The mechanism of the cytotoxic effect of Panax notoginseng extracts on prostate cancer cells.

INTRODUCTION: Panax notoginseng (Burkill) F.H. commonly referred to as Sanqi, is a Chinese herb that has long been used to treat various conditions including blood disorders and cardiovascular diseases. While Panax notoginseng has been used as an anti-cancer medicinal herb in recent years, how it achieves this therapeutic effect has not been thoroughly elucidated. The purpose of this study was to reveal more about the mechanism of the cytotoxic effect of Panax notoginseng on prostate cancer (PCa) cells. METHODS: Ethanol extract of Panax notoginseng root was authenticated using high-performance liquid chromatography (HPLC). The cytotoxic activity of this herb against PCa cells was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). RESULTS: The assessment of cellular metabolic activity demonstrated that Panax notoginseng reduces the viability of LNCaP and 22Rv1 cells in a dose-dependent manner. Annexin-V binding flow cytometry assay showed that Panax notoginseng induces apoptosis in PCa cells. Cell cycle analysis by quantification of DNA content using flow cytometry showed that Panax notoginseng arrests the cell cycle at the G2/M phase in both LNCaP and 22Rv1 cells. Moreover, ELISA demonstrated that Panax notoginseng-treated PCa cells secrete significantly less tumor-promoting cytokine interleukin-4 (IL-4) to the supernatant compared with controls. CONCLUSIONS: These results provide evidence for the cytotoxic effects of Panax notoginseng on PCa cell lines. This botanical is a promising candidate for the complementary and integrative medicine treatment of PCa and further studies are indicated to determine the anti-cancer mechanism of Panax notoginseng.

Direct, DNA pol-gamma-independent effects of nucleoside reverse transcriptase inhibitors on mitochondrial bioenergetics.

Nucleoside reverse transcriptase inhibitor (NRTI)-induced cardiomyopathy has been suggested to reflect mitochondrial targets of drug toxicity. The prevailing hypothesis is that, through structural mimicry, the NRTIs are mistaken as substrates for DNA polymerase and incorporated into replicating DNA, where they cause truncation of the elongating strand. Although there exist five forms of nuclear DNA polymerase, mitochondria possess solely DNA polymerase-gamma (pol-gamma), which is a preferred target for most NRTIs. Consequently, mitochondria are particularly susceptible to inhibition of DNA replication by the NRTIs, which is consistent with the phenotype of mitochondrial depletion and metabolic failure in affected patients. However, the DNA pol-gamma hypothesis by itself fails to explain the entire array of metabolic deficiencies associated with NRTI-induced disorders. In this article, we review the published literature regarding the direct effects of NRTIs on various mitochondrial targets and suggest the possibility that the initiating event in NRTI-induced cardiomyopathy is a direct mitochondrial toxicity rather than inhibition of mitochondrial DNA pol-gamma. The goal of this review is to encourage a discussion of the cause of NRTI-induced mitochondrial cardiomyopathy to include a fresh consideration of all possible targets and integrating pathways that are involved in establishing mitochondrial bioenergetic fidelity and metabolic capacity in the affected myocardium.