Butyrate induces cell apoptosis through activation of JNK MAP kinase pathway in human colon cancer RKO cells |
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Authors: | Yu Zhang Liang Zhou Yong Li Bao Yin Wu Chun Lei Yu Yan Xin Huang Ying Sun Li Hua Zheng Yu Xin Li |
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Institution: | 1. Departments of Medical Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan 336-745, Republic of Korea;2. Department of Biomedical Laboratory Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan 336-745, Republic of Korea;3. Department of Chemistry, College of Natural Sciences, Soonchunhyang University, Asan-Si, Chungnam 336-745, Republic of Korea;1. Department of Anesthesiology, The Maternal and Child Health Hospital of Hunan Province, Changsha, Hunan 410008, China;2. Department of Anesthesiology, The Second Affiliated Hospital of University of South China, Hengyang, Hunan 421001, China |
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Abstract: | Butyrate has been shown to display anti-cancer activity through the induction of apoptosis in various cancer cells. However, the underlying mechanism involved in butyrate-induced apoptosis is still not fully understood. Here, we investigated the cytotoxicity mechanism of butyrate in human colon cancer RKO cells. The results showed that butyrate induced a strong growth inhibitory effect against RKO cells. Butyrate also effectively induced apoptosis in RKO cells, which was characterized by DNA fragmentation, nuclear staining of DAPI, and the activation of caspase-9 and caspase-3. The expression of anti-apoptotic protein Bcl-2 decreased, whereas the apoptotic protein Bax increased in a dose-dependent manner during butyrate-induced apoptosis. Moreover, treatment of RKO cells with butyrate induced a sustained activation of the phosphorylation of c-jun N-terminal kinase (JNK) in a dose- and time-dependent manner, and the pharmacological inhibition of JNK MAPK by SP600125 significantly abolished the butyrate-induced apoptosis in RKO cells. These results suggest that butyrate acts on RKO cells via the JNK but not the p38 pathway. Butyrate triggered the caspase apoptotic pathway, indicated by an enhanced Bax-to-Bcl-2 expression ratio and caspase cascade reaction, which was blocked by SP600125. Taken together, our data indicate that butyrate induces apoptosis through JNK MAPK activation in colon cancer RKO cells. |
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