Sabtu, 6 Julai 2013

Betulinic Acid for cancer treatment and prevention

Betulinic Acid for cancer treatment and prevention.

University Children's Hospital, Ulm, Germany.

International Journal of Molecular Sciences (impact factor: 1.39). 07/2008; 9(6):1096-107. DOI:10.3390/ijms9061096

Source: PubMed

ABSTRACT Betulinic acid is a natural product with a range of biological effects, for example potent antitumor activity. This anticancer property is linked to its ability to induce apoptotic cell death in cancer cells by triggering the mitochondrial pathway of apoptosis. In contrast to the cytotoxicity of betulinic acid against a variety of cancer types, normal cells and tissue are relatively resistant to betulinic acid, pointing to a therapeutic window. Compounds that exert a direct action on mitochondria present promising experimental cancer therapeutics, since they may trigger cell death under circumstances in which standard chemotherapeutics fail. Thus, mitochondrion-targeted agents such as betulinic acid hold great promise as a novel therapeutic strategy in the treatment of human cancers.


Betulinic acid, a natural compound with potent anticancer effects

Mullauer, Franziska B.a; Kessler, Jan H.a b; Medema, Jan Paula


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.

Betulinic acid exerts immunoregulation and anti-tumor effect on cervical carcinoma (U14) tumor-bearing mice


Phytochemicals used in cancer therapy and prevention are an important source. Betulinic acid (BetA), a lupine-type pentacyclic triterpenoid saponin from plants, has shown anti-tumor activity in some cell lines in previous studies. In this paper, its anti-tumor effect and the possible mechanisms were investigated in U14 tumor-bearing mice. The results showed that BetA (100 mg/kg and 200 mg/kg) effectively suppressed tumor growth in vivo. Compared with the control group, BetA significantly improved the levels of IL-2 and TNF- in tumor-bearing mice and increased the number of CD4+ lymphocytes subsets, as well as the ratio of CD4+/CD8+ at a dose of 200 mg/kg. Furthermore, treatment with BetA induced cells apoptosis in dose-dependent manner in tumor bearing mice, and inhibited the expression of Bcl-2 and Ki-67 protein while upregulated the expression of caspase-8 protein. The mechanisms by which BetA exerted anti-tumor effects might involve the induction of tumor cell apoptosis. This process is also related to improvement of body's immune response.






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