Benzo(a)pyrene-induced apoptotic death of mouse hepatoma Hepa1c1c7 cells via activation of intrinsic caspase cascade and mitochondrial dysfunction.
Benzo(a)pyrene (BaP), a potent carcinogen, has been shown to induce apoptosis via activation of caspase-3. However, the upstream of caspase-3 and other apoptosis signaling remain to be elusive. Herein, we demonstrated that treatment of Hepa1c1c7 cells with BaP increased the transcriptional expression of aryl hydrocarbon nuclear transporter and cytochrome p450 1A1 in a time and dose-dependent manner but did not aromatic hydrocarbon receptor. Also, the catalytic activation of caspase-3 and caspase-9 was induced whereas that of caspase-3 and caspase-9 was not by the addition of BaP. BaP also induced the mitochondrial dysfunction, including transition of mitochondria membrane potential and cytosolic release of cytochrome c. Furthermore, a decrease in the expression of Bcl-2 to Bax ratio and phosphorylation of p53(Ser 15) were observed in BaP-treated cells. Taken together, these results demonstrated that BaP-induced apoptosis of Hepa1c1c7 cells via activation of intrinsic caspase pathway including caspase-3, caspase-9, with mitochondrial dysfunction and p53 activation.
Ko
Chang-Bo
CB
Vestibulocochlear Research Center and Department of Microbiology, Wonkwang University School of Medicine, 344-2 Shinyong-dong, Iksan, Jeonbuk 570-749, South Korea.
Kim
Se-Jin
SJ
Park
Channy
C
Kim
Bok-Ryang
BR
Shin
Chang-Ho
CH
Choi
Sujinna
S
Chung
Sang-Young
SY
Noh
Joon-Hwa
JH
Jeun
Jin-Ho
JH
Kim
Nam-Song
NS
Park
Raekil
R
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001564:Benzo(a)pyrene / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000378:metabolism; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D002273:Carcinogens; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D001564:Benzo(a)pyrene; D020169:Caspases