Apoptosis as the basic mechanism of cytotoxic action of ursolic and pomolic acids in glioma cells

Pentacyclic triterpene acids: use, mode of action, Biological activity and synthesis

“…It is known that pomolic acid 7 contributes to the multiple drug resistance of cancer cells being overcome and inhibits their metastasis. [21,19] As mentioned earlier, boswellic acids are pentacyclic triterpene acids contained in the gum resin of the anti-inflammatory remedy Frankincense. The functionalities at carbons C3 and C28 of the lupane skeleton seem to be important for this activity of the triterpenes.…”

“…As mentioned above, the interest in pentacyclic triterpene acids is because of their diverse biological activity: anti-inflammatory, antimicrobial, antioxidant, antiviral, antiallergenic, antiangiogenic, hepatoprotection, antiinflammation, antitumor-promotion, anti-hyperlipidemia, antispasmodic and anti-HIV activity. [21] They are of great interest as compounds have been shown to exhibit selective cytotoxicity against malignant tumor cells. [19] In addition, natural triterpenes are popular as objects for chemical modifications in order to enhance their activity and reduce side effects; some of these derivatives turned out to be potent antineoplastic agents.…”

“…Both ursolic acid 3 and pomolic acid 7 induce apoptosis [21] by binding to protein kinase B/Akt1 through hydrogen bridges formed by the carboxyl group of their molecule and the carboxyl group of the amino acid residue Glu234 of the kinase. The carboxyl groups also participate in the formation of interaction of the studied triterpene acids with MDM2.…”

Ursolic and Oleanolic Acids: Plant Metabolites with Neuroprotective Potential

“…In other in vitro glioblastoma models, UA (at 17.5 µM) has been shown to induce necrosis in TMZ-resistant human DBTRG-05MG cells through mitochondrial permeability transition pore opening and ATP level decline [ 120 ] or at 40 µM concentration UA treatment has led to cell cycle arrest at G1 phase, endoplasmic reticulum stress-induced JNK activation and autophagy in U-87 MG cells [ 121 ]. However, UA from Chamaenerion angustifolium at 50 µM concentration induced both apoptosis and necrosis in U-87 MG cells, and this effect was explained by UA interaction with the PI3K/Akt signalling pathway as predicted by molecular docking [ 122 ]. UA (at 12.5 µM) has also enhanced the cytotoxicity of TMZ in human LN-18 and T98G glioblastoma cells by downregulating MGMT expression, and at 50 mg/kg UA potentiated the efficacy of TMZ in BALB/c mice with LN-18 xenograft [ 123 ].…”

Synthesis and Cytotoxicity of Sulfanyl, Sulfinyl and Sulfonyl Group Containing Ursane Conjugates with 1,3,4‐Oxadiazoles and 1,2,4‐Triazoles

“…[31][32][33][34] We have previously obtained data on the mechanisms of the cytotoxic action of ursolic acid derivatives. [35,36] In this regard, we carried out molecular modeling of the possible interaction of new thioether-1,2,4-triazole-ursane hybrids 7 g, 7 h which demonstrated the best activity and selectivity with MDM2 to propose a hypothesis of their molecular mechanism of action. The docking scores for the new derivatives 7 g and 7 h are given in Table 3.…”