Abstract: To screen and identify the anticancer components of Rabdosia serra (Maxim) Hara, the effects of the crude ethyl acetate extract of Rabdosia serra (Maxim) Hara and its purified fractions obtained by silica gel column chromatography and semi-preparative chromatography on cell viability and quinone reductase (QR/NQO1) activity were evaluated using mouse hepatoma Hepa1c1c7 cells. The purified fractions were identified by mass spectrometry (MS), 1H-nuclear magnetic renonsance (1H-NMR) and 13C-NMR. Furthermore, mouse hepatoma cells were pretreated with specific protein kinase inhibitors including phosphatidylinositol 3-kinase (PI3K) inhibitor, extracellular signal-regulated kinase (ERK) inhibitor, mitogen activated protein kinases(MAPK) p38 inhibitor, protein kinase C (PKC) inhibitor and c-Jun N-terminal kinase (JNK) inhibitor to determine the signal transduction pathways leading to the induction of QR activity. The mRNA and protein expression levels of NQO1 were measured by quantitative PCR and Western blot, respectively. Our results suggested as follows: 1) oridonin was identified as a potential anticancer component of this extract; 2) oridonin at a concentration of 0.94 μg/mL exhibited a remarkable potency in inducing QR; 3)PI3K inhibitor significantly inhibited the induction of QR activity by oridonin, while ERK inhibitor showed an opposite effect. Moreover, p38, PKC and JNK inhibitors did not significantly affect the induction effect of oridonin on QR; 4)oridonin markedly increased the expression of both mRNA and protein of NQO1. In conclusion, oridonin from Rabdosia serra (Maxim) Hara can induce QR activity in cultured Hepa1c1c7 cells by activating the PI3K signal transduction pathway and inhibiting the ERK signal transduction pathway, and it also can significantly induce the transcription and translation of NQO1. These results would provid a preliminary theoretical basis for cancer chemoprevention with Rabdosia serra (Maxim) Hara and oridonin.

Key words: Rabdosia serra (Maxim) Hara, oridonin, quinone reductase, Hepa1c1c7 cell line, signal transduction pathway