IC50: 2.5 μg/mL for P3HR1 cells; 17.79 μg/mL for myelogenous leukemia K562 cells
Ursolic acid, an ursane-type pentacyclic triterpenic acid, belongs to the cyclosqualenoid family, has been reported to be useful in cancer prevention and treatment. Several inflammatory signaling cascades including nuclear factor-kB and cyclooxygenase-2 have been linked with different stages of cancer progression.
In vitro: Ursolic acid was reported to suppress the proliferation of a number of tumor cells, induce apoptosis and inhibit metastasis, tumor promotion, and angiogenesis. Ursolic acid could inhibit NF-kB activation induced by carcinogenic agents through the suppression of IkBa kinase and p65/RelA phosphorylation [1].
In vivo: In vivo, ursolic acid has been reported to inhibit tumor growth in various cancer animal models. In nude mice, ursolic acid treatment for 6 weeks inhibited the growth of DU145 cells without any significant effect on body weight. In addition, ursolic acid treatment produced chemopreventive effects in the transgenic adenocarcinoma of mouse prostate mouse model [1].
Clinical trial: Sixty-three subjects received a single dose of ursolic acid liposomes. The clinical results showed that liposomal ursolic acid had manageable toxicities with MTD of 98 mg/m2. The DLT were primarily diarrhea and hepatotoxicity. Additionally, ursolic acid liposomeal formulation had a linear pharmacokinetic profile [1].
IC50：对P3HR1细胞为2.5μg/mL；对骨髓性白血病K562细胞为17.79μg/mL。
熊果酸是一种五环三萜三酸，属于环角鲨烷类，已被报道在癌症预防和治疗中有用。多种炎症信号级联，包括核因子-kB和环氧合酶-2已被与不同阶段的癌症进展联系起来。
体外：据报道，熊果酸可以抑制多种肿瘤细胞的增殖，诱导凋亡并抑制转移、肿瘤促进和血管生成。熊果酸可通过抑制IkBa激酶和p65/RelA磷酸化抑制致癌剂诱导的NF-kB激活[1]。
体内：在体内，已报道熊果酸抑制了多种癌症动物模型中的肿瘤生长。在裸鼠中，6周的熊果酸治疗抑制了DU145细胞的生长，而对体重没有任何显著影响。此外，熊果酸治疗在转基因小鼠前列腺腺癌模型中产生了化学预防效应[1]。
临床试验：63名受试者接受了单剂量熊果酸脂质体。临床结果显示，脂质体熊果酸具有可管理的毒性，MTD为98 mg/m2。DLT主要是腹泻和肝毒性。此外，熊果酸脂质体制剂具有线性药代动力学特征[1]。
Reference:
[1] Shanmugam MK,Dai X,Kumar AP,Tan BK,Sethi G,Bishayee A. Ursolic acid in cancer prevention and treatment: molecular targets, pharmacokinetics and clinical studies. Biochem Pharmacol.2013 Jun 1;85(11):1579-87.