In vitro and in vivo anticancer activity evaluation of ursolic acid derivatives

Evaluation of some biological activities of Abelia triflora R Br (Caprifoliaceae) constituents

“…Our results also proved that ursolic acid was the most active as cytotoxic constituent. This is in agreement with previous studies which confirmed the great potential of this triterpene acid as cytotoxic agent on different cell lines [21,22]. It also proves that the hydroxylation of ursolic acid at positions 2 and 21 may be responsible for lowering its antiinflammatory and cytotoxic potential.…”

Ursolic acid in cancer prevention and treatment: Molecular targets, pharmacokinetics and clinical studies

“…The same group of researchers also synthesized another ursolic acid derivative, 3b-acetoxy-urs-12-en-28-oyl-1-monoglyceride that was found to trigger the death of BGC-823 cells by inducing apoptosis via the mitochondria pathway [69]. Ursolic acid derivative, N-[3b-acetoxy-urs-12-en-28-oyl]-2-aminodiethanol, was tested with increasing concentrations of test compound for 24 h. Dose-dependent induction of apoptosis was observed in various tumor cell lines including, HepG2, BGC-823, SH-SY5Y, HeLa, and HELF [70]. A series of new heterocyclic derivatives of ursolic acid showed potent antiproliferative activity and induction of p53, p21waf1 and NOXA against pancreatic cancer cell lines AsPC-1 [71].…”

“…It was observed that ursolic acid down-regulated activation of various pro-inflammatory mediators including, NF-kB, STAT3, AKT and IKKa/b phosphorylation in the dorsolateral prostate (DLP) tissues that correlated with the decreased serum levels of TNF-a and IL-6 [74]. In vivo studies using H22 xenografts in Kunming mice were conducted by Shao et al [70] with a novel ursolic acid derivative (compound 14) at doses of 50, 100 and 150 mg/kg body weight.…”

“…[34] Reduced the expression of VEGF and increased the expression of caspase-3 in tumor tissues Transgenic adenocarcinoma of mouse prostate (animal model: TRAMP) -dietary dose (1%, w/w) Ursolic acid in TRAMP mice delayed formation of prostate intraepithelial neoplasia, inhibited progression of PIN to adenocarcinoma and demonstrated markedly reduced tumor growth without any significant effects on total body weight and prolonged overall survival [74] Down-regulated the expression of COX-2, cyclin D1 and up-regulated the expression of caspase-3 [74] Reduced CXCR4 expression in tumor tissues of 36 weeks old TRAMP mice [30] Hepatocellular carcinoma (animal model: Kunming mice) -intraperitoneal injection Inhibited tumor growth in subcutaneously implanted tumor in a dose-dependent manner [70] Hepatocellular carcinoma (animal model: Wistar rat) -oral feeding Inhibited diethylnitrosamine-induced and phenobarbital-promoted liver cancer [78] Reduced oxidative stress and free radicals in liver of Wistar rats [78] Colorectal carcinoma (animal model: male nude mice) -intraperitoneal administration Inhibited colonic adenocarcinomas in an orthotopic mouse model and this effect was enhanced in the presence of capecitabine [39] Inhibited proliferation marker Ki-67 and microvessel density CD-31with concomitant suppression of NF-kB, STAT3 and b-catenin Breast carcinoma (animal model: overiectomized female C57BL/6 mice) -dietary dose Inhibited syngenic MMTV-Wnt-1 mammary tumors injected in mammary fat pad [77] Inhibited AKT/mTOR signaling pathway and induced apoptosis in tumors [76] Skin carcinoma (animal model: mice) Inhibited skin cancer growth by decreasing epidermal thickness [80] Gastric cancer (animal model: male nude mice) Inhibited the growth of gastric cancer BGC-803 xenograft and induced apoptosis in tumors [57] Abbreviations: Bcl2, B-cell lymphoma 2; COX-2, cyclooxygenase-2; DR, death receptor; EGFR, epidermal growth factor receptor; HER2, human epidermal growth factor receptor 2; IFN-g, interferon-gamma; IkB, inhibitory subunit of NF-kB; IKK, IkB kinase; IL, interleukin; iNOS, inducible nitric oxide synthase; IAPs, inhibitor of apoptosis; LOX, lipoxygenase; MMP, matrix metalloproteinase; MAPK, mitogen-activated protein kinase; NF-kB, nuclear factor-kB; PARP, poly ADP ribose polymerase; ROS, Reactive oxygen species; RNS, Reactive nitrogen species; STAT3, signal transducer and activator of transcription 3; SH-PTP1, protein tyrosine phosphatase-SHP1; TRAMP, transgenic adenocarcinoma of prostate; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand; TNF-a, tumor necrosis factor; TGF-b, transforming growth factor beta; TIMP-3, Tissue inhibitor of metalloproteinase 3; VCAM-1, vascular cell adhesion molecule 1; VEGF, vascular endothelial growth factor.…”

Permeation-enhancing properties of Nepeta cataria var. citriodora dry extract

“…This compound is of a great interest because of its anti-inflammatory, anti-angiogenic and anticancer activities [4]. According to recently published studies, ursolic acid may improve epidermal permeability barrier function of skin and stimulate the differentiation of epidermal keratinocytes [5].…”