Sulforaphane induces cell cycle arrest and apoptosis in murine osteosarcoma cells in vitro and inhibits tumor growth in vivo.
Sulforaphane induces cell cycle arrest and apoptosis in murine osteosarcoma cells in vitro and inhibits tumor growth in vivo.
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DOI：
10.3892/or.18.5.1263
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发表时间：
2007-11
期刊：
影响因子：
4.2
通讯作者：
T. Matsui;H. Murata;T. Sakabe;Y. Sowa;N. Horie;Ryoko Nakanishi;T. Sakai;T. Kubo
中科院分区：
文献类型：
--
作者：
T. Matsui;H. Murata;T. Sakabe;Y. Sowa;N. Horie;Ryoko Nakanishi;T. Sakai;T. Kubo
萝卜硫素 (SFN) 是一种天然存在的异硫氰酸酯，由于其有效的抗癌作用而成为一种有吸引力的药物。 SFN 在体外和体内抑制多种癌细胞的增殖。在这项研究中，我们报告 SFN 抑制培养的鼠骨肉瘤 LM8 细胞的增殖。 20微摩尔SFN完全抑制LM8细胞的生长并导致G2/M期停滞。 SFN 诱导 p21(WAF1/CIP1) 蛋白的表达，导致细胞周期以剂量依赖性方式停滞。 SFN 诱导细胞凋亡，其特征是出现亚 G1 DNA 含量的细胞以及 caspase-3 的裂解和激活。我们发现，SFN 在人骨肉瘤 MG63 细胞中以不依赖于 p53 的方式诱导生长停滞并上调 p21（WAF1/CIP1）蛋白的表达。我们发现，在临床前动物模型中，腹腔注射 SFN（1 或 2 毫克，5 次/周）可显着抑制 LM8 异种移植物的生长，其生长量仅为对照的 30% 以下，且不会引起任何毒性。在骨肉瘤细胞中，我们的研究结果为 SFN 对抗肿瘤晚期生长的功效提供了体内证据。我们发现 SFN 诱导骨肉瘤细胞的细胞周期停滞和细胞凋亡，并抑制肿瘤异种移植物的生长。此外，SFN 是骨肉瘤细胞中 p21(WAF1/CIP1) 的有效诱导剂。这些结果提出了 SFN 可能成为骨肉瘤分子靶向化疗的有希望的候选者的可能性。
Sulforaphane (SFN), a naturally occurring isothiocyanate, is an attractive agent due to its potent anticancer effects. SFN suppresses the proliferation of various cancer cells in vitro and in vivo. In this study, we report that SFN inhibited the proliferation of cultured murine osteosarcoma LM8 cells. Twenty micromolar SFN completely inhibited the growth of LM8 cells and caused G2/M-phase arrest. SFN induced the expression of p21(WAF1/CIP1) protein causing the cell cycle arrest in a dose-dependent manner. SFN induced apoptosis which was characterized by the appearance of cells with sub-G1 DNA content and the cleavage and activation of caspase-3. We showed that SFN induced the growth arrest and up-regulated the expression of p21(WAF1/CIP1) protein in a p53-independent manner in human osteosarcoma MG63 cells. We found that intraperitoneal administration of SFN (1 or 2 mg, 5 times/week) significantly inhibited the growth of LM8 xenografts to <30% of the controls in a preclinical animal model without causing any toxicity. In osteosarcoma cells, our findings provide in vivo evidence for the efficacy of SFN against the advanced growth of tumor. We showed that SFN induces cell cycle arrest and apoptosis in osteosarcoma cells and inhibits tumor xenograft growth. Furthermore, SFN is a potent inducer of p21(WAF1/CIP1) in osteosarcoma cells. These results raise the possibility that SFN may be a promising candidate for molecular-targeting chemotherapy against osteosarcoma.