Arehzoo Zaker - Department of Biology, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, Iran
Javad Asili - Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Parvaneh Abrishamchi - Department of Biology, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, Iran
Zahra Tayarani-Najaran - Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Seyed Hadi Mousavi - Medical Toxicology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Objective(s):Perovskia abrotanoides Kar., from family Lamiaceae, is a little known medicinal plant growing in various regions of Iran. In the present study, cryptotanshinone (CT), tanshinone ۲A (Tan۲A), and hydroxycryptotanshinone (HCT) were isolated and purified from the roots of P. abrotanoides. In addition, cytotoxic and apoptotic effects of total root extract (TE) and three purified tanshinones were investigated in human cervical carcinoma (HeLa) and human breast cancer (MCF-۷) cell lines.  Materials and Methods: Alamar Blue® assay was used to determine cell viability. Cell apoptotic rate was detected using propidium iodide staining of DNA fragmentation by flow cytometry (sub-G۱ peak). The PARP cleavage, as the sign of apoptosis, was investigated by Western blotting. Results: The results revealed that CT, Tan۲A, HCT, and TE exhibited significant cytotoxicity in cancer cell lines. All of these compounds caused apoptosis in treated cells and induced sub-G۱ peak in the related flow cytometry histograms. HCT was found to have the highest anti-proliferative activity on cancer cells. Western blotting analysis showed cleavage of PARP protein in MCF-۷ cells treated with purified tanshinones and TE after ۴۸ hr contact with cells. Conclusion: The findings suggest that root extract of P. abrotanoides and purified tanshinones especially Tan۲A and HCT have cytotoxic and apoptotic effects against cancer cell lines. So, they may serve as potential cytotoxic agents for future investigations.

Apoptosis, Cytotoxicity, HeLa, MCF-۷, Perovskia abrotanoides, Root extract, Tanshinone