REVIEW ARTICLESBetulinic acid, a natural compound with potent anticancer effectsMullauer, Franziska B.a; Kessler, Jan H.a b; Medema, Jan PaulaAuthor Information aLaboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam bDepartment of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands Correspondence to Jan Paul Medema, Laboratory for Experimental Oncology and Radiobiology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands Tel: +31 20 5667777; fax +31 20 6977192; e-mail: [email protected] Received 22 October 2009 Revised form accepted 18 November 2009 Anti-Cancer Drugs: March 2010 - Volume 21 - Issue 3 - p 215-227 doi: 10.1097/CAD.0b013e3283357c62 Buy Metrics Abstract New therapies using novel mechanisms to induce tumor cell death are needed with plants playing a crucial role as a source for potential anticancer compounds. One highly promising class of natural compounds are the triterpenoids with betulinic acid (BetA) as the most prominent representative. In-vitro studies have identified this agent as potently effective against a wide variety of cancer cells, also those derived from therapy-resistant and refractory tumors, whereas it has been found to be relatively nontoxic for healthy cells. In-vivo preclinically applied BetA showed some remarkable anticancer effects and a complete absence of systemic toxicity in rodents. BetA also cooperated with other therapies to induce tumor cell death and several potent derivatives have been discovered. Its antitumor activity has been related to its direct effects on mitochondria where it induces Bax/Bak-independent cytochrome-c release. © 2010 Lippincott Williams & Wilkins, Inc.