BACKGROUND 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. RESULTS 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. CONCLUSIONS 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.

中文翻译：

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补骨脂素通过触发人SMMC7721肝癌细胞中的内质网应激来抑制恶性增殖并诱导凋亡。

背景技术补骨脂素是一种香豆素样且与香豆素有关的苯并呋喃糖苷，是治疗肾脏和脾阳虚证症状的常用中药。据报道补骨脂素显示出类似雌激素的活性，抗氧化剂活性，成骨细胞增殖促进活性，抗肿瘤作用和抗菌活性。然而，补骨脂素的抗肿瘤机制尚未完全了解。本研究旨在探讨补骨脂素在人肝癌细胞SMMC7721中的治疗作用以及抗肿瘤作用的机制。结果补骨脂素以剂量和时间依赖性的方式抑制SMMC7721的增殖，并促进细胞凋亡。此外，补骨脂素激活内质网应激信号通路，包括内质网的扩张，增加了GRP78的mRNA水平，DDIT3，ATF4，XBP1，GADD34以及GDF15，GRP78，IRE1α，XBP-1s的蛋白质水平呈时间依赖性。补骨脂素通过增强CyclinD1和降低CyclinE1表达来诱导G1期细胞周期停滞。而且，TUDC不能抑制补骨脂素诱导的SMMC7721细胞内质网应激。结论补骨脂素可以抑制SMMC7721细胞的增殖并诱导内质网应激反应诱导细胞凋亡，提示补骨脂素可能是预防和治疗肝细胞癌的一种新的治疗方法。