Hutzen Brian, Friedman Lauren, Sobo Matthew, Lin Li, Cen Ling, De Angelis Stephanie, Yamakoshi Hiroyuki, Shibata Hiroyuki, Iwabuchi Yoshiharu, Lin Jiayuh
Department of Pediatrics, Tohoku University, Sendai, Japan.
Int J Oncol. 2009 Oct;35(4):867-72. doi: 10.3892/ijo_00000401.
Curcumin has numerous anti-carcinogenic properties, but low bioavailability prevents its use in chemotherapeutic applications. One strategy for circumventing this problem has been the creation of synthetic analogues. We tested the efficacy of an analogue known as GO-Y030 in human breast and pancreatic cancer cells. We compared the impact of curcumin and GO-Y030 on the breast cancer cell line MDA-MB-231 and pancreatic cancer cell lines, PANC-1, HPAC and BXPC-3. Both compounds reduced cell viability and induced apoptosis, but GO-Y030 was substantially more potent. We also demonstrated that GO-Y030 was capable of interfering with STAT3, a persistently activated transcription factor in many cancer types. GO-Y030 inhibited STAT3 phosphorylation and transcriptional activity whereas comparable dosages of curcumin had little or no effect. These results indicate that GO-Y030 is a potent inhibitor of cell viability and STAT3 activation, and may thus have potential as a therapeutic agent for cancers expressing high levels of activated STAT3.
姜黄素具有多种抗癌特性，但生物利用度低限制了其在化疗中的应用。解决这一问题的一种策略是合成类似物。我们测试了一种名为GO-Y030的类似物对人乳腺癌和胰腺癌细胞的疗效。我们比较了姜黄素和GO-Y030对乳腺癌细胞系MDA-MB-231和胰腺癌细胞系PANC-1、HPAC及BXPC-3的影响。两种化合物均降低了细胞活力并诱导了细胞凋亡，但GO-Y030的效力要强得多。我们还证明，GO-Y030能够干扰信号转导和转录激活因子3（STAT3），STAT3是许多癌症类型中持续激活的转录因子。GO-Y030抑制STAT3磷酸化和转录活性，而同等剂量的姜黄素几乎没有影响。这些结果表明，GO-Y030是细胞活力和STAT3激活的有效抑制剂，因此可能具有作为治疗高表达激活型STAT3癌症的治疗剂的潜力。
