Antineoplastic effects of deoxyelephantopin, a sesquiterpene lactone from Elephantopus scaber, on lung adenocarcinoma (A549) cells / 中西医结合学报

<p><b>OBJECTIVE</b>Deoxyelephantopin, a sesquiterpene lactone from Elephantopus scaber, showed inhibition of the growth of various tumor cells in vitro. In the present study, we investigated the cytotoxicity and apoptosis-inducing capacity of deoxyelephantopin on lung adenocarcinoma (A549) cells.</p><p><b>METHODS</b>The cytotoxic effect of deoxyelephantopin on A549 cells and normal lymphocytes was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and 50% inhibitory concentration (IC50) value was determined. The self-renewal and proliferating potential of A549 cells after treatment with deoxyelephantopin were examined by colony formation assay. Cellular morphology of deoxyelephantopin-treated cells was observed using phase-contrast microscopy. The induction of apoptosis was evaluated using acridine orange and ethidium bromide staining, Hoechst 33342 staining, terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end-labeling (TUNEL) assay, DNA fragmentation analysis and Annexin V-fluorescein isothiocyanate staining by flow cytometry. Activation of caspases was detected using fluorogenic substrate specific to caspases 2, 3, 8 and 9 and flow cytometric analysis. The total cellular DNA content and expression of cleaved poly (ADP-ribose) polymerase was also analyzed.</p><p><b>RESULTS</b>Deoxyelephantopin exhibited cytotoxicity to A549 cells (IC50 = 12.287 μg/mL), however, there was no toxicity towards normal human lymphocytes. Deoxyelephantopin suppressed the colony-forming ability of A549 cells in a dose-dependent manner. Acridine orange, ethidium bromide and Hoechst 33342 staining showed cell shrinkage, chromosomal condensation and nuclear fragmentation, indicating induction of apoptosis. Deoxyelephantopin increased apoptosis of A549 cells, as evidenced by more TUNEL-positive cells. DNA fragmentation and Annexin V staining revealed late-stage apoptotic cell population. Deoxyelephantopin inhibited A549 cell growth by cell cycle arrest at G2/M phase and induced apoptosis through both extrinsic and intrinsic pathways.</p><p><b>CONCLUSION</b>These results suggest that deoxyelephantopin has great potential as a new chemotherapeutic agent to be developed further for the treatment of lung cancer.</p>

Markers of hepatitis B virus infection in asymptomatic drug abusers in Malaysia.

Sera from 200 Malaysian male drug abusers were tested for markers of Hepatitis B virus (HBV) infection, viz. HBsAg, HBeAg, anti-HBs and anti-HBc using commercially available enzyme immunoassay (EIA) kits supplied by Abbot Laboratories, Chicago. Of these, 103 (51.5%) were positive for at least one HBV marker, 11 (5.5%) were positive for HBsAg; 4 (2%) for HBeAg, 74 (37%) for anti-HBs and 85 (42.5%) for anti-HBc. The HBsAg carrier rate was roughly the same as the carrier rate in the general population of Malaysia. The majority of drug abusers (95%) have had subclinical, asymptomatic HBV infection. Racially the Malay drug abusers had the highest exposure rate (54.2%). The HBsAg carrier rate was highest in the Chinese drug abusers (15.3%) and lowest in the Indians (0%). The mean age for the HBsAg carriers was found to be 26 years with a mean duration of drug abuse of 72 months. The Malaysian Anti-Narcotics Task Force of the National Security Council reported in the Malay Mail (July 13, 1985) that there were about 106,000 identified drug abusers in Malaysia and that 63% of these were in the 20-29 age groups. It appears from our study that this age group also coincides with the period of high HBsAg carrier rate. Age wise, those less than 21 years old had the highest HBsAg (11%) and HBeAg (5.6%) prevalence rates indicating high infectivity. After the age of 30 years, nearly 50% of the drug abusers appear to be immune with the HBe prevalence of 0%.(ABSTRACT TRUNCATED AT 250 WORDS)