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BBR induces apoptosis in HepG2 cell through an Akt-ASK1-ROS-p38MAPKs-linked cascade.
J Cell Biochem. 2010 Feb 01; 109(2):329-38.JC

Abstract

Berberine (BBR) has indicated significant antimicrobial activity against a variety of organisms including bacteria, viruses, and fungi. The mechanism by which BBR initiates apoptosis remains poorly understood. In the present study, we demonstrated that BBR exhibited significant cytotoxicity in human hepatoma HepG2 cells. Herein, we investigated cytotoxicity mechanism of BBR in HepG2 cells. The results showed that the induction of apoptosis in HepG2 cells by BBR was characterized by DNA fragmentation, an increased percentage of annexin V, and the activation of caspase-3. The expressions of Bcl-2 protein and pro-caspase-3 were reduced by BBR in HepG2 cells. However, Bax protein was increased in the cells. BBR-induced apoptosis was preceded by increased generation of reactive oxygen species (ROS). NAC treatment, a scavenger of ROS, reversed BBR-induced apoptosis effects via inhibition of Bax activation and Bcl-2 inactivation. BBR-induced, dose-dependent induction of apoptosis was accompanied by sustained phosphorylation of MAP Kinases (JNK and p38 MAPK), ASK1, Akt, and p53. Furthermore, SB203580, p38 inhibitor, reduced the apoptotic effect of BBR, and blocks the generation of ROS and NO as well as activation of Bax. We found that the treatment of HepG2 cells with BBR triggers generation of ROS through Akt phosphorylation, resulting in dissociation of the ASK1-mediated activation of JNK and p38 pathways.

Authors+Show Affiliations

Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan 570-749, South Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19950206

Citation

Hyun, Mee-Sun, et al. "BBR Induces Apoptosis in HepG2 Cell Through an Akt-ASK1-ROS-p38MAPKs-linked Cascade." Journal of Cellular Biochemistry, vol. 109, no. 2, 2010, pp. 329-38.
Hyun MS, Hur JM, Mun YJ, et al. BBR induces apoptosis in HepG2 cell through an Akt-ASK1-ROS-p38MAPKs-linked cascade. J Cell Biochem. 2010;109(2):329-38.
Hyun, M. S., Hur, J. M., Mun, Y. J., Kim, D., & Woo, W. H. (2010). BBR induces apoptosis in HepG2 cell through an Akt-ASK1-ROS-p38MAPKs-linked cascade. Journal of Cellular Biochemistry, 109(2), 329-38. https://doi.org/10.1002/jcb.22384
Hyun MS, et al. BBR Induces Apoptosis in HepG2 Cell Through an Akt-ASK1-ROS-p38MAPKs-linked Cascade. J Cell Biochem. 2010 Feb 1;109(2):329-38. PubMed PMID: 19950206.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - BBR induces apoptosis in HepG2 cell through an Akt-ASK1-ROS-p38MAPKs-linked cascade. AU - Hyun,Mee-Sun, AU - Hur,Jung-Mu, AU - Mun,Yeun-Ja, AU - Kim,Dongho, AU - Woo,Won-Hong, PY - 2009/12/2/entrez PY - 2009/12/2/pubmed PY - 2010/8/6/medline SP - 329 EP - 38 JF - Journal of cellular biochemistry JO - J Cell Biochem VL - 109 IS - 2 N2 - Berberine (BBR) has indicated significant antimicrobial activity against a variety of organisms including bacteria, viruses, and fungi. The mechanism by which BBR initiates apoptosis remains poorly understood. In the present study, we demonstrated that BBR exhibited significant cytotoxicity in human hepatoma HepG2 cells. Herein, we investigated cytotoxicity mechanism of BBR in HepG2 cells. The results showed that the induction of apoptosis in HepG2 cells by BBR was characterized by DNA fragmentation, an increased percentage of annexin V, and the activation of caspase-3. The expressions of Bcl-2 protein and pro-caspase-3 were reduced by BBR in HepG2 cells. However, Bax protein was increased in the cells. BBR-induced apoptosis was preceded by increased generation of reactive oxygen species (ROS). NAC treatment, a scavenger of ROS, reversed BBR-induced apoptosis effects via inhibition of Bax activation and Bcl-2 inactivation. BBR-induced, dose-dependent induction of apoptosis was accompanied by sustained phosphorylation of MAP Kinases (JNK and p38 MAPK), ASK1, Akt, and p53. Furthermore, SB203580, p38 inhibitor, reduced the apoptotic effect of BBR, and blocks the generation of ROS and NO as well as activation of Bax. We found that the treatment of HepG2 cells with BBR triggers generation of ROS through Akt phosphorylation, resulting in dissociation of the ASK1-mediated activation of JNK and p38 pathways. SN - 1097-4644 UR - https://www.unboundmedicine.com/medline/citation/19950206/BBR_induces_apoptosis_in_HepG2_cell_through_an_Akt_ASK1_ROS_p38MAPKs_linked_cascade_ L2 - https://doi.org/10.1002/jcb.22384 DB - PRIME DP - Unbound Medicine ER -