Curcumin analogues exhibit enhanced growth suppressive activity in human pancreatic cancer cells.
Curcumin analogues exhibit enhanced growth suppressive activity in human pancreatic cancer cells.
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DOI：
10.1097/cad.0b013e32832afc04
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发表时间：
2009-07
影响因子：
2.3
通讯作者：
Lin J
中科院分区：
文献类型：
--
作者：
Friedman L;Lin L;Ball S;Bekaii-Saab T;Fuchs J;Li PK;Li C;Lin J
姜黄素是一种黄色色素，是姜黄的活性成分，已被证明可以防止几种癌症的发生和肿瘤的发展。然而，它的低生物利用度和效力阻止了它在大多数化疗应用中有效。解决这一问题的一个潜在方法是合成姜黄素类似物。我们在人类胰腺癌细胞系中测试了两种类似物FLLL11和FLLL12的功效。我们比较了姜黄素与FLLL11和FLLL12对五种不同胰腺癌细胞系细胞活力的影响。虽然这三种化合物都能降低所有细胞系的活性，但FLLL11和FLLL12 （IC50值分别在0.28 ~ 3.2和0.91 ~ 3.43λμmol/l之间）比姜黄素（IC50值在8.67 ~ 20.35λμmol/l之间）的活性强得多。此外，FLLL11和FLLL12抑制信号转导和转录激活因子3和AKT的磷酸化，这两种细胞信号通路在许多形式的癌症中经常被发现持续活跃。此外，在胰腺癌细胞系中，FLLL11和FLLL12比姜黄素更有效地诱导细胞凋亡，这可以通过增加PARP和caspase-3的切割来证明。这些结果表明，姜黄素类似物FLLL11和FLLL12在抑制细胞活力和诱导细胞凋亡方面比姜黄素更有效，可能具有转化为胰腺癌化学预防或治疗药物的潜力。
Curcumin, a yellow pigment and the active component of turmeric, has been shown to protect against carcinogenesis and prevent tumor development in several types of cancer. However, its low bioavailability and potency prevent it from being effective in most chemotherapeutic applications. One potential means of circumventing this problem has been the creation of synthetic curcumin analogues. We tested the efficacy of two such analogues, known as FLLL11 and FLLL12, in human pancreatic cancer cell lines. We compared the impact of curcumin with FLLL11 and FLLL12 on cell viability in five different pancreatic cancer cell lines. Although all three compounds were capable of lowering viability in all cell lines tested, FLLL11 and FLLL12 (IC50 values between 0.28–3.2 and 0.91–3.43λμmol/l, respectively) were substantially more potent than curcumin (IC50 values between 8.67 and 20.35λμmol/l). In addition, FLLL11 and FLLL12 inhibited phosphorylation of signal transducer and activator of transcription 3 and AKT, two cell signaling pathways frequently found persistently active in many forms of cancer. Furthermore, FLLL11 and FLLL12 were found to be more effective than curcumin in inducing apoptosis as evidenced by increased cleavage of PARP and caspase-3 in pancreatic cancer cell lines. These results indicate that the curcumin analogues, FLLL11 and FLLL12, are more effective than curcumin in inhibiting cell viability and inducing apoptosis, and may have translational potential as chemopreventive or therapeutic agents for pancreatic cancer.