Paeoniae Radix, a Chinese herbal extract, inhibit hepatoma cells growth by inducing apoptosis in a p53 independent pathway.
Paeoniae Radix (PR) is the root of traditional Chinese Herb named Paeonia lactiflora Pallas, which is commonly used to treat liver diseases in China for centuries. Several earlier studies have indicated that PR has anticancer growth activities, however the mechanism underlying these activities was unclear and remained to be elucidated. In this study, we evaluated the molecular mechanism of the effect of PR on human hepatoma cell lines, HepG2 and Hep3B. Our results showed that the water-extract of Paeoniae Radix (PRE) had inhibitory effect on the growth of both HepG2 and Hep3B cell lines. The induction of internucleosomal DNA fragmentation and chromatin condensation appearance, and accumulation of sub-G1 phase of cell cycle profile in PRE treated hepatoma cells evidenced that the cytotoxicity of PRE to the hepatoma cells is through activation of the cell death program, apoptosis. The activation of apoptosis by PRE is independent of the p53 pathway as Hep3B cell is p53-deficient. In addition, the differential gene expression of PRE treated HepG2 was examined by cDNA microarray technology and RT-PCR analysis. We found that the gene expression of BNIP3 was up-regulated while ZK1, RAD23B, and HSPD1 were down-regulated during early apoptosis of the hepatoma cell mediated by PRE. The elucidation of the drug targets of PR on inhibition of tumor cells growth should enable further development of PR for liver cancer therapy.
Lee
Simon Ming Yuen
SM
Department of Biochemistry and The Hong Kong Bioinformatics Center, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.
Li
Mandy Lok Yee
ML
Tse
Yu Chung
YC
Leung
Steve Chin Lung
SC
Lee
Macey Mei Sze
MM
Tsui
Stephen Kwok Wing
SK
Fung
Kwok Pui
KP
Lee
Cheuk Yu
CY
Waye
Mary Miu Yee
MM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D018834:Chaperonin 60 / Q000187:drug effects / Q000235:genetics; D053938:DNA Fragmentation / Q000187:drug effects; D045643:DNA Repair Enzymes; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004365:Drugs, Chinese Herbal; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D029596:Paeonia; D011518:Proto-Oncogene Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
D000970:Antineoplastic Agents; C090121:BNIP3 protein, human; C116838:BNIP3L protein, human; D018834:Chaperonin 60; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D004365:Drugs, Chinese Herbal; D051741:Kruppel-Like Transcription Factors; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; C513287:RAD23B protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C114523:ZNF443 protein, human; C086985:RAD23A protein, human; D045643:DNA Repair Enzymes