The Experimental Study Of Antitumorigenic Effect Of Parthenolide

Parthenolide is a sesquiterpene lactone and extracted from feverfew , molecular formula:C₁₅H₂₀O₃, molecular weight:248.3. It is commonly used to therapy skin infection, rheumatic disorder, migraine in west countries. It is well known that many natural products inhibit tumor cells proliferation by inducing apoptosis and blocking cell cycle. Recent years, many biological activities of parthenolide have been found, and it can inhibit various cancers. Therefore, it is reasonable that parthenolide may inhibit tumor growth by the induction of apoptosis.Objective To observe anti-tumour effect of parthenolide on BEL-7402 cell line and explore its molecular mechanism to provide experimental evidence for further clinical application of parthenolide.Methods Human hepatocellular carcinoma BEL-7402 cell line was cultured in vitro and treated by different concentrations of parthenolide. The cell without adding parthenolide was used as control. The inhibition of cell growth induced by various concentrations of parthenolide was analyzed by MTT assay. The morphologic changes of apoptosis were observed under invert microscope and Giemsa staining. DNA ladder was examined by DNA agarose gel eletronphores. The expression levels of P53, NF-κB and PCNA albumen were measured with immunohistochemistry.Results MTT assay showed that the growth of BEL-7402 was significantly inhibited in a marked dose-dependent manner. Apoptosis with nuclear chromatin condensation, fragmentation and cell shrinkage was found by invert microscope; Giemsa staining showed the formation of apoptotic bodies. The cell exhibited changes of apoptosis in the characteristic of electrophores. Parthenolide treated BEL-7402 cells in viro after 48h, immunohistochemical results showed that NF-κB activity was inhibited, the expression of P53 was increased and the expression of PCNA was decreased by the dose-response relationship.Conclusion Parthenolide can inhibit the growth of human hepatocellular carcinoma BEL-7402 cell line and induce the cell apoptosis which may be related to mechanism of inhibition of BEL-7402 cell line. Their mechanism may be due to advancing the expression of P53 and inhibiting the expression of PCNA. In addition, parthenolide can rapidly inhibit activition and translocation of NF-κB which may be also one of signaling factor for inducing apoptosis.