含硫代亚磺酸盐基团的天然化合物大蒜素作为跨膜蛋白 16A (TMEM16A) 离子通道抑制剂用于肺癌的食品辅助治疗,Journal of Agricultural and Food Chemistry

当前位置： X-MOL 学术 › J. Agric. Food Chem. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

含硫代亚磺酸盐基团的天然化合物大蒜素作为跨膜蛋白 16A (TMEM16A) 离子通道抑制剂用于肺癌的食品辅助治疗
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2022-12-27 , DOI: 10.1021/acs.jafc.2c06723
Xue Bai ₁ , Yana Cheng ₁ , Haifu Wan _{1,

2} , Shuting Li ₁ , Xianjiang Kang ₁ , Shuai Guo _{1,

2}

Affiliation

癌症是最严重的恶性疾病之一，化疗是癌症的主要临床治疗方法。然而，化疗不可避免地会产生耐药性，伴随而来的还有副作用。辅助治疗是提高化疗药物敏感性、减少副作用的有效途径。这项研究发现，大蒜的活性成分大蒜素是跨膜蛋白 16A (TMEM16A) 的抑制剂，而后者是肺腺癌的新型药物靶点。大蒜素浓度依赖性地抑制 TMEM16A 电流，IC_{为 50}24.35 ± 4.14 μM。与 TMEM16A 的 R535A/E624A/E633A 残基结合的大蒜素硫代亚磺酸盐部分阻断离子传输功能并下调 TMEM16A 蛋白表达，影响丝裂原活化蛋白激酶信号转导。然后，大蒜素降低LA795细胞的活力和迁移，并诱导细胞凋亡。此外，多靶点联合给药结果表明，3.56 mg/kg大蒜素和3 mg/kg顺铂联合给药的治疗效果优于两种药物单独叠加给药，表明大蒜素和顺铂的抗癌作用具有协同作用。此外，低浓度联合给药也避免了顺铂对小鼠的副作用。

"点击查看英文标题和摘要"

Natural Compound Allicin Containing Thiosulfinate Moieties as Transmembrane Protein 16A (TMEM16A) Ion Channel Inhibitor for Food Adjuvant Therapy of Lung Cancer

Cancer is one of the most serious malignant diseases, and chemotherapy is cancer’s main clinical treatment method. However, chemotherapy inevitably produces drug resistance, and side effects accompany them. Adjuvant therapy is an effective way to enhance chemotherapeutic drug sensitivity and reduce side effects. This study found allicin, garlic’s active ingredient, is an inhibitor of transmembrane protein 16A (TMEM16A), a novel drug target of lung adenocarcinoma. Allicin concentration-dependently inhibited TMEM16A currents with an IC₅₀ of 24.35 ± 4.14 μM. Allicin thiosulfinate moieties bound with R535A/E624A/E633A residues of TMEM16A blocked the ion transport function and downregulated TMEM16A protein expression affecting the mitogen-activated protein kinase signal transduction. Then, allicin reduced the viability and migration of LA795 cells, and induced cell apoptosis. Moreover, multitarget combination administration results indicated that the therapeutic effect of 3.56 mg/kg allicin and 3 mg/kg cisplatin combined administration was superior to the superposition of the two drugs alone, demonstrating that the anticancer effects of allicin and cisplatin were synergistic. In addition, low-concentration combined administration also avoided the side effects of cisplatin in mice. Based on the good tumor suppressor effect and high biosafety of allicin and cisplatin combination in vivo, allicin can be used for food adjuvant therapy of cisplatin chemotherapy.

更新日期：2022-12-27

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南