Cytotoxicity and apoptosis induced by a new podophyllotoxin glucoside in human hepatoma (HepG2) cells.
4-Demethylepipodophyllotoxin 7'-O-beta-D-glucopyranoside (4' DPG), a new podophyllotoxin glucoside with a chemical structure similar to that of 4-demethylpicropodophyllotoxin 7'-O-beta-D-glucopyranoside (4DPG), was isolated from the rhizomes of Sinopodophyllum emodi (Wall.) Ying (Berberidaceae). Like 4DPG and etoposide (VP-16), 4' DPG displayed dose- and time-dependent cytotoxic effects in HepG2 cells. Flow cytometric analysis demonstrated the presence of apoptotic cells and DNA fragmentation after HepG2 cells were exposed to 4' DPG (1 micromol/L). In addition, 4' DPG-driven apoptotic events were associated with upregulation of Bax and downregulation of Bcl-2. These results suggest that 4' DPG has prominent cytotoxic activity and induces apoptosis by increasing the ratio of Bax to Bcl-2 in HepG2 cells.
Liu
Yanfeng
Y
Beijing Key Laboratory of Engineered Drug and Biotechnology Laboratory, Beijing 100875, PR China.
Zhao
Changqi
C
Li
Hongxing
H
Yu
Miao
M
Gao
Jiali
J
Wang
Lei
L
Zhai
Yonggong
Y
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis; D016923:Cell Death; D048430:Cell Shape / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005960:Glucosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C440054:4-demethyl-picropodophyllotoxin 7'-O-glucopyranoside; D000972:Antineoplastic Agents, Phytogenic; D005960:Glucosides; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D011034:Podophyllotoxin