Apoptotic and breast tumor inhibition effects of Ferulago angulata and Tanacetum polycephalum (L.) Schultz-bip / Hamed Karimian

Hamed , Karimian (2017) Apoptotic and breast tumor inhibition effects of Ferulago angulata and Tanacetum polycephalum (L.) Schultz-bip / Hamed Karimian. PhD thesis, University of Malaya.

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Abstract

In the present study, fifteen plants were screened for their anticancer activity against ten different cancer cell lines. Amongst these, in vitro and in vivo study of Ferulago angulata and Tanacetum polycephalum (L.) Schultz-Bip showed significant activity against MCF-7 breast cancer cells. Both, F. angulata and T. polycephalum leaves were extracted using organic solvents in the order of increasing polarity. The result of MTT assay indicated significant cytotoxic activity of hexane extract of F. angulata (FALHE) and T. polycephalum (TPHE) leaves against MCF-7 cells. FALHE and TPHE inhibit cell proliferation and promote intrinsic pathway of apoptosis in MCF-7 cells, followed by arrest in G1 cell cycle proliferation. The in vivo chemopreventive effect of FALHE and TPHE treatments in mammary gland tumor model in the rats (LA7) was seen through the inhibition of tumor markers PCNA and Ki67 and encourage apoptotic processes in tumor cells by increasing in expression of Bax, p53 and caspase-3. Phytochemical isolation of the secondary metabolites of the plants, revealed the polycerasoidin and 8β- hydroxyl- 4β, 15- dihydrozaluzanin C (HDZC) as a bioactive constituent of FALHE and TPHE, respectively. Early and late apoptosis’s markers were detected in MCF-7 cells upon treatment with polycerasoidin and HDZC; these were attributed to the intrinsic mitochondrial pathway based on the up-regulation of Bax and the down-regulation of Bcl-2 proteins. Cell cycle arrest occurred upon the treatment of MCF-7 cells with polycerasoidin and HDZC, which resulted in up-regulation of p21 and p27 at the mRNA and protein levels. Taken together, the results presented in this study demonstrated that, the T. Polycephalum and Ferulago angulata inhibit the proliferation of breast cancer cells, apoptosis and cell cycle arrest in vitro and in vivo.

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