Department of Biotechnology and Laboratory Science in Medicine, National Yang Ming Chiao Tung University, Taipei, 11221, Taiwan.
Center for Teacher Education, National Tsing Hua University, Hsinchu, Taiwan; Department of Applied Science, National Tsing Hua University, Nanda Campus, Hsinchu, Taiwan.
Food Chem Toxicol. 2021 Dec;158:112617. doi: 10.1016/j.fct.2021.112617. Epub 2021 Oct 30.
This study investigated the effects and molecular mechanisms of ε-viniferin and α-viniferin in non-small cell lung cancer cell line A549, melanoma cell line A2058, and osteosarcoma cell lines HOS and U2OS. Results showed ε-viniferin having antiproliferative effects on HOS, U2OS, and A549 cells. Compared with ε-viniferin at the same concentration, α-viniferin had higher antiproliferative effects on HOS cells, but not the same effect on U2OS and A549 cells. Lower dose combination of α-viniferin and ε-viniferin had more synergistic effects on A549 cells than either drug alone. α-Viniferin induced apoptosis in HOS cells by decreasing expression of phospho-c-Jun-N-terminal kinase 1/2 (p-JNK1/2) and increasing expression of cleaved Poly (ADP-ribose) polymerase (PARP), whereas α-viniferin in combination with ε-viniferin induced apoptosis in A549 cells by decreasing expression of phospho-protein kinase B (p-AKT) and increasing expression of cleaved PARP and cleaved caspase-3. ε-Viniferin and α-viniferin have not been studied using in vivo tumor models for cancer. This research is the first showing that ε-viniferin treatment resulted in significant inhibition of tumor growth in A549-cell xenograft-bearing nude mice compared with the control group. Consequently, ε-viniferin and α-viniferin may prove to be new approaches and effective therapeutic agents for osteosarcoma and lung cancer treatment.
本研究探讨了 ε-viniferin 和 α-viniferin 在非小细胞肺癌细胞系 A549、黑色素瘤细胞系 A2058 和骨肉瘤细胞系 HOS 和 U2OS 中的作用和分子机制。结果表明，ε-viniferin 对 HOS、U2OS 和 A549 细胞具有增殖抑制作用。与相同浓度的 ε-viniferin 相比，α-viniferin 对 HOS 细胞的增殖抑制作用更高，但对 U2OS 和 A549 细胞的作用相同。α-viniferin 与 ε-viniferin 的低剂量联合对 A549 细胞的协同作用大于单独使用任何一种药物。α-viniferin 通过降低磷酸化 c-Jun-N-末端激酶 1/2（p-JNK1/2）的表达和增加裂解多聚（ADP-核糖）聚合酶（PARP）的表达诱导 HOS 细胞凋亡，而 α-viniferin 与 ε-viniferin 联合诱导 A549 细胞凋亡通过降低磷酸化蛋白激酶 B（p-AKT）的表达和增加裂解 PARP 和裂解 caspase-3 的表达。尚未在癌症的体内肿瘤模型中研究过 ε-viniferin 和 α-viniferin。这项研究首次表明，与对照组相比，ε-viniferin 治疗导致 A549 细胞异种移植裸鼠肿瘤生长明显抑制。因此，ε-viniferin 和 α-viniferin 可能被证明是骨肉瘤和肺癌治疗的新方法和有效治疗剂。
