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1,8-桉叶素对结肠癌的抗肿瘤作用。

Antitumor effect of 1, 8-cineole against colon cancer.

机构信息

Department of Surgery, Teikyo University Chiba Medical Center, Ichihara, Japan.

出版信息

Oncol Rep. 2013 Dec;30(6):2647-52. doi: 10.3892/or.2013.2763. Epub 2013 Oct 1.

Abstract

Several essential oils possess pharmacological effects. Among the various constituents of essential oils, 1, 8-cineole has been shown to possess pharmacological effects such as anti-bacterial and anti-inflammatory effects. The effect of 1, 8-cineole on human colorectal cancer cells, however, has not reported previously. In this study, we have investigated the anti-proliferative effect of 1, 8-cineole on human colon cancer cell lines HCT116 and RKO by WST-8 and BrdU assays. The cytotoxicity of 1, 8-cineole was investigated by LDH activity and TUNEL staining. The mechanism of apoptosis by 1, 8-cineole was determined by western blot analyses. In in vivo study, RKO cells were injected into the SCID mice and the effect of 1, 8-cineole was investigated. Specific induction of apoptosis, not necrosis, was observed in human colon cancer cell lines HCT116 and RKO by 1, 8-cineole. The treatment with 1, 8-cineole was associated with inactivation of survivin and Akt and activation of p38. These molecules induced cleaved PARP and caspase-3, finally causing apoptosis. In xenotransplanted SCID mice, the 1, 8-cineole group showed significantly inhibited tumor progression compared to the control group. These results indicated 1, 8-cineole suppressed human colorectal cancer proliferation by inducing apoptosis. Based on these studies 1, 8-cineole would be an effective strategy to treat colorectal cancer.

摘要

几种精油具有药理学作用。在精油的各种成分中,1,8-桉叶素已被证明具有药理学作用,如抗菌和抗炎作用。然而,1,8-桉叶素对人结直肠癌细胞的作用以前尚未报道过。在这项研究中,我们通过 WST-8 和 BrdU 测定法研究了 1,8-桉叶素对人结肠癌细胞系 HCT116 和 RKO 的抗增殖作用。通过 LDH 活性和 TUNEL 染色研究了 1,8-桉叶素的细胞毒性。通过 Western blot 分析确定了 1,8-桉叶素诱导凋亡的机制。在体内研究中,将 RKO 细胞注射到 SCID 小鼠中,并研究了 1,8-桉叶素的作用。1,8-桉叶素特异性诱导人结肠癌细胞系 HCT116 和 RKO 凋亡,而不是坏死。1,8-桉叶素处理与生存素和 Akt 的失活以及 p38 的激活有关。这些分子诱导裂解的 PARP 和 caspase-3,最终导致凋亡。在异种移植的 SCID 小鼠中,与对照组相比,1,8-桉叶素组显示出明显抑制肿瘤进展的作用。这些结果表明,1,8-桉叶素通过诱导细胞凋亡抑制人结直肠癌细胞的增殖。基于这些研究,1,8-桉叶素将是治疗结直肠癌的有效策略。

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