"Thus, CsBCL-2 can be considered as multidomain, containing anti-apoptotic BCL-2 member (Lee et al., 2013). Moreover, the presence of BH4 domain in the CsBCL-2 protein ensures that it is an anti-apoptotic protein (Antonsson and Martinou, 2000). Feng and Rise (2010) observed a PEST region in Atlantic cod MCL-1 protein , an anti-apoptotic BCL-2 like gene at 82–179. "
[Show abstract][Hide abstract] ABSTRACT: B-cell lymphoma-2 (BCL-2) is a suppressor of apoptosis and inhibits the caspase dependent apoptosis pathway. In this study, we report molecular characterization of a cDNA sequence encoded of BCL-2 from striped murrel, Channa striatus. A partial cDNA sequence of CsBCL-2 was identified from the striped murrel cDNA library during annotation. Subsequently, the full length CsBCL-2 cDNA sequence was obtained by an internal sequencing method using a forward primer. The sequence contains 699 nucleotide base pairs which encode 232 amino acid residues. The domain and motif analysis revealed that the CsBCL-2 polypeptide consists of BCL-2 homologous domain BH4 at the N-terminal region between 4 and 21 and the BCL-2 homologous domains BH1, BH2 and BH3 between 87 and 187. The CsBCL-2 polypeptide sequence does not have a signal peptide region, but it consists of two novel transmembrane regions at 134–152 and 209–226. The sequence analysis showed that the CsBCL-2 has highest sequence identity (70%) with BCL-2 like protein 1 (BCL-2 L1) from pufferfish Takifugu rubripes. The phylogenetic analysis showed that the CsBCL-2 was situated in the BCL-2 L1 fish clade. The secondary analysis showed that the CsBCL-2 protein consists of 132 amino acid residues in the α-helical region and 100 amino acid residues in the random coil region. The validated 3D structure of CsBCL-2 showed the active residues Gly135 and Arg136 in the 7th α-helical position, whereas Trp178 is in the 9th α-helical region. CsBCL-2 mRNA transcription is predominately present in spleen and is upregulated upon being induced with fungus Aphanomyces invadans, bacteria Aeromonas hydrophila, Escherichia coli LPS, Laminaria digitata beta-1,3-glucan and poly I:C. Overall, the CsBCL-2 mRNA transcription results indicate the potential involvement of CsBCL-2 in immune system of C. striatus. However, further research at proteomic level is necessary to examine these predictions.
"Pro-and anti-apoptotic members of the Bcl-2 family gather at the surface of mitochondria , where they compete to regulate cytochrome c release. Members of the Bcl-2 family are characterized by one or more conserved Bcl-2 homology (BH) domains and have been classified into three functional groups: members of group I, such as Bcl-2, possess anti-apoptotic activity, while members of group II, such as Bax and Bak, are pro-apoptotic; group III consists of diverse proteins whose only common feature is the presence of the BH3 domain    . In the event of apoptosis, cytochrome c is released from mitochondria, associates with Apaf-1 and caspase-9, leading eventually to the activation of caspase-9   . "
"Apoptosis, which is characterized by cytoplasmic shrinkage, chromatin condensation and DNA fragmentation, is an active form of cell death that occurs in response to several agents, including anticancer chemotherapeutic drugs (Lawen et al., 2003). Many biomarkers and events, such as the caspase family proteins and Bcl-2 family members, could be considered as the determinants of apoptosis (Antonsson et al., 2000). The abnormal production of the molecule may trigger redox signaling pathways, such as oxidative stress, cell cycle arrest and apoptosis (Zhang et al., 2013). "
[Show abstract][Hide abstract] ABSTRACT: THis study was conducted to analyze the molecular mechanisms responsible for anti-proliferation effects of glaucocalyxin A in cultured MCF-7 and Hs578T breast cancer cells. The concentration that reduced cell viability to 50% (IC50) after 72 h treatment was derived and potential molecular mechanisms of anti-proliferation using the IC50 were investigated as changes in cell cycle arrest and apoptosis. Gene and protein expression changes related to apoptosis were investigated by semi-quantitative RT-PCR and western blotting, respectively. Involvement of phosphorylated mitogen-activated protein kinases and JNK signaling in regulation of these molecules was characterized by western blotting. Cell viability decreased in a concentration-dependent manner and the IC50 was determined as 1 μM in MCF-7 and 4 μM in Hs578T cell. Subsequently, we demonstrated that the GLA-induced MCF-7 and Hst578T cell death was due to cell cycle arrest at the G2/M transition and was associated with activation of the c-jun N-terminal kinase (JNK) pathway. We conclude that GLA has the potential to inhibit the proliferation of human breast cancer cells through the JNK pathway and suggest its application forthe effective therapy for patients with breast cancer.
Asian Pacific journal of cancer prevention: APJCP 10/2013; 14(10):5805-10. DOI:10.7314/APJCP.2013.14.10.5805 · 2.51 Impact Factor
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