Ionizing Radiation Potentiates Dihydroartemisinin-Induced Apoptosis of A549 Cells via a Caspase-8-Dependent Pathway

Chen, Tongsheng; Chen, Min; Chen, Jingqin

doi:10.1371/journal.pone.0059827

Cited by 25 publications

(28 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5e), corroborating the dominant role of Bak in DHA-induced intrinsic apoptosis in HCC cells [27]. In contrast, the Bax-mediated intrinsic pathway has been reported to play a key role in DHAinduced apoptosis in various cell lines [13,[18][19][20][21][22][23][24]. Therefore, the pro-apoptotic action of DHA is cell typedependent.…”

Section: Discussionmentioning

confidence: 54%

“…Accumulated proofs have shown the important role of the Bax-dependent intrinsic apoptosis pathway in DHA-induced apoptosis of multiple types of cancer cells [15,[18][19][20][21][22]. Our recent studies also demonstrated that the Bax-mediated intrinsic apoptosis pathway played a dominant role in DHA-induced apoptosis of lung cancer cells [20,23,24], while the Bak-mediated intrinsic apoptosis pathway controlled the pro-apoptotic actions of the combined treatment with DHA and gemcitabine in inducing apoptosis of A549 cells [13]. Moreover, Bak but not Bax has also been demonstrated to be the key regulator to trigger the intrinsic apoptosis pathway in DHA-induced apoptosis of Jurkat T-lymphoma cells [25].…”

Section: Introductionmentioning

confidence: 66%

“…Puma was reported to be up-regulated in DHA-induced apoptosis in melanoma and colon cancer cells [33,34]. In human lung cancer cells, our recent studies found that Bid was not involved in ART-induced apoptosis [35] but might be involved in DHA-induced apoptosis [13,24]. Recently, Zhang and coworkers found that Bid was not involved in DHA-induced apoptosis of HCC cells [27].…”

Section: Introductionmentioning

confidence: 97%

See 2 more Smart Citations

Dihydroartemisinin induces apoptosis preferentially via a Bim-mediated intrinsic pathway in hepatocarcinoma cells

et al. 2015

Self Cite

View full text Add to dashboard Cite

This report is designed to dissect the detail molecular mechanism by which dihydroartemisinin (DHA), a derivative of artemisinin, induces apoptosis in human hepatocellular carcinoma (HCC) cells. DHA induced a loss of the mitochondrial transmemberane potential (ΔΨm), release of cytochrome c, activation of caspases, and externalization of phosphatidylserine indicative of apoptosis induction. Compared with the modest inhibitory effects of silencing Bax, silencing Bak largely prevented DHA-induced ΔΨm collapse and apoptosis though DHA induced a commensurable activation of Bax and Bak, demonstrating a key role of the Bak-mediated intrinsic apoptosis pathway. DHA did not induce Bid cleavage and translocation from cytoplasm to mitochondria and had little effects on the expressions of Puma and Noxa, but did increase Bim and Bak expressions and decrease Mcl-1 expression. Furthermore, the cytotoxicity of DHA was remarkably reduced by silencing Bim, and modestly but significantly reduced by silencing Puma or Noxa. Silencing Bim or Noxa preferentially reduced DHA-induced Bak activation, while silencing Puma preferentially reduced DHA-induced Bax activation, demonstrating that Bim and to a lesser extent Noxa act as upstream mediators to trigger the Bak-mediated intrinsic apoptosis pathway. In addition, silencing Mcl-1 enhanced DHA-induced Bak activation and apoptosis. Taken together, our data demonstrate a crucial role of Bim in preferentially regulating the Bak/Mcl-1 rheostat to mediate DHA-induced apoptosis in HCC cells.

show abstract

Section: Discussionmentioning

confidence: 54%

Section: Introductionmentioning

confidence: 66%

Section: Introductionmentioning

confidence: 97%

See 1 more Smart Citation

Dihydroartemisinin induces apoptosis preferentially via a Bim-mediated intrinsic pathway in hepatocarcinoma cells

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…DHA has been reported that have co-treatment effect with many other anti-tumor compounds (Caia et al, 2004;Zongo et al, 2007;Chen et al, 2013). After enrolled into cytosol, DHA can react with Fe 2+ to generate a lot of reactive oxygen species which mediated caspase-9, -3 and/ or caspase-8 activation resulting in cell apoptosis (Mercer et al, 2007;Mercer et al, 2011).…”

Section: 5895 Dihydroartemisinine Enhances Dictamnine-induced Apoptomentioning

confidence: 99%

Dihydroartemisinine Enhances Dictamnine-induced Apoptosis via a Caspase Dependent Pathway in Human Lung Adenocarcinoma A549 Cells

An¹,

Liu²,

Zhang³

et al. 2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Dictamnine (Dic) has the ability to exert cytotoxicity in human cervix, colon, and oral carcinoma cells and dihydroartemisinin (DHA) also has potent anticancer activity on various tumour cell lines. This report explores the molecular mechanisms by which Dic treatment and combination treatment with DHA and Dic cause apoptosis in human lung adenocarcinoma A549 cells. Dic treatment induced concentration-and time-dependent cell death. FCM analysis showed that Dic induced S phase cell cycle arrest at low concentration and cell apoptosis at high concentration in which loss of mitochondrial membrane potential (ΔΨm) was not involved. In addition, inhibition of caspase-3 using the specific inhibitor, z-DQMD-fmk, did not attenuate Dic-induced apoptosis, implying that Dic-induced caspase-3-independent apoptosis. Combination treatment with DHA and Dic dramatically increased the apoptotic cell death compared to Dic alone. Interestingly, pretreatment with z-DQMD-fmk significantly attenuated DHA and Dic co-induced apoptosis, implying that caspase-3 plays an important role in Dic and DHA co-induced cell apoptosis. Collectively, we found that Dic induced S phase cell cycle arrest at low concentration and cell apoptosis at high concentration in which mitochondria and caspase were not involved and DHA enhanced Dic induced A549 cell apoptosis via a caspase-dependent pathway.

show abstract

“…The metabolism and detoxification of xenobiotics performed by cytochrome P450 may be associated with SPN metabolism and ROS generation [36]. Therefore, the present study suggests that ROS production on A549 cells may be associated with cell death and inhibition of proliferation, as evidenced by Chen et al (2013) [37].…”

Section: Oxidative Stress In A549 Cellsmentioning

confidence: 73%

PVM/MA-shelled selol nanocapsules promote cell cycle arrest in A549 lung adenocarcinoma cells

Souza

Muehlmann

Santos

et al. 2014

Journal of Nanobiotechnology

View full text Add to dashboard Cite

Background: Selol is an oily mixture of selenitetriacylglycerides that was obtained as a semi-synthetic compound containing selenite. Selol is effective against cancerous cells and less toxic to normal cells compared with inorganic forms of selenite. However, Selol's hydrophobicity hinders its administration in vivo. Therefore, the present study aimed to produce a formulation of Selol nanocapsules (SPN) and to test its effectiveness against pulmonary adenocarcinoma cells (A549).

show abstract

Ionizing Radiation Potentiates Dihydroartemisinin-Induced Apoptosis of A549 Cells via a Caspase-8-Dependent Pathway

Cited by 25 publications

References 24 publications

Dihydroartemisinin induces apoptosis preferentially via a Bim-mediated intrinsic pathway in hepatocarcinoma cells

Dihydroartemisinin induces apoptosis preferentially via a Bim-mediated intrinsic pathway in hepatocarcinoma cells

Dihydroartemisinine Enhances Dictamnine-induced Apoptosis via a Caspase Dependent Pathway in Human Lung Adenocarcinoma A549 Cells

PVM/MA-shelled selol nanocapsules promote cell cycle arrest in A549 lung adenocarcinoma cells

Contact Info

Product

Resources

About