia officinalis L. was studied in female Wistar rats in three groups: one control (Con) group (n = 7) and two 7, 12-dimethylbenz[a]anthracene cancer-induced groups (CI) that were gavaged either with distilled water (Con-CI) or 30 mg/kg sage hydro-alcoholic extract (SHE-CI) for 30 days (n = 34). A mammary gland whole mount was prepared, and the number of alveolar buds and lobules were scored. Histomorphometrical changes and apoptosis were examined in mammary gland sections. Chromatin condensation, cell viability, apoptosis, and toxicity induction were monitored in 4T1 mouse mammary carcinoma cells treated by different doses of SHE. IC50 of the 4T1 cell-treated SHE were examined by MTT assay. A decrease in alveolar buds, number of ducts and lobules, ductal diameters, and epithelial cells was observed in whole mount and histological sections of mammary glands in SHE-CI compared to the Con-CI group. Apoptotic cells were increased in SHE-CI compared to the Con-CI group. A decrease in cell viability and increase in chromatin condensation were observed in a dose-dependent manner in SHE-treated cultures. MTT assay revealed IC50 of the 4T1 cell-treated SHE reduced significantly compared to the NIH cell line from the fibroblast as a normal cell. Salvia officinalis might prevent breast cancer under both in vivo and in vitro conditions.

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
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  • Adlercreutz H, Bannwart C, Wahala K, Makela T, Brunow G, Hase T (1993) Inhibition of human aromatase by mammalian lignans and isoflavonoid phytoestrogens. J Steroid Biochem Mol Biol 44:147–153

    Article  CAS  PubMed  Google Scholar 

  • Ayatollahi A, Shojaii A, Kobarfard F, Mohammadzadeh M, Choudhary M (2009) Two flavones from Salvia leriaefolia. Iran J Pharmcol Res 8:179–184

    CAS  Google Scholar 

  • Balogh GA, Russo IH, Russo J (2003) Mutations in mismatch repairs genes are involved in the neoplastic transformation of human breast epithelial cells. Intl Oncol 23:411–419

    CAS  Google Scholar 

  • Bancroft JD, Stevens A (1991) Theory and practice of histological techniques, third edn. Churchill Livingstone, Edinburgh

    Google Scholar 

  • Baranauskiene R, Dambrauskiene E, Venskutonis P, Baranauskiene R, Dambrauskiene E, Venskutonis P (2011) Influence of harvesting time on the yield and chemical composition of sage (Salvia officinalis L.). Foodbalt 104–109

  • Bauer J, Kuehnl S, Rollinger JM, Scherer O, Northoff H, Stuppner H, Werz O, Koeberle A (2012) Carnosol and carnosic acids from Salvia officinalis inhibit microsomal prostaglandin E2 synthase-1. Pharmacol Exper Thera 342:169–176

    Article  CAS  Google Scholar 

  • Deeb SJ, El-Baba CO, Hassan SB, Larsson RL, Gali-Muhtasib HU (2011) Sage components enhance cell death through nuclear factor kappa-B signaling. Front Biosci 1:410–420

    Google Scholar 

  • Franek KJ, Zhou Z, Zhang WD, Chen WY (2005) In vitro studies of baicalin alone or in combination with salvia miltiorrhiza extract as a potential anti-cancer agent. Int J Oncol 26:217–224

    CAS  PubMed  Google Scholar 

  • Hadri A, Gomez Del Rio M, Sanz J, Coloma A, Idaomar M, Ozanas B, González J, Reus M (2012) Cytotoxic activity of α-humulene and transcaryo-phyllene from Salvia officinalis in animal and human tumor cells. An R Acad Nac Farm 76:343–356

    Google Scholar 

  • Hamidpour M, Hamidpour R, Hamidpour S, Shahlari M (2014) Chemistry, pharmacology, and medicinal property of sage (Salvia) to prevent and cure illnesses such as obesity, diabetes, depression, dementia, lupus, autism, heart disease, and cancer. J Tradit Complement Med 4:82–88

    Article  PubMed  PubMed Central  Google Scholar 

  • Jackson SJT, Singletary KW (2004) Sulforaphane: a naturally occurring mammary carcinoma mitotic inhibitor, which disrupts tubulin polymerization. Carcinogenesis 25:219–227

    Article  CAS  PubMed  Google Scholar 

  • Janicsak G, Zupko I, Nikolovac MT, Forgo P, Vasas A, Mathe I, Blunden G, Hohmann J (2011) Bioactivity-guided study of anti-proliferative activities of Salvia extracts. Nat Prod Commun 6:575–579

    CAS  PubMed  Google Scholar 

  • Jedinak A, Muckova M, Kost’alova D, Maliar T, Masterova I (2006) Antiprotease and antimetastatic activity of ursolic acid isolated from Salvia officinalis. Z Naturforsch C 61:777–782

    Article  CAS  PubMed  Google Scholar 

  • Kurzer M, Xu X (1997) Dietary phytoestrogens. Annu Rev Nutr 17:353–381

    Article  CAS  PubMed  Google Scholar 

  • Lamartiniere CA, Cotroneo MS, Fritz WA, Wang J, Mentor-Marcel R, Elgavish A (2002) Genistein chemoprevention: timing and mechanisms of action in murine mammary and prostate. Nutr 132:552S–558S

    Google Scholar 

  • Lilla JN, Werb Z (2010) Mast cell contribute to the stromal microenvironment in mammary gland branching morphogenesis. Dev Biol 337:124–133

    Article  CAS  PubMed  Google Scholar 

  • Ma H, Carpenter CL, Sullivan-Halley J, Bernstein L (2011) The roles of herbal remedies in survival and quality of life among long-term breast cancer survivors-results of a prospective study. BMC Cancer 11:222

    Article  PubMed  PubMed Central  Google Scholar 

  • Magee PJ, Rowland AI (2004) Phyto-oestrogens, their mechanism of action: current evidence for a role in breast and prostate cancer. Br J Nutr 91:513–531

    Article  CAS  PubMed  Google Scholar 

  • Manni A, Trujillo JE, Pearson OH (1977) Predominant role of prolactin in stimulating the growth of 7,12-dimethylbenza(a)anthracene-induced rat mammary tumor. Cancer Res 37:1216–1219

    CAS  PubMed  Google Scholar 

  • Monsefi M, Azarbahram Z, Abedian A, Ashraf MJ (2015) Salvia officinalis induce alveolar bud growing in adults female rat mammary glands. Avecinna J phytomed 5:560–567

    Google Scholar 

  • Nelson KG, Takahashi T, Lee DC (1992) Transforming growth factor-a is a potential mediator of estrogen action in themouse uterus. Endocrinol 131:1657–1664

    Article  CAS  Google Scholar 

  • Ososki A, Kennelly EJ (2003) Phytoestrogens: a review of the present state of research. Phytother Res 17:845–869

    Article  CAS  PubMed  Google Scholar 

  • Petrakis NL, Barnes S, King EB, Lowenstein J, Wiencke J, Miike R, Kirk M, Coward L (1996) Stimulatory influence of soy protein isolate on breast secretion in pre-and post-menopausal women. Cancer Epidemo Biomarkers Orev 5;785–794

  • Pozo-Guisado E, Merino JM, Mulero-Navarro S, Lorenzo-Benayas MJ, Centeno F, Alvarez-Barrientos A, Fernandez Salguero PM (2005) Resveratrol-induced apoptosis in MCF-7 human breast cancer cells involves a caspase-independent mechanism with downregulation of Bcl-2 and NF-kappaB. Int J Cancer 115:74–84

    Article  CAS  PubMed  Google Scholar 

  • Russo H, Russo J (1996) Mammary gland neoplasia long term rodent studies. Environ Health Perspect 104:938–967

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Russo J, Hasan Lareef M, Balogh G, Guo S, Russo IH (2003) Estrogen and its metabolites are carcinogenic agents in human breast epithelial cells. J Steroid Biochem Mol Biol 87:1–25

    Article  CAS  PubMed  Google Scholar 

  • Sakarkar DM, Deshmukh VN (2011) Ethnopharmacological review of traditional medicinal plants for anti-cancer activity. Intern J Pharm Tech Res 3:298–308

    Google Scholar 

  • Walch S, Tinzoh L, Zimmerman B, Stuhlinger W, Lachenmeier D (2011) Antioxidant capacity and polyphenolic composition as quality indicators for aqueous infusions of Salvia officinalis L. Front Pharmacol 2:29

    Article  Google Scholar 

  • Xavier C, Lima C, Fernandes-Ferreira M, Pereira-Wilson C (2009) Salvia fruticosa, Salvia officinalis, and Rosmarinic acid induce apoptosis and inhibit proliferation of human colorectal cell lines: the role in MAPK/ERK pathway. Nut Cancer 61:564–571

    Article  CAS  Google Scholar 

  • Yurtseven S, Cetin M, Sengiil T, Sogut B (2008) Effect of sage extract (Salvia officinalis) on growth performance, blood parameters, oxidative stress and DNA damage in partridges. South Afr J Animal Sci 38:145–152

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biology, School of Sciences, Shiraz University, Shiraz, Iran

    Malihezaman Monsefi, Zahra Azarbahram, Mehrnaz Abedian & Sara Behrozimoghadam

  2. College of Sciences, Shiraz University, Shiraz, Iran

    Malihezaman Monsefi

  3. Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Mohammad Javad Ashraf

Authors
  1. Malihezaman Monsefi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zahra Azarbahram
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mehrnaz Abedian
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sara Behrozimoghadam
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mohammad Javad Ashraf
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Malihezaman Monsefi.

Ethics declarations

Funding

This study was funded by the Vice-Chancellery for Research of Shiraz University.

Declaration of interest

The authors declare that they have no conflict of interest.

Ethical approval

The animal experiments were approved by the Institutional Animal Ethics and Health Committee of the Biology Department of Shiraz University and were performed according to the principles of the care and use of laboratory animals established by the National Institute of Health.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Monsefi, M., Azarbahram, Z., Abedian, M. et al. Effects of Salvia officinalis L. on 7, 12-dimethylbenz[a]anthracene-induced breast cancer in rats and mouse mammary carcinoma cells (4T1). Comp Clin Pathol 26, 1003–1015 (2017). https://doi.org/10.1007/s00580-017-2476-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00580-017-2476-5

Keywords

Search

Navigation