Chemopreventive potential of β-Sitosterol in experimental colon cancer model - an In vitro and In vivo study
Chemopreventive potential of β-Sitosterol in experimental colon cancer model - an In vitro and In vivo study
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DOI：
10.1186/1472-6882-10-24
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发表时间：
2010-06-04
影响因子：
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通讯作者：
Al Numair, Khalid S.
中科院分区：
文献类型：
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作者：
Baskar, Albert A.;Ignacimuthu, Savarimuthu;Al Numair, Khalid S.
背景：马利筋（Asclepias curassavica Linn）。是印度西高止山脉部落人民用来治疗痔疮、淋病、蛔虫感染和腹部肿瘤的传统药用植物。我们使用体外和体内模型确定了从 A. curassavica 中分离出的 β-谷甾醇对结肠癌的保护作用。 ，使其成为结肠癌的潜在抗癌药物。方法：根据生物测定引导的分级分离，分离出活性分子，并根据光谱证据鉴定为β-谷甾醇。诱导细胞凋亡的能力是通过其体外抗自由基活性、使用人结肠腺癌和正常猴肾细胞系进行的细胞毒性研究以及人结肠癌细胞系 (COLO 320 DM) 中 β-连环蛋白和增殖细胞核抗原 (PCNA) 的表达来确定的。通过向雄性 Wistar 大鼠注射 1,2-二甲基肼（DMH，20 mg/kg b.w.）并在整个 16 周的实验期间以 5、10 和 20 mg/kg b.w. 补充 β-谷甾醇，评估 β-谷甾醇在结肠癌发生中的化学预防潜力。结果：β-谷甾醇诱导显着的剂量依赖性生长 抑制 COLO 320 DM 细胞 (IC50 266.2 mu M)，通过清除活性氧诱导细胞凋亡，并抑制人结肠癌细胞中 β-连环蛋白和 PCNA 抗原的表达。 β-谷甾醇补充剂以剂量依赖性方式减少了 DMH 引发的大鼠中异常隐窝的数量和隐窝的多样性，并且没有毒性作用。结论：我们发现 10-20 mg/kg b.w 的剂量。 β-谷甾醇对未来的体内研究有效。 β-谷甾醇凭借其体外自由基猝灭能力而具有化学预防潜力，并且对正常细胞的毒性最小。它还可以减弱 β-连环蛋白和 PCNA 的表达，使其成为结肠癌的潜在抗癌药物。
Background: Asclepias curassavica Linn. is a traditional medicinal plant used by tribal people in the western ghats, India, to treat piles, gonorrhoea, roundworm infestation and abdominal tumours. We have determined the protective effect of beta-sitosterol isolated from A. curassavica in colon cancer, using in vitro and in vivo models. , making it a potential anticancer drug for colon carcinogenesis.Methods: The active molecule was isolated, based upon bioassay guided fractionation, and identified as beta-sitosterol on spectral evidence. The ability to induce apoptosis was determined by its in vitro antiradical activity, cytotoxic studies using human colon adenocarcinoma and normal monkey kidney cell lines, and the expression of beta-catenin and proliferating cell nuclear antigen (PCNA) in human colon cancer cell lines (COLO 320 DM). The chemopreventive potential of beta-sitosterol in colon carcinogenesis was assessed by injecting 1,2-dimethylhydrazine (DMH, 20 mg/kg b.w.) into male Wistar rats and supplementing this with beta-sitosterol throughout the experimental period of 16 weeks at 5, 10, and 20 mg/kg b.w.Results: beta-sitosterol induced significant dose-dependent growth inhibition of COLO 320 DM cells (IC50 266.2 mu M), induced apoptosis by scavenging reactive oxygen species, and suppressed the expression of beta-catenin and PCNA antigens in human colon cancer cells. beta-sitosterol supplementation reduced the number of aberrant crypt and crypt multiplicity in DMH-initiated rats in a dose-dependent manner with no toxic effects.Conclusion: We found doses of 10-20 mg/kg b.w. beta-sitosterol to be effective for future in vivo studies. beta-sitosterol had chemopreventive potential by virtue of its radical quenching ability in vitro, with minimal toxicity to normal cells. It also attenuated beta-catenin and PCNA expression, making it a potential anticancer drug for colon carcinogenesis.