Betulin Elicits Anti‐Cancer Effects in Tumour Primary Cultures and Cell Lines In Vitro

Abstract

Betulin is a pentacyclic triterpene found in many plant species, among others, in white birch bark. The aim of the study was in vitro characterization of the anticancer activity of betulin in a range of human tumour cell lines (neuroblastoma, rhabdomyosarcoma-medulloblastoma, glioma, thyroid, breast, lung and colon carcinoma, leukaemia and multiple myeloma), and in primary tumour cultures isolated from patients (ovarian carcinoma, cervical carcinoma and glioblastoma multiforme).In this study, we demonstrated a remarkable anti-proliferative effect of betulin in all tested tumour cell cultures. Neuroblastoma (SK-N-AS) and colon carcinoma (HT-29) were the most sensitive to the anti-proliferative effect of betulin. Furthermore, betulin altered tumour cells morphology, decreased their motility and induced apoptotic cell death. These findings demonstrate the anti-cancer potential of betulin and suggest that they may be applied as an adjunctive measure in cancer treatment.

Evidence that RASSF1C Stimulation of Lung Cancer Cell Proliferation Depends on IGFBP-5 and PIWIL1 Expression Levels

“…This is consistent with our previous findings in breast cancer cells [13]. In addition, RASSF1C over-expression also reduces the effects of the anti-cancer agent, betulinic acid, which is known to decrease lung cancer cell proliferation [22]. This further supports the growth promoting and apoptosis attenuating actions of RASSF1C.…”

“…It does this, at least in part, by down-regulating PIWILI, cyclin B1, cyclin D1, bcl2 and up-regulating bax gene expression in several types of cancer cells, including A549 [22], [26], [27]. We have previously demonstrated that RASSF1C over-expression up-regulates PIWIL1 gene expression and thus we wanted to determine if RASSF1C over-expression would reduce the anti-proliferative effects of BA on lung cancer cells.…”

“…BA has previously been shown to reduce human cancer cell proliferation and down-regulate piwil1 mRNA expression in gastric adenocarcinoma cells [22], [26]. We assessed the effects of BA on piwil1 gene expression in lung cancer cells using RT-PCR and Western blot analysis.…”

“…In order to do this, we designed experiments to determine the effects of RASSF1C on lung cancer cell proliferation, migration and tumor sphere formation. Because the anti-cancer agent, betulinic acid (BA), has been shown to down-regulate PIWIL1 gene expression [22], we studied the effects of BA and RASSF1C/IGFBP-5 interaction on PIWIL1 gene expression and β-catenin protein levels. We found that RASSF1C promotes cancer cell migration and tumor sphere formation, and reduces the inhibition of proliferation by BA.…”

Betulinic Acid in Complex with a Gamma-Cyclodextrin Derivative Decreases Proliferation and in Vivo Tumor Development of Non-Metastatic and Metastatic B164A5 Cells

“…Additionally, betulin, which differs from BA by a single functional group, was also described for its property to induce an antiproliferative effect on other human cell lines, such as hepatoma (HepG2) cells and lung adenocarcinoma (A549) cells [17]. Anticancer effects were also reported for neuroblastoma (SK-N-AS) cells and colon carcinoma (HT-29) cells [18]. However, as reported so far in several significant papers, BA remains the triterpene of choice for anticancer activity on both human and murine melanoma models.…”