Flavan enantiomers from Daphne giraldii selectively induce apoptotic cell death in p53-null hepatocarcinoma cells in vitro. (1st June 2018)

• Record Type: Journal Article
• Authors: Yao, Guo-Dong; Sun, Qian; Song, Xiao-Yu; Huang, Xiao-Xiao; Song, Shao-Jiang
• Is Part Of: Chemico-biological interactions. Volume 289(2018)
• Page Start: 1
• Page End: 8
• Publication Date: 2018-06-01
• Subjects: Daphne giraldii -- Flavan enantiomers -- Hepatocellular carcinoma -- Apoptosis -- Reactive oxygen species -- p53; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2018.04.014
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Hepatocellular carcinoma (HCC) is a primary malignant tumor with very poor prognosis. To search for more effective compounds for HCC treatment, two new pairs of flavan enantiomers, daphnegiranol C1 /C2 (1a/1b ) and daphnegiranol D1 /D2 (2a/2b ), were isolated from the stem bark and roots of Daphne giraldii by using chiral chromatography. MTT assay was applied to evaluate their cytotoxicity against three hepatocarcinoma cell lines (Hep3B, MHCC97H, HepG2) as well as a normal liver cell line L02. The results showed that these compounds preferred to inhibit the growth of Hep3B cells (p53 null). Among them, 2a/2b (the IC50 value was 4.87 and 3.35 μM, respectively) exhibited a stronger cytotoxic effect than sorafenib (IC50 = 6.59 μM) in Hep3B cells. A further study demonstrated that2a/2b could induce apoptotic cell death with an increase in reactive oxygen species (ROS) in Hep3B cells. In addition, the IC50 values of2a/2b in HepG2 and MHCC97H cells (both harbored p53 gene) were more than 10-folds greater when compared with Hep3B cells, indicating that2a/2b selectively exhibited cytotoxicity in p53-null hepatocarcinoma cells. Moreover, inhibition of p53 increased the inhibitory effect in p53-wild hepatocarcinoma cells, as well as apoptotic cells and ROS generation. Taken together, flavan enantiomers2a/2b selectively induced apoptosis in Hep3B cells because of p53 deficiency. Highlights: Two new pairs of flavan enantiomers (1a /1b -2a /2b ) were isolated from D. giraldii. 2a /2b had a more cytotoxic effect than sorafenib against Hep3B cells. 2a /2b induced apoptosis and ROS accumulation in Hep3B cells, but not in HepG2 cells. 2a /2b preferred to kill Hep3B cells because of p53 deficiency.