Tumor cell specific toxicity of Inula helenium extracts.
The aim of the research program was to identify botanical extracts with antineoplastic activity. In this respect extracts prepared from Inula helenium roots showed a remarkable activity. As evidenced by the MTT assay, the Inula helenium extract revealed a highly selective toxicity toward four different tumor cell lines (HT-29, MCF-7, Capan-2 and G1), but a much lower toxicity against healthy human peripheral blood lymphocytes (PBLs) from two donors. The extract-induced death of tumor cells was studied extensively by electron microscopy. There was a remarkable similarity of morphological alterations observed in the four cell lines: patchy chromatin condensations, cytoplasmic vesiculation, swelling and rupture of mitochondria. The morphology of cellular breakdown bore more resemblance to necrotic than to apoptotic cell death, which was supported by the failure to mark early apoptotic events by Annexin V. It has been pointed out recently that compounds inducing cell death with necrotic-like morphology could be very beneficial in cases where cancerous cells have gained resistance to apoptosis. In this context, the remarkable difference in cytotoxicity exerted by the Inula helenium extract, which was over 100-times higher in the tumor cell lines than in the PBLs, makes the extract an excellent candidate for further anticancerous investigations, especially since the Inula helenium extract was not mutagenic in the Ames test.
Dorn
David C
DC
Laboratory of Developmental Hematopoiesis, Cell Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Alexenizer
Maja
M
Hengstler
Jan G
JG
Dorn
August
A
D017304:Annexin A5 / Q000032:analysis; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D038143:Inula / Q000737:chemistry* / Q000633:toxicity*; D007928:Lethal Dose 50; D008214:Lymphocytes / Q000187:drug effects*; D009152:Mutagenicity Tests; D010936:Plant Extracts / Q000633:toxicity*; D018517:Plant Roots / Q000737:chemistry / Q000633:toxicity; D023382:Toxicity Tests, Acute
D017304:Annexin A5; D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts