Abstract

BackgroundPsoralen 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.ResultsPsoralen 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.ConclusionsPsoralen 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.

Highlights

  • 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 inhibits the proliferation of SMMC7721 cells We first examined whether psoralen was cytotoxic to hepatoma cell lines

  • Compared with the control group, the SMMC7721 cells treated with different dose psoralens for 24 h, 48 h and 72 h

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Summary

Introduction

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. This study aimed to investigate the therapeutic efficacy of psoralen in human hepatoma cell line SMMC7721 and the mechanism of antitumor effects. Hepatocellular carcinoma (HCC) is one of the most common malignant cancer worldwide and the second leading cause of cancer death for male in China, especially in China’s rural areas, and it is considered as the sixth leading cause of cancer-related mortality for male in developed countries. Screening effective anti-hepatoma drugs from traditional Chinese medicine herbs is a necessary research field. Some effective ingredients of Chinese medicinal herbs, such as icariin, psoralen, osthole, matrine, ginsenoside Rg1/Rh2 and celastrol, were reported to inhibit the proliferation of hepatocellular

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