Peterson Joshua A, Crowther Colton M, Andrus Merritt B, Kenealey Jason D
Department of Nutrition, Dietetics and Food Science, Brigham Young University, Provo, UT, USA.
Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA.
Biochem Biophys Rep. 2019 Jul 20;19:100667. doi: 10.1016/j.bbrep.2019.100667. eCollection 2019 Sep.
Resveratrol (RES) is a putative chemotherapeutic naturally found in grapes, peanuts, and Japanese knotweed. Previous studies demonstrate that RES modulates calcium signaling as part of its chemotherapeutic activity. In this study, we determined the chemotherapeutic activity of three RES esters that have been modified at the 4' hydroxyl by the addition of pivalate, butyrate, and isobutyrate. All of the RES derivatives disrupted the calcium signaling in prostate cancer cells more than the parent compound, RES. Further, we demonstrate that the RES derivatives may disrupt the calcium homeostasis by activating calcium release from the endoplasmic reticulum and inhibiting plasma membrane Ca-ATPase. The pivalated and butyrated RES derivatives decreased cell viability significantly more than RES. Because pivalated and butyrated RES are more effective than RES at targeting calcium signaling pathways, pivalated and butyrated RES may serve as more effective chemotherapeutics.
白藜芦醇（RES）是一种天然存在于葡萄、花生和虎杖中的潜在化疗药物。先前的研究表明，RES作为其化疗活性的一部分，可调节钙信号传导。在本研究中，我们测定了三种在4'羟基处通过添加新戊酸酯、丁酸酯和异丁酸酯进行修饰的RES酯的化疗活性。所有RES衍生物对前列腺癌细胞钙信号传导的破坏作用均大于母体化合物RES。此外，我们证明RES衍生物可能通过激活内质网钙释放和抑制质膜钙ATP酶来破坏钙稳态。新戊酸化和丁酸化的RES衍生物比RES显著降低细胞活力。由于新戊酸化和丁酸化的RES在靶向钙信号通路方面比RES更有效，新戊酸化和丁酸化的RES可能作为更有效的化疗药物。
