Paris Polyphylla is a traditional Chinese Medical herb that has been used in treating cancer for thousands of year. Without studies on the anticancer effects of Paris Polyphylla being initiated before, we have first studied the component of Paris Polyphylla and have spotted out a steroidal saponin, polyphyllin D. As long as the chemical structure and the improved synthesis of polyphyllin D were ascertained, both in vitro to in vivo studies were performed. It was found that treatment of MCF-7 and MDA-MB-231 cells with polyphyllin D resulted in the inhibition of viability and induction of apoptosis in a dose-dependent manner, with an IC50 of 5?M and 2.5?M, respectively, after 48 hours of incubations. Apoptosis of MCF-7 and MDA-MB-231 cells by polyphyllin D was evidenced by the occurrence of DNA fragmentation, formation of a hypodiploid peak in the cell cycle analysis, phosphatidyl-serine externalization and a late loss of membrane integrity. Mechanistically, polyphyllin D dissipates the mitochondrial membrane potential, induces a down-regulation of anti-apoptotic Bcl-2 expression and an up-regulation of pro-apoptotic Bax expression, and activates caspase-9. These results suggest that polyphyllin D elicits apoptosis through mitochondria dysfunction. In vivo study demonstrated that daily administration of polyphyllin D (2.73 mg/kg body weight) through intravenous injection for ten days in nude mice bearing MCF-7 cells effectively reduced tumor growth for 50% in terms of tumor weight and size, given no significant toxicity in heart and liver to the host. All these findings provide novel insights that polyphyllin D could serve as a candidate in breast cancer treatment.

An outbreak of severe acute respiratory syndrome (SARS) occurred in China and the first case emerged in mid-November 2002. The aetiological agent of this disease was found to be a previously unknown coronavirus, SARS-associated coronavirus (SARS-CoV). The detailed pathology of SARS-CoV infection and the host response to the viral infection are still not known. The 3a gene encodes a non-structural viral protein, which is predicted to be a transmembrane protein. In this study, it was shown that the 3a protein was expressed in the lungs and intestinal tissues of SARS patients and that the protein localized to the endoplasmic reticulum in 3a-transfected monkey kidney Vero E6 cells. In vitro experiments of chromatin condensation and DNA fragmentation suggested that the 3a protein may trigger apoptosis. These data showed that overexpression of a single SARS-CoV protein can induce apoptosis in vitro.

Background: Imperatorin (IM) is a furanocoumarin isolated from the root of Angelica dahurica, which is reported to have anticonvulsant and anticancer effects. In this study, the antiproliferative effect of IM on 9 human cancer cell lines was examined, and human hepatoma HepG2 cells were chosen as the target for preferential killing by IM. Particularly, the mechanism of IM-induced apoptosis and in vivo animal effects were also studied. Methods: Cell viability was measured using MTT assay, and apoptosis was detected by Hoechst staining, annexin V-PI staining, and DNA laddering assay. Mitochondrial membrane potential was detected by JC-1 staining. Western blot analysis was employed to detect the expression of apoptosis-related proteins. In addition, the in vivo anticancer effect of IM was examined in nude mice bearing HepG2 cells. Results: IM inhibited the proliferation of HepG2 cells through apoptosis induction in a time- and dose-dependent manner by observation of the nuclear morphology, DNA fragmentation, phosphatidylserine externalization, loss of mitochondrial membrane potential, release of cytochrome c into cytosol, and activation of caspase-3, caspase-8, caspase-9, and poly(ADP-ribose) polymerase cleavage. As cell death could partly be prevented by the caspase-8 or caspase-9 inhibitor and was evidenced by the results of Western blot analysis, our results also suggest that IM-induced apoptosis is mediated through both death receptor and mitochondrial pathways. In the animal model, IM was found to effectively suppress tumor growth by 31.93 and 63.18% at dosages of 50 and 100 mg/kg, respectively, after treatment for 14 days. No significant weight loss or toxicity to the hosts was found. Conclusions: IM can function as a cancer suppressor by inducing apoptosis in HepG2 cells through both death-receptor- and mitochondria-mediated pathways. Furthermore, the in vivo antitumor activities of IM are significant with negligible weight loss and damage to the host.

Scutellaria barbata has long been used as a Chinese medicine for the treatment of liver diseases such as hepatitis and hepatocellular carcinoma. In the present study, a bioassay-guided method was used to isolate the most active components from Scutellaria barbata. The anti-proliferative effects on human hepatoma HepG2 and Hep3B cells of each fraction at every stage of the purification were monitored. An active component, which is 97 % pure by high performance liquid chromatographic analysis, was isolated. Based on nuclear magnetic resonance (NMR) and mass spectrophotometric (MS) analysis, this active component was identified to be pheophorbide a (C₃₅H₃₆N₄O₅). Mechanistic studies showed that pheophorbide a induced apoptosis in Hep3B cells, a viral-induced hepatoma cell line. However, it was found to be non-toxic in normal human liver cells WRL-68. DNA fragmentation, sub-G₁ cell cycle arrest, as well as suppression of the anti-apoptotic protein Bcl-2, release of cytochrome c to the cytosol, and activation of pro-caspase 3 and pro-caspase 9 were observed when Hep3B cells were treated with 40 μg/mL (i. e., 67.5 μM) pheophorbide a for 48 hours. In conclusion, this is the first report describing the isolation of pheophorbide a from Scutellaria barbata using a bioassay-guided isolation method. The anti-proliferative activity and possible mechanisms of action of pheophorbide a on hepatoma Hep3B cells are also discussed.