Dracorhodin perchlorate induces A375-S2 cell apoptosis via accumulation of p53 and activation of caspases.
Dracorhodin perchlorate, an anthocyanin red pigment, induces human melanoma A375-S2 cell death through the apoptotic pathway. Caspase-3, -8, -9, and -10 inhibitors partially reversed the cell death induced by dracorhodin perchlorate. Caspase-3 and -8 were activated, followed by the degradation of caspase-3 substrates, the inhibitor of caspase-activated DNase, and poly-(ADP-ribose) polymerase. Dracorhodin perchlorate upregulated the expression ratio of Bax/Bcl-2 and significantly increased the expression of p53 and p21(WAF1) proteins. The cell death was partially reduced by the mitogen-activated protein kinase c-JUN NH2-terminal protein kinase (JNK MAPK) inhibitor (SP600125) and p38 MAPK inhibitor (SB 203580), while the MEK inhibitor (PD98059) augmented cell death; the drug induced sustained phosphorylation of JNK and p38 MAPK. Moreover, the Fas agonistic antibody CH-11 has a synergistic effect with dracorhodin perchlorate. The phoshatidylinositol 3-kinase (PI3-K) family inhibitor wortmanin and tyrosine kinase inhibitor genistein rescued the viability loss induced by dracohodin perchlorate. Taken together, dracorhodin perchlorate induces apoptosis in A375-S2 cells via accumulation of p53, alters the Bax/Bcl-2 ratio, and activates caspases and p38/JNK MAPKs.
Xia
Mingyu
M
China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, China.
Wang
Minwei
M
Tashiro
Shin-ichi
S
Onodera
Satoshi
S
Minami
Mutsuhiko
M
Ikejima
Takashi
T
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D016158:Genes, p53 / Q000187:drug effects* / Q000502:physiology; D006801:Humans
D001578:Benzopyrans; C060327:dracorhodin; D020169:Caspases