Basic Medical School of Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203, China.
Biol Res. 2019 Jul 5;52(1):34. doi: 10.1186/s40659-019-0241-8.
Psoralen is a coumarin-like and coumarin-related benzofuran glycoside, which is a commonly used traditional Chinese medicine to treat patients with kidney and spleen-yang deficiency symptom. Psoralen has been reported to show estrogen-like activity, antioxidant activity, osteoblastic proliferation accelerating activity, antitumor effects and antibacterial activity. However, the antitumor mechanism of psoralen is not fully understood. This study aimed to investigate the therapeutic efficacy of psoralen in human hepatoma cell line SMMC7721 and the mechanism of antitumor effects.
Psoralen inhibited proliferation of SMMC7721 in a dose- and time-dependent manner, and promoted apoptosis. Further, psoralen activated the ER stress signal pathway, including the expansion of endoplasmic reticulum, increasing the mRNA levels of GRP78, DDIT3, ATF4, XBP1, GADD34 and the protein levels of GDF15, GRP78, IRE1α, XBP-1s in a time-dependent manner. Psoralen induces cell cycle arrest at G1 phase by enhancing CyclinD1 and reducing CyclinE1 expression. Moreover, TUDC couldn't inhibit the psoralen-induced ER stress in SMMC7721 cells.
Psoralen can inhibit the proliferation of SMMC7721 cells and induce ER stress response to induce cell apoptosis, suggesting that psoralen may represent a novel therapeutic option for the prevention and treatment hepatocellular carcinoma.
补骨脂素是香豆素类和呋喃香豆素类苯并呋喃糖苷，是一种常用的治疗脾肾阳虚证的中药。补骨脂素具有类雌激素活性、抗氧化活性、促进成骨细胞增殖活性、抗肿瘤作用和抗菌活性。然而，补骨脂素的抗肿瘤机制尚不完全清楚。本研究旨在探讨补骨脂素对人肝癌细胞株 SMMC7721 的治疗作用及其抗肿瘤作用机制。
补骨脂素呈剂量和时间依赖性抑制 SMMC7721 细胞增殖，并促进细胞凋亡。此外，补骨脂素通过增强内质网扩张，增加 GRP78、DDIT3、ATF4、XBP1、GADD34 的 mRNA 水平和 GDF15、GRP78、IRE1α、XBP-1s 的蛋白水平，在时间依赖性方式激活内质网应激信号通路。补骨脂素通过增强 CyclinD1 表达和降低 CyclinE1 表达使细胞周期阻滞在 G1 期。此外，TUDC 不能抑制补骨脂素诱导的 SMMC7721 细胞内质网应激。
补骨脂素能抑制 SMMC7721 细胞增殖，并诱导内质网应激反应诱导细胞凋亡，提示补骨脂素可能为预防和治疗肝细胞癌提供新的治疗选择。
