Promising anticancer activity of Cyclotrichium niveum L. extracts through induction of both apoptosis and necrosis.

In this study, cytotoxic effects of the dichloromethane, ethyl acetate, ethanol, and aqueous extracts of the aerial parts of Cyclotrichium niveum (Boiss.) Manden. & Scheng (Lamiaceae) were evaluated. We tested HeLa, MCF-7 cancer cells, and MRC-5 and MCF-10A normal cells. The ethyl acetate and dichloromethane extracts induced cytotoxicity whereas the ethanol and aqueous extracts had no cytotoxic activity against both cancer cells. IC50 values of the dichloromethane extract were 353.0 ± 84.30 μg/ml, 114.8 ± 40.34 μg/ml, 39 ± 0.56 μg/ml, and 49 ± 13 μg/ml in HeLa, MCF-7, MRC-5, MCF-10A cells, respectively. IC50 values of the ethyl acetate extract were 117.0 ± 36.24 μg/ml in HeLa cells, 156.3 ± 19.86 μg/ml in MCF-7 cells, 1100 ± 340 μg/ml in MRC-5 cells and 7900 ± 1200 μg/ml in MCF-10A cells. Additionally, the ethyl acetate extract showed more selectivity to HeLa and MCF-7 cancer cells than MRC-5 and MCF-10A normal cells. Our results of HPLC analysis showed that apigenin in the ethyl acetate extract (2.2518 ± 0.0005 mg/100 mg extract) might be responsible of that selective cytotoxic effect. In the current work, we have shown for the first time that C. niveum has cytotoxic properties in the cancer cell lines tested.

[1]  G. Haegeman,et al.  Screening of indigenous Palestinian medicinal plants for potential anti-inflammatory and cytotoxic activity. , 2007, Journal of ethnopharmacology.

[2]  Xianglin Shi,et al.  Apigenin Induces Apoptosis in Human Leukemia Cells and Exhibits Anti-Leukemic Activity In Vivo , 2011, Molecular Cancer Therapeutics.

[3]  Manuel T. Silva.  Secondary necrosis: The natural outcome of the complete apoptotic program , 2010, FEBS letters.

[4]  Cytotoxicity of Selected Medicinal and Nonmedicinal Plant Extracts to Microbial and Cervical Cancer Cells , 2012, Journal of biomedicine & biotechnology.

[5]  Y. Lou,et al.  Inhibition of skin tumorigenesis by rosemary and its constituents carnosol and ursolic acid. , 1994, Cancer research.

[6]  G. Kızıl,et al.  DNA damage protecting activity and in vitro antioxidant potential of the methanol extract of Cyclotrichium niveum , 2009 .

[7]  M. Ark,et al.  Ouabain-induced apoptosis and Rho kinase: a novel caspase-2 cleavage site and fragment of Rock-2 , 2010, Apoptosis.

[8]  Jiye Cai,et al.  Apigenin induced MCF-7 cell apoptosis-associated reactive oxygen species. , 2014, Scanning.

[9]  Gang Chen,et al.  New cytotoxic compounds from flowers of Lawsonia inermis L. , 2014, Fitoterapia.

[10]  L. Wan,et al.  Flavones inhibit breast cancer proliferation through the Akt/FOXO3a signaling pathway , 2015, BMC Cancer.

[11]  M. Salama,et al.  Cytotoxic compounds from the leaves of Gaillardia aristata Pursh. growing in Egypt , 2011, Natural product research.

[12]  M. Inoue,et al.  Studies on constituents with cytotoxic and cytostatic activity of two Turkish medicinal plants Phlomis armeniaca and Scutellaria salviifolia. , 1995, Biological & pharmaceutical bulletin.

[13]  Xiao Xu,et al.  The xCELLigence system for real-time and label-free monitoring of cell viability. , 2011, Methods in molecular biology.

[14]  S. Sauer,et al.  Melissa officinalis extract induces apoptosis and inhibits proliferation in colon cancer cells through formation of reactive oxygen species. , 2015, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[15]  M. Ark,et al.  Ouabain induces Rho-dependent rock activation and membrane blebbing in cultured endothelial cells , 2015, Molecular Biology.

[16]  Mechanistic Studies of Antiproliferative Effects of Salvia triloba and Salvia dominica (Lamiaceae) on Breast Cancer Cell Lines (MCF7 and T47D) , 2014, Zeitschrift fur Naturforschung. C, Journal of biosciences.

[17]  Hung-Tse Huang,et al.  Triterpene Acids from Euscaphis japonica and Assessment of Their Cytotoxic and Anti-NO Activities , 2012, Planta Medica.

[18]  A. Ulubelen,et al.  Flavanones from Cyclotrichium niveum , 1989 .

[19]  K. Başer,et al.  The Essential Oil of Cyclotrichium niveum (Boiss.) Manden. et Scheng. , 1994 .

[20]  Y. Ito,et al.  Search for possible antitumor promoters by inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced Epstein-Barr virus activation; ursolic acid and oleanolic acid from an anti-inflammatory Chinese medicinal plant, Glechoma hederaceae L. , 1986, Cancer letters.

[21]  K. Pennington,et al.  Mode of action of pulegone on the urinary bladder of F344 rats. , 2012, Toxicological sciences : an official journal of the Society of Toxicology.

[22]  B. Tepe,et al.  Determination of in vitro antioxidative and antimicrobial properties and total phenolic contents of Ziziphora clinopodioides, Cyclotrichium niveum, and Mentha longifolia ssp. typhoides var. typhoides. , 2009, Journal of medicinal food.

[23]  T. Uchiyama,et al.  Cytotoxic activity of Perilla frutescens var. japonica leaf extract is due to high concentrations of oleanolic and ursolic acids , 2006, Journal of Natural Medicines.

[24]  G. D. Rowley,et al.  Flora of Turkey and the East Aegean Islands. , 1966 .

[25]  I. Orhan,et al.  Acetylcholinesterase inhibitory and antioxidant properties of Cyclotrichium niveum, Thymus praecox subsp. caucasicus var. caucasicus, Echinacea purpurea and E. pallida. , 2009, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[26]  A. Gökbulut.  Validated Rp-Hplc Method For Quantification of Phenolic Compounds In Methanol Extracts of Aerial Parts and Roots of Thymus Sipyleus and Evaluation of Antioxidant Potential , 2015 .

[27]  류지형,et al.  정유(Essential Oil)와 그 응용 , 2008 .

[28]  I. Gulcin,et al.  Antioxidant, Antimicrobial, Antifungal, and Antiradical Activities of Cyclotrichium Niveum (BOISS.) Manden and Scheng , 2008 .

[29]  D. Newman,et al.  Plants as a source of anti-cancer agents. , 2005, Journal of ethnopharmacology.

[30]  Ke-Chun Liu,et al.  Cytotoxic prenylated bibenzyls and flavonoids from Macaranga kurzii. , 2014, Fitoterapia.

[31]  N. Vural,et al.  Scavenging effect and antispasmodic activity of the essential oil of Cyclotrichium niveum. , 2007, Fitoterapia.