Dual activity of triterpenoids: apoptotic versus antidifferentiation effects.
Triterpenoids are natural, biologically active compounds extracted from many plants. They possess antiinflammatory, anticancer, and antioxidant properties. In the report presented, antiproliferative effects and leukemia cell growth and apoptosis modulating activities of ursolic acid (UA) and oleanolic acid (OA) were investigated. Both triterpenoids are inhibitors of leukemia cell growth and inductors of apoptosis. However, when applied in combination with anthracycline antitumor antibiotic doxorubicin (Dox), UA and OA diversely modulate therapeutic efficacy of Dox, due to different antioxidant activities. Compare to OA showing synergism/additive effect with Dox, UA (stronger antioxidant) acts antagonistically and reduces leukemia cell growth inhibiting and differentiation effects induced by Dox. In conclusion, these findings suggest that although triterpenoids UA and OA can induce apoptosis, their antioxidant activities can interfere with the therapeutic effect of antitumor antibiotic Dox which mechanism of action is attributed to the production of reactive oxygen species.
Cipak
Lubos
L
Cancer Research Institute, Slovak Academy of Sciences, Vlarska 7, 833-91 Bratislava, Slovakia. exoncip@savba.sk
Grausova
Lubica
L
Miadokova
Eva
E
Novotny
Ladislav
L
Rauko
Peter
P
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000473:pathology; D004317:Doxorubicin / Q000627:therapeutic use; D004338:Drug Combinations; D004347:Drug Interactions; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy / Q000473:pathology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D009828:Oleanolic Acid / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*; D000097245:Ursolic Acid
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D004317:Doxorubicin; D004338:Drug Combinations; D009828:Oleanolic Acid; D014315:Triterpenes; D000097245:Ursolic Acid