Department of Nutrition, Dietetics, and Food Science, Brigham Young University, Provo, UT 84602, USA.
Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA.
Molecules. 2017 Nov 14;22(11):1968. doi: 10.3390/molecules22111968.
Triple-negative breast cancer is a highly aggressive subtype of breast cancer. Frequently, breast cancer cells modulate their calcium signaling pathways to optimize growth. Unique calcium pathways in breast cancer cells could serve as a way to target tumorigenic cells without affecting normal tissue. Resveratrol has previously been shown to activate calcium signaling pathways. We use cell viability, single-cell calcium microscopy, and RT-PCR assays to determine the activity and mechanism of three different 4'-esterified resveratrol derivatives. We demonstrate that two of the derivatives reduce cell viability more effectively than resveratrol in MDA-MB-231 human breast cancer cells. The derivatives also activate similar pro-apoptotic calcium signaling pathways. In particular, the pivalated and butyrated resveratrol derivatives are intriguing putative chemotherapeutics because they are more effective at decreasing cell viability in vitro and inhibiting the plasma membrane Ca-ATPase, a protein that is often modulated in breast cancer.
三阴性乳腺癌是一种侵袭性很强的乳腺癌亚型。通常，乳腺癌细胞会调节其钙信号通路以优化生长。乳腺癌细胞中独特的钙通路可以作为一种靶向致癌细胞而不影响正常组织的方法。白藜芦醇先前已被证明能激活钙信号通路。我们使用细胞活力、单细胞钙显微镜和 RT-PCR 测定来确定三种不同 4′-酯化白藜芦醇衍生物的活性和机制。我们证明，两种衍生物在 MDA-MB-231 人乳腺癌细胞中比白藜芦醇更有效地降低细胞活力。这些衍生物还激活了类似的促凋亡钙信号通路。特别是特戊酸和丁酸白藜芦醇衍生物是很有前途的潜在化疗药物，因为它们在体外更有效地降低细胞活力，并抑制质膜 Ca-ATP 酶，这种蛋白质在乳腺癌中经常被调节。
