Identification of potent anticancer activity in Ximenia americana aqueous extracts used by African traditional medicine.
The antineoplastic activity of a plant powder used in African traditional medicine for treating cancer was investigated by analyzing the activity of various extracts in vitro. The most active, aqueous extract was subsequently subjected to a detailed investigation in a panel of 17 tumor cell lines, showing an average IC50 of 49 mg raw powder/ml medium. The sensitivity of the cell lines varied by two orders of magnitude, from 1.7 mg/ml in MCF7 breast cancer cells to 170 mg/ml in AR230 chronic-myeloid leukemia cells. Immortalized, non-tumorigenic cell lines showed a marginal sensitivity. In addition, kinetic and recovery experiments performed in MCF7 and U87-MG cells and a comparison with the antineoplastic activity of miltefosine, gemcitabine, and cisplatinum in MCF7, U87-MG, HEp2, and SAOS2 cells revealed no obvious similarity between the sensitivity profiles of the extract and the three standard agents, suggesting a different mechanism of cytotoxicity. The in vivo antitumor activity was determined in the CC531 colorectal cancer rat model. Significant anticancer activity was found following administration of equitoxic doses of 100 (perorally) and 5 (intraperitoneally) mg raw powder/kg, indicating a 95% reduced activity following intestinal absorption. By sequencing the mitochondrial gene for the large subunit of the ribulose bis-phosphate carboxylase (rbcL) in DNA from the plant material, the source plant was identified as Ximenia americana. A physicochemical characterization showed that the active antineoplastic component(s) of the plant material are proteins with galactose affinity. Moreover, by mass spectrometry, one of these proteins was shown to contain a stretch of 11 amino acids identical to a tryptic peptide from the ribosome-inactivating protein ricin.
Voss
Cristina
C
Unit of Toxicology and Chemotherapy, Deutsches Krebsforschungszentrum Heidelberg, E100, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Eyol
Ergül
E
Berger
Martin R
MR
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy*; D016488:Medicine, African Traditional; D009368:Neoplasm Transplantation; D031656:Olacaceae / Q000737:chemistry*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D014867:Water; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D014867:Water