Phytochemicals have been suggested as an effective strategy for cancer prevention. Within this context, triterpene betulinic acid (BA) exhibits several biological properties but its chemopreventive effect has not been fully demonstrated. The present study investigated the antigenotoxic potential of BA against doxorubicin (DXR)-induced genotoxicity using the mouse peripheral blood micronucleus assay, as well as its anticarcinogenic activity against 1,2dimethylhydrazine (DMH)-induced colorectal lesions in rats. Micronuclei (MN) assay and aberrant crypt foci assay were used to assess the antigenotoxic and the anticarcinogenic potential, respectively. The molecular mechanisms underlying the anticarcinogenic activity of BA were evaluated by assessing anti-inflammatory (COX-2) and antiproliferative (PCNA) pathways. The results demonstrated that BA at the dose of 0.5 mg/kg bodyweight exerted antigenotoxic effects against DXR, with a reduction of 70.2% in the frequencies of chromosomal damage. Animals treated with BA showed a 64% reduction in the number of preneoplastic lesions when compared to those treated with the carcinogen alone. The levels of COX-2 and PCNA expression in the colon were significantly lower in animals treated with BA and DMH compared to those treated with the carcinogen alone. The chemopreventive effect of BA is related, at least in part, to its antiproliferative and anti-inflammatory activity, indicating a promising potential of this triterpene in anticancer therapies, especially for colorectal cancer.

中文翻译：

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白桦脂酸通过抑制啮齿动物的 COX-2 和 PCNA 发挥抗原毒性和抗癌活性

植物化学物质已被认为是预防癌症的有效策略。在这种情况下，三萜白桦脂酸 (BA) 具有多种生物学特性，但其化学预防作用尚未得到充分证明。本研究使用小鼠外周血微核试验研究了 BA 对多柔比星 (DXR) 诱导的基因毒性的抗原毒性潜力，以及其对 1,2 二甲基肼 (DMH) 诱导的大鼠结肠直肠病变的抗癌活性。微核 (MN) 测定和异常隐窝病灶测定分别用于评估抗原毒性和抗癌潜力。通过评估抗炎 (COX-2) 和抗增殖 (PCNA) 途径评估了 BA 抗癌活性的分子机制。结果表明，0.5 mg/kg 体重的 BA 对 DXR 具有抗原毒性作用，染色体损伤频率降低了 70.2%。与仅用致癌物治疗的动物相比，用 BA 治疗的动物的癌前病变数量减少了 64%。与仅用致癌物治疗的动物相比，用 BA 和 DMH 治疗的动物的结肠中 COX-2 和 PCNA 表达水平显着降低。BA 的化学预防作用至少部分与其抗增殖和抗炎活性有关，这表明这种三萜在抗癌治疗中具有广阔的潜力，尤其是对于结直肠癌。染色体损伤的频率为 2%。与仅用致癌物治疗的动物相比，用 BA 治疗的动物的癌前病变数量减少了 64%。与仅用致癌物治疗的动物相比，用 BA 和 DMH 治疗的动物的结肠中 COX-2 和 PCNA 表达水平显着降低。BA 的化学预防作用至少部分与其抗增殖和抗炎活性有关，这表明这种三萜在抗癌治疗中具有广阔的潜力，尤其是对于结直肠癌。染色体损伤的频率为 2%。与仅用致癌物治疗的动物相比，用 BA 治疗的动物的癌前病变数量减少了 64%。与仅用致癌物治疗的动物相比，用 BA 和 DMH 治疗的动物的结肠中 COX-2 和 PCNA 表达水平显着降低。BA 的化学预防作用至少部分与其抗增殖和抗炎活性有关，这表明这种三萜在抗癌治疗中具有广阔的潜力，尤其是对于结直肠癌。与仅用致癌物治疗的动物相比，用 BA 和 DMH 治疗的动物的结肠中 COX-2 和 PCNA 表达水平显着降低。BA 的化学预防作用至少部分与其抗增殖和抗炎活性有关，这表明这种三萜在抗癌治疗中具有广阔的潜力，尤其是对于结直肠癌。与仅用致癌物治疗的动物相比，用 BA 和 DMH 治疗的动物的结肠中 COX-2 和 PCNA 表达水平显着降低。BA 的化学预防作用至少部分与其抗增殖和抗炎活性有关，这表明这种三萜在抗癌治疗中具有广阔的潜力，尤其是对于结直肠癌。