In vitro anticancer studies of α- and β-d-glucopyranose betulin anomers

Kommera, Harish; Kaluđerović, Goran N.; Bette, Martin; Kalbitz, Jutta; Fuchs, Petra; Fulda, Simone; Mier, Walter; Paschke, Ralf

doi:10.1016/j.cbi.2010.02.038

Cited by 37 publications

(29 citation statements)

References 32 publications

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“…(146) BetA did not have an effect on the division of cell cycle (136,(147)(148)(149)(150)(151)(152) in ovarian cancer cells (76), but cell cycle arrest was observed in melanoma cells, especially in the G1 phase. Several analogs, however, caused cell death by perturbations in the G2M phase (146,153) or led to an increase in the population at the S phase (149). In addition, BetA seems to accumulate in cells.…”

Section: Effects On Other Molecular Targetsmentioning

confidence: 99%

Betulinic Acid: Recent Advances in Chemical Modifications, Effective Delivery, and Molecular Mechanisms of a Promising Anticancer Therapy

et al. 2015

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An important method of drug discovery is examination of diverse life forms, including medicinal plants and natural products or bioactive compounds isolated from these sources. In cancer research, lead structures of compounds from natural sources can be used to design novel chemotherapies with enhanced biological properties. Betulinic acid (3β-hydroxy-lup-20(29)-en-28-oic acid or BetA) is a naturally occurring pentacyclic triterpene with a wide variety of biological activities, including potent antitumor properties. Non-malignant cells and normal tissues are not affected by BetA. Because BetA exerts its effects directly on the mitochondrion and triggers death of cancerous cells, it is an important alternative when certain chemotherapy drugs fail. Mitochondrion-targeted agents such as BetA hold great promise to circumvent drug resistance in human cancers. BetA is being developed by a large network of clinical trial groups with the support of the U.S. National Cancer Institute. This article discusses recent advances in research into anticancer activity of BetA, relevant modes of delivery, and the agent's therapeutic efficacy, mechanism of action, and future perspective as a pipeline anticancer drug. BetA is a potentially important agent in cancer therapeutics.

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Section: Effects On Other Molecular Targetsmentioning

confidence: 99%

Betulinic Acid: Recent Advances in Chemical Modifications, Effective Delivery, and Molecular Mechanisms of a Promising Anticancer Therapy

et al. 2015

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“…Due to its low solubility in aqueous solvents and the poor understanding of its mode of action, the therapeutic applicability is, however, limited. Therefore, several semi-synthetic derivatives of betulinic acid have been generated [6]. B10 is a new glycosylated derivative of betulinic acid with enhanced cytotoxic activity that has recently been shown to trigger cell death via the lysosomal pathway [7].…”

Section: Introductionmentioning

confidence: 99%

Hypoxia Enhances the Antiglioma Cytotoxicity of B10, a Glycosylated Derivative of Betulinic Acid

et al. 2014

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B10 is a glycosylated derivative of betulinic acid with promising activity against glioma cells. Lysosomal cell death pathways appear to be essential for its cytotoxicity. We investigated the influence of hypoxia, nutrient deprivation and current standard therapies on B10 cytotoxicity. The human glioma cell lines LN-308 and LNT-229 were exposed to B10 alone or together with irradiation, temozolomide, nutrient deprivation or hypoxia. Cell growth and viability were evaluated by crystal violet staining, clonogenicity assays, propidium iodide uptake and LDH release assays. Cell death was examined using an inhibitor of lysosomal acidification (bafilomycin A1), a cathepsin inhibitor (CA074-Me) and a short-hairpin RNA targeting cathepsin B. Hypoxia substantially enhanced B10-induced cell death. This effect was sensitive to bafilomycin A1 and thus dependent on hypoxia-induced lysosomal acidification. Cathepsin B appeared to mediate cell death because either the inhibitor CA074-Me or cathepsin B gene silencing rescued glioma cells from B10 toxicity under hypoxia. B10 is a novel antitumor agent with substantially enhanced cytotoxicity under hypoxia conferred by increased lysosomal cell death pathway activation. Given the importance of hypoxia for therapy resistance, malignant progression, and as a result of antiangiogenic therapies, B10 might be a promising strategy for hypoxic tumors like malignant glioma.

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“…The final cytotoxicity of the studied surfaces S 1-S 5 ( Table 5) have been discussed in terms of mass, using an M 50 scale (quantity of material required to inhibit normal cell growth by 50 %). [20][21][22][23] The IC 50 values of free BA under the same experimental conditions [24] have also been included in Table 5.…”

Section: Preliminary Study Of the Cytotoxicity Of All Synthesized Matmentioning

confidence: 99%

“…In vitro studies: Determination of the cytotoxicity of free BA was carried out as described in a previous report by our research group, [24] while determination of the cytotoxic activity of the novel materials was carried out using the method described below.…”

Section: Biologymentioning

confidence: 99%

Preliminary Study of the Anticancer Applications of Mesoporous Materials Functionalized with the Natural Product Betulinic Acid

et al. 2012

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Dehydrated MCM-41 (S1) was functionalized under nitrogen with 3-chloropropyltriethoxysilane (CPTS) and 3-aminopropyltriethoxysilane (APTS) by grafting in toluene at 80 °C over 48 h to give the corresponding materials S2 and S3, respectively. Subsequently, S2 and S3 were suspended in methanol and reacted in a nitrogen atmosphere with betulinic acid (BA) for 48 h at 65 °C (in the presence of the triethylamine of S2) to give the BA-functionalized materials S4 and S5. All materials studied were characterized by powder X-ray diffraction, X-ray fluorescence, nitrogen gas sorption, multinuclear MAS NMR spectroscopy, thermogravimetry, UV spectroscopy, IR, SEM, and TEM. To study the release of BA, S4 and S5 were suspended in solutions simulating various body pH conditions (pH 7.4, 5.5, and 3.0). Results of the quantification of BA release by HPLC for S4 show a pH-dependent and very slow BA release following a logarithmic tendency, while S5 behaves differently, also pH-dependent but, in this case, fast release of BA which requires only days for total release of the therapeutic compound. In addition, the cytotoxic activity of all synthesized materials against various cancer cell lines was studied. The results show the absence of an antiproliferative effect on the surfaces without BA S1-S3, while an antiproliferative effect was observed with S4 and S5 and was attributed to the release of BA in the medium.

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In vitro anticancer studies of α- and β-d-glucopyranose betulin anomers

Cited by 37 publications

References 32 publications

Betulinic Acid: Recent Advances in Chemical Modifications, Effective Delivery, and Molecular Mechanisms of a Promising Anticancer Therapy

Betulinic Acid: Recent Advances in Chemical Modifications, Effective Delivery, and Molecular Mechanisms of a Promising Anticancer Therapy

Hypoxia Enhances the Antiglioma Cytotoxicity of B10, a Glycosylated Derivative of Betulinic Acid

Preliminary Study of the Anticancer Applications of Mesoporous Materials Functionalized with the Natural Product Betulinic Acid

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