Betulinic acid decreases expression of bcl-2 and cyclin D1, inhibits proliferation, migration and induces apoptosis in cancer cells

Abstract

Betulinic acid (BA) is a pentacyclic triterpene found in many plant species, among others in the bark of white birch Betula alba. BA was reported to display a wide range of biological effects, including antiviral, antiparasitic, antibacterial and anti-inflammatory activities, and in particular to inhibit growth of cancer cells. The aim of the study was further in vitro characterization of BA anticancer activity. In this study, we demonstrated a remarkable antiproliferative effect of BA in all tested tumor cell cultures including neuroblastoma, rabdomyosarcoma-medulloblastoma, glioma, thyroid, breast, lung and colon carcinoma, leukemia and multiple myeloma, as well as in primary cultures isolated from ovarian carcinoma, cervical carcinoma and glioblastoma multiforme. Furthermore, we have shown that BA decreased cancer cell motility and induced apoptotic cell death. We also observed decrease of bcl2 and cyclin D1 genes expression, and increase of bax gene expression after betulinic acid treatment. These findings demonstrate the anticancer potential of betulinic acid and suggest that it may be taken into account as a supportive agent in the treatment of cancers with different tissue origin.

Betulinic acid inhibits autophagic flux and induces apoptosis in human multiple myeloma cells in vitro

“…Similarly, we found that caspase 3 cleavage had a role in the progression of the BA-induced apoptosis in multiple myeloma KM3 cells. The treatment of KM3 cells with various concentrations of BA (10,15, and 20 μg/mL) resulted in apoptosis rates of 15.60%±1.58%, 23.86%±2.06%, and 44.12%±3.22%, respectively, that were significantly higher than that of the control group (Figure 2). BA also contributed to caspase 3 activation in a dose-dependent manner, followed by the cleavage of PARP (Figure 4), a factor that is considered one of the major cleavage targets of caspase 3 and is involved in DNA repair in response to extracellular stress [28] .…”

“…Briefly, KM3 cells were maintained in RPMI-8226 medium until the mid-log phase. The cells were then seeded in 96-well plates with or without BA at various concentrations (5,10,15,20, and 25 μg/mL) at a density of 2×10 4 cells per well. After incubation for a set period of time, 20 μL MTT (5 mg/mL) was added, and the cells were incubated for another 3 h at 37 °C.…”

“…Betulinic acid (BA), a natural pentacyclic triterpene isolated from birch, exhibits a variety of biological activities, including anti-HIV, anti-HBV, anti-malarial [8][9][10] and potent anti-tumor properties in melanoma [11] , leukemia [12] , colon [13] , lung [14] , gliomas [15] , prostate carcinoma [16] , gastric adenocarcinoma [17] and multiple myeloma [18,19] . Various mechanisms have been reported for the extensive anticancer activity of BA, including directly triggering mitochondrial membrane permeabilization [20] , regulating Bcl-2 family proteins [21] , downregulating Hiwi expression [17] and suppressing the activation of the STAT3 pathway through the induction of the protein tyrosine phosphatase SHP-1 [19] .…”

Comparison of Cytotoxicity and the Chemical Composition in Disporopsis pernyi and its Confused Variety

“…The Cytotoxicity of EAF against MCF-7 cells might be related to Betulinic acid and Betulin [12,13]. The other fractions did not show significant activity against MCF-7 cells, so did the fractions of Polygonatum odoratum and Panax japonicus.…”

Exploitation of the Bulgarian Flora's Biodiversity as a Source of Immunomodulatory and/or Antineoplastic Agents: Current Challenges and Perspectives

“…Saponins have been long known as antineoplastic and immunostimulant agents. The discovery of the potent broadspectrum anticancer properties of betulinic acid however have further focused research interest on this class of plant secondary metabolites as possible anticancer lead compounds (1,3,4,7,8,15,16,32,34 A purifi ed mixture containing mostly saponins (PMS) from Astragalus corniculatus Bieb. was used in an in vivo tumor model to demonstrate its protective effect against myeloid Graffi tumour in hamsters, in collaboration with Dr. Reneta Toshkova (BAS).…”