Romanian Society of Pharmaceutical Sciences
 

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CYTOTOXIC AND APOPTOGENIC PROPERTIES OF DRACOCEPHALUM KOTSCHYI AERIAL PART DIFFERENT FRACTIONS ON CALU-6 AND MEHR-80 LUNG CANCER CELL LINES

TOOBA AHMADZADEH SANI 1#, ELHAM MOHAMMADPOUR 1,2#, AMENEH MOHAMMADI 1#, TOKTAM MEMARIANI 2#, MEHRAN VATANCHIAN YAZDI 4#, RAMIN REZAEE 5#, DANIELA CALINA 6#, ANCA OANA DOCEA 7#, MARINA GOUMENOU 8,9#, LEILA ETEMAD 10#, SHABNAM SHAHSAVAND 11#*

1.Research Center of Natural Products and Medicinal Plants, North Khorasan University of Medical Sciences, Bojnurd, Iran
2.Department of Biochemistry, Payame Noor University, Mashhad, Iran
3.Central Research Laboratory, North Khorasan University of Medical Sciences, Bojnurd, Iran
4.Department of Anatomy, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
5.Department of Physiology and Pharmacology, School of Medicine, North Khrosan University of Medical Sciences, Bojnurd, Iran
6.Department of Clinical Pharmacology, University of Medicine and Pharmacy, Faculty of Pharmacy, Craiova, 200349, Romania
7.Department of Toxicology, University of Medicine and Pharmacy, Faculty of Pharmacy, Craiova, 200349, Romania
8.Laboratory of Toxicology, Medical School, University of Crete, Heraklion, Greece
9.Pesticides Department, European Food Safety Authority, Parma, Italy
10.Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
11.Department of Physiology and Pharmacology, School of Medicine, North Khorasan University of Medical Sciences, P.O. Box 94176 94735, Bojnurd, Iran

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Dracocephalum kotschyi is one of the Iranian medicinal plants. The aim of this study was to assess in vitro, the cytotoxic, antiproliferative and apoptotic effects of this plant against lung cancer cell lines (Calu-6 and Mehr-80). Cell viability was quantified by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay following 24 and 48 h exposure to (12.5 ‑ 200 μg/mL) of plant methanolic extract, dichloromethane (CH2Cl2), ethyl acetate (EtOAc), hexane, water fractions and the essential oil (EO). Further fractionation of primary total methanolic extract revealed luteolin (F10) as the major component. The chemical constituents of EO were identified using gas chromatography linked mass spectrometry (GC MS) analysis. The percentage of apoptotic cells was determined using propidium iodide (PI) staining of DNA fragments by flow cytometry (sub G1 peak). Morphological changes in cells were identified. The most effective fractions were CH2Cl2 fraction, EO and luteolin (F10) (IC50; 79.1 ± 5.36, 62.2 ± 6.94 and 56.32 ± 6.58 µg/mL in Calu-6 cells and 124.2 ± 5.78, 88.13 ± 4.29 and 78.32 ± 6.59 µg/mL in Mehr-80 cell line after 48 h respectively). The DNA fragmentation assay and morphological microscopy also confirmed these data. Trans-citral (geranial) (15.65%), eucalyptol (9.32%), limonene (7.95%), beta-linalool (4.64%), neryl-acetate (3.67%) and myrcene (3.36%) were identified as the major constituents of the EO. Dracocephalum kotschyi different fractions and compounds have shown significant cytotoxic activities against Calu 6 and Mehr-80 cells.