Involvement of Bcl-2 family, cytochrome and caspase 3 in induction of apoptosis by beauvericin in human non-small cell lung cancer cells

Lin, Hen‐I; Lee, Yih-Jing; Chen, Bing–Fang; Tsai, Ming-Hsien; Lu, Jen-Lin; Chou, Cheng‐Jen; Jow, Guey–Mei

doi:10.1016/j.canlet.2004.12.044

Cited by 136 publications

(97 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, the complete lack of cellular lactate dehydrogenase release indicative for necrotic cell death emphasizes the apoptotic activity of the anthelmintic drug. These results are comparable to the cytototoxic effects of the structurally related cyclohexadepsipeptides enniatins [31] and beauvericin [32,33]. Moreover, since the ionophoric activity of these cyclic peptides was suggested to contribute to their potent cytotoxicity [33,46,53], comparable modes of actions might be hypothesized for PF1022A.…”

Section: Discussionsupporting

confidence: 66%

“…PF1022A is structurally related to cyclohexadepsipeptides of the enniatin-type for which synergistic effects on antifungal drug activity were described [29,30]. Moreover, potent cytostatic and cytotoxic effects against diverse cancer cell types [31,32,33], antiangiogenic activity [34] as well as anthelmintic properties [35] could be demonstrated for these structurally related cyclohexadepsipeptides.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of the anthelmintic drug PF1022A on mammalian tissue and cells

Dornetshuber¹,

Kamyar²,

Rawnduzi³

et al. 2009

Biochemical Pharmacology

View full text Add to dashboard Cite

Nematode infections cause human morbidity and enormous economic loss in livestock. Since resistance against currently available anthelmintics is a worldwide problem, there is a continuous need for new compounds. The cyclooctadepsipeptide PF1022A is a novel anthelmintic that binds to the latrophilin-like transmembrane receptor important for pharyngeal pumping in nematodes. Furthermore, PF1022A binds to GABA receptors, which might contribute to the anthelmintic effect. Like other cyclodepsipeptides, PF1022A acts as an ionophore. However, no correlation between ionophoric activity and anthelmintic properties was found. This is the first study describing the effect of PF1022A on mammalian cells and tissues. While channel-forming activity was observed already at very low concentrations, changes in intracellular ion concentrations and reduction of contractility in isolated guinea-pig ileum occurred at multiples of anthelmintically active concentrations.PF1022A did not induce necrotic cell death indicated by complete lack of cellular lactate dehydrogenase release. In contrast, apoptosis induction via the mitochondrial pathway was suggested for long-term drug treatment at high concentrations due to numerous apoptotic morphological changes as well as mitochondrial membrane depolarisation. Short time effects were based on cell cycle blockade in G 0 /G 1 phase. Additionally, the cell cycle and apoptosis regulating proteins p53, p21 and bax, but not Bcl-2 were shown to impact on PF1022A-induced cytotoxicity. However, since PF1022A-induced cytotoxicity was found at drug concentrations higher than those used in anthelmintic treatment, it can be suggested that PF1022A intake might not impair human or animal health. Thus, PF1022A seems to be a safe alternative to other anthelmintic drugs.

show abstract

Section: Discussionsupporting

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Effects of the anthelmintic drug PF1022A on mammalian tissue and cells

Dornetshuber¹,

Kamyar²,

Rawnduzi³

et al. 2009

Biochemical Pharmacology

View full text Add to dashboard Cite

show abstract

“…In addition, Bad, a member of the Bcl-2 family that normally binds to the Bcl-2/Bcl-extra larger (Bcl-xL) complex and triggers apoptosis, was significantly increased in this group. p-Bad dissociates from the Bcl-2/Bcl-xL complex, resulting in the suppression of apoptosis (32). However, p-Bad was significantly decreased in the GluA2-siRNA-transfected group compared with the control group in the present study.…”

Section: Discussioncontrasting

confidence: 62%

Knockdown of GluA2 induces apoptosis in non-small-cell lung cancer A549 cells through the p53 signaling pathway

Zhang

Yang

2017

Oncology Letters

View full text Add to dashboard Cite

Abstract. α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are important glutamatergic receptors that mediate fast excitatory synaptic transmission in the brain. Previous studies have demonstrated that glutamate ionotropic receptor AMPA type subunit 2 (GluA2), one of the four subunits that comprise AMPA receptors, is a potential novel marker for poor prognosis in patients with human lung cancer. However, the mechanisms of GluA2-induced apoptosis, proliferation and migration in lung cancer remain unknown. The present study aimed to explore the mechanisms underlying these effects of GluA2 in human lung cancer by silencing GluA2 in A549 cells. Using the Cell Counting Kit-8 assay, western blot analysis and acridine orange/ethidium bromide staining, downregulation of GluA2 was revealed to significantly inhibit the proliferation and significantly promote the apoptosis of A549 cells. Knockdown of GluA2 was also revealed to be associated with increased caspase-3 activity, increased Bcl-2-associated X protein and Bcl-2-associated death promoter (Bad) expression, and decreased expression of B-cell lymphoma-2, p-Bad and X-linked inhibitor of apoptosis protein. In addition, GluA2 silencing upregulated cellular tumor antigen p53 (p53)/p21Cip1/Waf1 /p16 INK4a protein.In conclusion, these results indicate that the effects of GluA2 in lung cancer are mediated by the caspase-3 and p53/p21Cip1/Waf1 /p16 INK4a signaling pathways. Therefore, GluA2 may be a potential novel therapeutic target for the treatment of lung cancer.

show abstract

“…Among the anti-apoptotic members, Bcl-2, Bcl-xl, Bcl-w, Bfl-1, Bag-1, Mcl-1, and A1 are known for protecting against cell death, whereas others, such as Bax, Bak, Blk, Bad, and Bid promote or accelerate cell death. Anti-apoptotic Bcl-2, Bcl-xl and pro-apoptotic Bax, Bak are major members of the Bcl-2 family (Lin et al 2005;Gabriel et al 2003;Hu et al 2012). In this study, the expressions of the pro-apoptosis proteins Bax and Bak were upregulated in the cancer cells, and the expressions of the anti-apoptosis proteins Bcl-2 and Bcl-xl were downregulated by ZJW.…”

Section: Discussionmentioning

confidence: 55%

In vitro anti-proliferative effects of Zuojinwan on eight kinds of human cancer cell lines

et al. 2013

Cytotechnology

View full text Add to dashboard Cite

Zuojinwan (ZJW), a famous Chinese medicinal formula, contains two medicinal herbs Coptis chinese Frach and Evodia rutaecarpa (Juss.) Benth in the ratio of 6: 1. The inhibitory effects of ZJW on eight kinds of human cancer cell lines including SMMC-7721, BEL-7402, BEL-7404, HepG2, A549, NCI-H446, NCI-H460 and HCT-116 cells were evaluated, and the possible mechanism was investigated. The growths of the eight kinds of cancer cells were inhibited by ZJW assessed through MTT assay. Flow cytometry assay revealed a sub-G1 peak with reduced DNA content was formed. The cell cycle was arrested in the G0/G1 phase in ZJW-treated SMMC-7721 and HepG2 cells, and in the S phase for NCI-H460 cells. Significant DNA damage was produced by ZJW assessed with single-cell gel electrophoresis assay. Morphological changes were also observed. Caspase-3 and -9 activities were increased following ZJW treatment. Western blot analysis showed that Bax and Bak protein levels were increased after ZJW treatment, while Bcl-2 and Bcl-xl protein levels were decreased. Our results suggest that ZJW has significant anti-cancer activities due to induction of mitochondria-dependent apoptosis pathway. Therefore, ZJW has the potential to be a novel chemotherapy drug to treat hepatoma, lung cancer and colon cancer by suppressing tumor growth.

show abstract

Involvement of Bcl-2 family, cytochrome and caspase 3 in induction of apoptosis by beauvericin in human non-small cell lung cancer cells

Cited by 136 publications

References 32 publications

Effects of the anthelmintic drug PF1022A on mammalian tissue and cells

Effects of the anthelmintic drug PF1022A on mammalian tissue and cells

Knockdown of GluA2 induces apoptosis in non-small-cell lung cancer A549 cells through the p53 signaling pathway

In vitro anti-proliferative effects of Zuojinwan on eight kinds of human cancer cell lines

Contact Info

Product

Resources

About