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Sabtu, 6 Julai 2013
Betulinic Acid for cancer treatment and prevention
Acid for cancer treatment and prevention.
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
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.