Betulinic acid delivered in liposomes reduces growth of human lung and colon cancers in mice without causing systemic toxicity.
Betulinic acid (BetA) is a plant-derived pentacyclic triterpenoid with potent anticancer capacity that targets the mitochondrial pathway of apoptosis. BetA has a broad efficacy in vitro against prevalent cancer types, including lung, colorectal, prostate, cervix and breast cancer, melanomas, neuroblastomas, and leukemias. The cytotoxic effects of the compound against healthy cells are minimal, rendering BetA a promising potential anticancer drug. However, because of the weak hydrosolubility of BetA, it has been difficult to study its efficacy in vivo and a pharmaceutical formulation is not yet available. We report the development of a liposome formulation of BetA and show its successful application in mice. Large liposomes, assembled without cholesterol to reduce their rigidity, efficiently incorporated BetA. Nude mice xenografted with human colon and lung cancer tumors were treated intravenously with the BetA-containing liposomes. Tumor growth was reduced to more than 50% compared with the control treatment, leading to an enhanced survival of the mice. Oral administration of the liposomal formulation of BetA also slowed tumor growth. Any signs of systemic toxicity caused by BetA treatment were absent. Thus, liposomes are an efficient formulation vehicle for BetA, enabling its preclinical development as a nontoxic compound for the treatment of cancers.
Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Experimental and Molecular Medicine, Academic Medical Center (AMC), Amsterdam, The Netherlands.
Franziska B
FB
Mullauer
Louis
L
van Bloois
Joost B
JB
Daalhuisen
Marieke S
MS
Ten Brink
Gert
G
Storm
Jan Paul
JP
Medema
Raymond M
RM
Schiffelers
Jan H
JH
Kessler
D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016503:Drug Delivery Systems; D004355:Drug Stability; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008081:Liposomes / Q000737:chemistry; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects; D053978:Pentacyclic Triterpenes; D012235:Rhodamines; D014315:Triterpenes / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D000094062:Betulinic Acid
D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D053978:Pentacyclic Triterpenes; D012235:Rhodamines; D014315:Triterpenes; D000094062:Betulinic Acid