Ctotoxic and apoptogenic effects of Perovskia abrotanoides flower extract on MCF-7 and HeLa cell lines

Document Type: Original Research Article


1 Department of Pharmacology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Pharmacological Research Center of Medicinal Plants, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

3 Pharmacological Research Center of Medicinal Plants, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran


Objective: Perovskia abrotanoides Karel, belongs to the family Lamiaceae and grows wild alongside the mountainous roads inarid and cold climate of Northern Iran. The anti-tumor activity of P. abrotanoides root extract has been shown previously. This study was designed to examine in vitro anti-proliferative and pro-apoptotic effects of flower extract of P. abrotanoides on MCF-7 and Hela cell lines.
Materials and Methods: Cells were cultured in DMEM medium with 10% fetal bovine serum, 100 units/ml penicillin and 100 µg/ml streptomycin and incubated with different concentrations of plant extracts. Cell viability was quantified by MTT assay. Apoptotic cells were determined using propidium iodide (PI) staining of DNA fragmentation by flow cytometry (sub-G1 peak).
Results: P. abrotanoides extract inhibited the growth of malignant cells in a time and dose-dependent manner and 1000 µg/ml of extract following 48h of incubation was the most cytotoxic dose against Hela cell in comparison with other doses; however, in MCF-7 cells,1000 and 500 µg/ml PA induced toxicity at all time points but with different features.. Analysis of flowcytometry histogram of treated cells compared with control cells indicated that the cytotoxic effect is partly due toapoptosis induction.
Conclusion: Hydro-alcoholic extract of P. abrotanoides flowers inhibits the growth of MCF-7 and HeLa cell lines, partly via inducing apoptosis. Their inhibitory effect was increased in a time and dose-dependent manner, especially in MCF7 cells. However, further studies are needed to reveal the mechanisms of P. abrotanoides extract-induced cell death.


Main Subjects

Abu-Dahab R, Abdallah MR, Kasabrik V, Mhaida NM  , Afifi, FU. 2015. Mechanistic studies of antiproliferative effects of Salvia triloba and Salvia dominica (Lamiaceae) on breast cancer cell lines (MCF7 and T47D). Z. Naturforsch, 69: 443-451.

Aoyagia, Y, Takahashit, Y, Satake, Y, Takeya, K, Aiyama, R, Matsuzaki, T, Hashimoto, S Kurihara, T. 2006. Cytotoxicity of abietane diterpenoids from Perovskia abrotanoides and of their semisynthetic analogues. Bioorg Med Chem, 14: 5285-5291.

Ashraf S N, Zubair M, Rizwan K, Tareen R B, Rasool N, Zia-Ul-Haq M,   Ercisli S. 2014. Compositional studies and biological activities of Perovskia abrotanoides Kar. oils. Biol Res, 47: 1-9.

Bai, A, Lu N, Guo Y,   Fan X. 2008. Tanshinone IIA ameliorates trinitrobenzene sulfonic acid (TNBS)-induced murine colitis. Dig Dis Sci, 53: 421-428.

Bandaranayake W M. 2006. Quality control, screening, toxicity, and regulation of herbal drugs. Modern phytomedicine: turning medicinal plants into drugs,PP. 25-58.

Beikmohammadi M. 2012. The evaluation of medicinal properties of Perovskia abrotanoides Karel. Middle-East J Sci Res, 11: 189-193.

Bolourian – Kashy M. 2007. Extraction, isolation, purification and structure elucidation of tanshinones from the dried roots of Perovskia abrotanoides Karel. Using spectroscopic methods and evaluation of their biological activity. pharmacy  signaling, university of Copenhagen, Denmark.

Choi MS, Cho DL, Choi HK, Im S Y, Ryu SY, Kim KM. 2004. Molecular mechanisms of inhibitory activities of tanshinones on Lipopolysaccharide-lnduced nitric oxide generation in RAW 264.7 cells. Arch Pharm Res, 27:1233-1237.

Dalkic E, Wang X, Wright N, Chan C. 2010. Cancer-drug associations: a complex system. PloS one, 5:, e10031.

Fan GW, Gao XM, Wang H, Zhu, Y, Zhang J, Hu, LM, Su, YF, Kang LY, Zhang BL. 2009. The anti-inflammatory activities of Tanshinone IIA, an active component of TCM, are mediated by estrogen receptor activation and inhibition of iNOS. J Steroid Biochem Mol Biol, 113: 275-280.

Fang J, Xu, SW, Wang P, Tang FT, Zhou SG, Gao, J, Chen JW, Huang HQ. Liu, PQ. 2010. Tanshinone II-A attenuates cardiac fibrosis and modulates collagen metabolism in rats with renovascular hypertension. Phytomedicine, 18: 58-64.

Fu J, Huang H, Liu, J, Pi R, Chen J, Liu P. 2007. Tanshinone IIA protects cardiac myocytes against oxidative stress-triggered damage and apoptosis. Eur J Pharmacol, 568: 213-221.

Hanahan D Weinberg R A. 2000. The hallmarks of cancer. cell, 100: 57-70.

Hazra B, Sarma M D Sanyal U. 2004. Separation methods of quinonoid constituents of plants used in Oriental traditional medicines. J Chromatogr, 812: 259-275.

Jiang B, Zhang L, Wang Y, Li M, Wu W, Guan S, Liu X, Yang M, Wang J, Guo DA. 2009. Tanshinone IIA sodium sulfonate protects against cardiotoxicity induced by doxorubicin in vitro and in vivo. Food and Chemical Toxicology(FCT), 47: 1538-1544.

Kim D H, Kim S, Jeon S J, Son, K H, Lee S, Yoon B H, Cheong J H, Ko K H Ryu J H. 2009. Tanshinone I enhances learning and memory, and ameliorates memory impairment in mice via the extracellular signal‐regulated kinase signalling pathway. Br J Pharmacol, 158: 1131-1142.

Kim E J, Jung SN, Son K H, Kim S R, Ha T Y, Park M G, Jo I G, Park J G, Choe W, Kim SS. 2007. Antidiabetes and antiobesity effect of cryptotanshinone via activation of AMP-activated protein kinase. Mol Pharmacol, 72: 62-72.

Lin R, Wang WR, Liu JT, Yang GD, Han CJ. 2006. Protective effect of tanshinone IIA on human umbilical vein endothelial cell injured by hydrogen peroxide and its mechanism. J Ethnopharmacol, 108: 217-222.

Farahmandbeigi M, Kadivar MR.2000. The incidence rate of registered cancer in Fars province . Disease Control Unit, Shiraz University Press, Iran.

Mazandarani M, Beykmohammadi M , Bayat H. 2010. Ethno pharmacology and investigation secondary metabolites of Perovskia abrotanoides Karel. in two natural regions, North of Iran. J Plant Sci Res, 4: 69-77.

Mousavi S H, Tavakkol-Afshari, J, Brook A, Jafari-Anarkooli I. 2009. Direct toxicity of Rose Bengal in MCF-7 cell line: role of apoptosis. Food Chem Toxicol, 47: 855-859.

Safaeighomi J, Batooli H. 2010. Determination of bioac tive molecules from flowers, leaves, stems and roots of Perovskia abrotanoides Karel growing in central Iran by nano scale injection. DIG J NANOMATER BIOS, 5: 551-556.

Sairafianpour M, Christensen J, Staerk D, Budnik B A, Kharazmi A, Bagherzadeh K, Jaroszewski J W. 2001. Leishmanicidal, antiplasmodial, and cytotoxic activity of novel diterpenoid 1, 2-quinones from Perovskia abrotanoides: new source of tanshinones. J  Nat  Prod , 64: 1398-1403.

Shu L, Cheung KL, Khor T O, Chen C, Kong AN. 2010. Phytochemicals: cancer chemoprevention and suppression of tumor onset and metastasis. Cancer and Metastasis Rev, 29: 483-502.

Yang L, Zou X, Ljang Q, Chen H, Feng J, Yan L, Wang Z, Zhou D, Li, S, Yao S. 2007. Sodium tanshinone ⅡA sulfonate depresses angiotensin Ⅱ-induced cardiomyocyte hypertrophy through MEK/ERK pathway. EXP MOL MED, 39: 65-73.

Zhou GY, Zhao BL, Hou JW, Ma, GE, Xin WJ. 1999. Protective efffects of sodium tanshinone IIA sulphate against adriamycin-induced lipid peroxidation in mice hearts in vivo and in vitro. Pharmacol Res, 40: 487-491.