Cytotoxic Activities of Major Diterpenoid Constituents of Andrographis paniculata in a Panel of Human Tumor Cell Lines

摘要

The cytotoxic activities of several diterpenoid constituents of the medicinal plant, "hempedu bumi," or Andrographis paniculata Nees (Acanthaceae), were evaluated. The seven diterpenoid compounds used were andrographolide, 14-deoxyandrographolide, andrographiside, deoxyandrographiside, 14-deoxy-12-methoxyandrographolide, neoandrographolide, and 14-deoxy-ll, 12-didehydroandrographolide. The activities of these compounds were evaluated with various human tumor cell lines such as Caov-3 (human ovarian carcinoma cell line), T-47D (human breast carcinoma cell line), Hs-578T (human breast carcinoma cell line), Hep G2 (human hepatocarcinoma cell line), and NCI-H23 (human lung adenocarcinoma cell line). Cell survival was measured using the MTS assay after 72 h of incubation. Andrographolide, neoandrographolide, andrographiside, deoxyandrographiside, and 14-deoxy-12-methoxyandrographolide appeared to be noncytotoxic against all the cell lines. Only 14-deoxyandrographolide and 14-deoxy-ll, 12-didehydroandrographolide exhibited cytotoxic activities (based on EC_(50) values), but this was limited to the T-47D cell line (EC_(50) values of 2.8mug/ml and 1.5 mug/ml, respectively). As one of the principle diterpenoids of Andrographis paniculata, 14-deoxy-ll, 12-didehydroandrographolide appeared to be the most potent when compared with the rest of the compounds examined. The effects of 14-deoxy-ll, 12-didehydroandrographolide on T-47D cells were further confirmed to be nonapoptotic, non-necrotic, but programmed in nature, as demonstrated using a DNA fragmentation detection assay, Trypan blue exclusion assay, and annexin V-propidium iodide staining.