Coumarins from the bark of Juglans mandshurica exhibited anti-hepatoma activities via inducing apoptosis

Abstract

Hepatocellular carcinoma (HCC), the most common type of liver cancer, has high morbidity and mortality rates, and its prognosis is poor. The treatment options of HCC are limited by the lack of effective chemotherapy. Therefore, looking for effective drugs with little toxicity is very urgent. The aim of this study was to search for small molecule targeting on liver cancer from Juglans mandshurica, which has been used to treat cancers for a long time in China. Under the guide of anti-hepatoma activity, a new coumarin (1), together with eight reported analogs (2‒9), was isolated from the 75% EtOH extract. The structures of these compounds were determined by 1D and 2D NMR experiments. The absolute configuration of 1 was established by comparison of experimental and calculated electronic circular dichroism (ECD) spectra. The in vitro cytotoxicity experiments on two liver cancer cell lines (HepG2 and Hep3B) showed that compounds 2 and 5 had moderate antitumor activities on both cell lines. And further studies of antitumor mechanisms by the observation of morphological changes and Western blot analyses exhibited that induction of apoptosis might be a possible way that inhibited cell growth.

Keywords:

• Juglandaceae
• Juglans mandshurica
• HCC
• cytotoxicity
• coumarin
• apoptosis