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CR‐108, a novel vitamin K derivative induces apoptosis through ROS and mitochondrial dysfunction in breast cancer
Author(s) -
Chao Jui I,
Yang Chun-Ru,
Chen Chinpiao
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb236
Subject(s) - survivin , apoptosis , reactive oxygen species , mitochondrion , p38 mitogen activated protein kinases , mitochondrial ros , cancer cell , protein kinase a , cancer research , kinase , chemistry , cytochrome c , microbiology and biotechnology , biology , cancer , biochemistry , genetics
Vitamin K derivatives exert anticancer activities. Here, we found a novel vitamin K derivative, CR‐108, which induced apoptosis in human breast cancer cells. CR‐108 reduced the cell viability in both the non‐HER‐2‐overexpressed MCF‐7 and HER‐2‐ overexpressed BT‐474 breast cancer cells. Interestingly, CR‐108 highly elicited the intracellular reactive oxygen species (ROS) in breast cancer cells. CR‐108 markedly induced the loss of mitochondrial membrane potential analyzed by fluorescence intensities of JC‐1 and DiOC6. Moreover, CR‐108 induced cytochrome c release from mitochondria to cytosol, elevated the levels of cleaved PARP proteins, and increased apoptotic induction. A ROS scavenger NAC completely blocked the CR‐ 108‐induced ROS, mitochondrial damage, and apoptosis. Meantime, CR‐108 increased the phosphorylated p38 kinase but conversely inhibited the survivin protein expression. NAC prevented the activation of p38 kinase and restored the survivin protein levels. In addition, a specific p38 kinase inhibitor SB202190 reduced the survivin protein level and attenuated the CR‐108‐induced cytotoxicity. Taken together, CR‐108 induces apoptosis through ROS and mitochondrial damage pathway associated with p38 kinase and survivin in the human breast cancer.