Artesunate enhances radiosensitivity of human non-small cell lung cancer A549 cells via increasing NO production to induce cell cycle arrest at G2/M phase

Zhao, Yanyan; Jiang, Weiwei; Li, Bin; Yao, Qi; Dong, Jun-Qing; Cen, Yanyan; Pan, Xichun; Li, Jun; Zheng, Jie; Pang, Xiaowu; Zhou, Hong

doi:10.1016/j.intimp.2011.08.017

Cited by 69 publications

(49 citation statements)

References 41 publications

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“…[29][30][31][32][33] In the present study, we demonstrate that PLK1 inhibition with BI 2536 causes mitotic arrest in GBM cell lines, and that pretreatment with this drug efficiently sensitizes cells to radiation by decreasing proliferation and self-renewal in all the cell lines tested. Decreased proliferation after treatment with BI 2536 alone has already been demonstrated in different tumors: cervix adenocarcinoma, 24 leukemia, 34 anaplastic thyroid carcinoma, 35 melanomas, 15 and osteosarcoma cells.…”

Section: Pezuk Et Alsupporting

confidence: 56%

Inhibition of Polo-Like Kinase 1 Induces Cell Cycle Arrest and Sensitizes Glioblastoma Cells to Ionizing Radiation

Pezuk

Brassesco

Morales

et al. 2013

Cancer Biotherapy and Radiopharmaceuticals

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Despite efforts to improve surgical, radiologic, and chemotherapeutic strategies, the outcome of patients with glioblastoma (GBM) is still poor. Polo-like kinase 1 (PLK1) is a serine/threonine kinase that plays key roles in cell cycle control and has been associated with tumor growth and prognosis. Here, we aimed at testing the radiosensitizing effects of the PLK1 inhibitor BI 2536 on eight GBM cell lines. For cell cycle analysis, T98G, U251, U343 MG-a, LN319, SF188, U138 MG, and U87 MG cell lines were treated with 10, 50, or 100 nM of BI 2536 for 24 hours. In addition, cell cultures exposed to BI 2536 50 nM for 24 hours were irradiated with c-rays from 60 Cobalt source at final doses of 2, 4, and 6 Gy. Combinatorial effects were evaluated through proliferation and clonogenic capacity assays. Treatment with BI 2536 caused mitotic arrest after 24 hours, and increased apoptosis in GBM cells. Moreover, our results demonstrate that pretreatment with this drug sensitized six out of seven GBM cell lines to different doses of c-irradiation as shown by decreased growth and abrogation of colony-formation capacity. Our data suggest that PLK1 blockage has a radiosensitizing effect on GBM, which could improve treatment strategies for this devastating tumor.

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Section: Pezuk Et Alsupporting

confidence: 56%

Inhibition of Polo-Like Kinase 1 Induces Cell Cycle Arrest and Sensitizes Glioblastoma Cells to Ionizing Radiation

Pezuk

Brassesco

Morales

et al. 2013

Cancer Biotherapy and Radiopharmaceuticals

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“…For instance, ART has been shown to induce apoptosis and necrosis in multiple human cancer cells (4,5). The anti-cancer effects of ART also include the following: cell cycle arrest (6), inhibition of angiogenesis (7), and reduction of cell invasion and metastasis (8). Moreover, the anti-cancer potential of ART has also been tested in a number of animal cancer models (4,6,9).…”

mentioning

confidence: 99%

“…The anti-cancer effects of ART also include the following: cell cycle arrest (6), inhibition of angiogenesis (7), and reduction of cell invasion and metastasis (8). Moreover, the anti-cancer potential of ART has also been tested in a number of animal cancer models (4,6,9). However, the exact mechanisms underlying ART-mediated cell death have not been fully elucidated.…”

mentioning

confidence: 99%

Artesunate Induces Cell Death in Human Cancer Cells via Enhancing Lysosomal Function and Lysosomal Degradation of Ferritin

Yang

Tan

et al. 2014

Journal of Biological Chemistry

142

110

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Background: Artesunate is capable of inducing cell death in cancer cells. Results: Artesunate accumulates in lysosomes and promotes lysosomal function and ferritin degradation, leading to mitochondrial reactive oxygen species production and eventually cell death. Conclusion: Intracellular iron and ferritin degradation is essential for artesunate-induced lysosomal activation and cell death. Significance: This work reveals a novel mechanism underlying artesunate-induced cell death.

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“…Of these drugs, there are many FDA-approved compounds currently used clinically for the treatment of NSCLC including paclitaxel (Jinhyang 2012) and cisplatin (Zhang 2011). In addition, there are many drugs under investigation for the treatment of NSCLC such as imatinib (Zhang 2003), everolimus (Kochanski 2012), and artesunate (Zhao 2011). While these particular drugs are not yet widely used in the treatment of NSCLC, they are currently approved for the treatment of other types of cancer.…”

Section: Background and Treatment Of Lung Cancermentioning

confidence: 99%

Tumor-penetrating acetalated dextran nanoparticles capable of tandem delivery of agents for the treatment of lung cancer

Sun

Meenach

2014

2014 40th Annual Northeast Bioengineering Conference (NEBEC)

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The overall survival rate for patients diagnosed with lung cancer is still extremely low and many affected patients are not eligible for first-line treatments such as surgery, chemotherapy, and radiation for the treatment due to the severe side effects associated with these therapies. Paclitaxel (PTX) along with imatinib mesylate are currently first-line therapies for many types of cancer (Kelly 2001, Schiller 2002.However, the successful delivery of paclitaxel faces many challenges due to its lipophilic nature and high protein affinity, which often results in low bioavailability. While the enhanced permeability and retention (EPR) effect has served as a key rationale for using nanoparticles to treat solid tumors, as it allows for increased uptake of NPs at the tumor site, it often does not enable uniform delivery of these particles to all regions of tumors. Tumor-penetrating peptides show great promise in overcoming the relevant physiological barriers preventing accumulation and penetrating into the avascular region of tumors. iRGD (internalizing RGD, CRGDKDPDC), has been shown to effectively target and penetrate both in vitro multicellular spheroids (MCS) and in vivo animal model tumors when conjugated to drugs or nanoparticles (Sugahara 2010). For the described research, I hypothesize that iRGD-conjugated nanoparticles containing PTX and imatinib will more effectively home to and penetrate lung cancer tumor spheroids for more effective treatment of this dismal disease.In particular, acetalated dextran (Ac-Dex) nanoparticles were synthesized to contain PTX and/or imatinib. These particles were shown to have sizes appropriate for systemic delivery (approximately 250 nm) and exhibited smooth, round morphology.All particle systems exhibited favorable homogeneity as evidenced by low polydispersity index values (less than 0.20) and were nearly neutral in charge with zeta potentials near zero. Both PTX and imatinib were successfully loaded into the nanoparticles with 50 and 14 weight % loading, respectively. 80% of iRGD was conjugated to the nanoparticles and the peptide showed affinity for A549 lung adenocarcinoma cells in vitro. A549 multicellular spheroids were generated to allow for evaluation of the newly developed therapeutics. Finally, in vitro analysis using A549 cells showed that the drug-loaded nanoparticles were more effective at killing cells than pure drugs. Overall, this work shows the promise of Ac-Dex drug-loaded nanoparticles conjugated with iRGD to enhance the treatment of lung cancer.iv ACKNOWLEDGMENTS

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Artesunate enhances radiosensitivity of human non-small cell lung cancer A549 cells via increasing NO production to induce cell cycle arrest at G2/M phase

Cited by 69 publications

References 41 publications

Inhibition of Polo-Like Kinase 1 Induces Cell Cycle Arrest and Sensitizes Glioblastoma Cells to Ionizing Radiation

Inhibition of Polo-Like Kinase 1 Induces Cell Cycle Arrest and Sensitizes Glioblastoma Cells to Ionizing Radiation

Artesunate Induces Cell Death in Human Cancer Cells via Enhancing Lysosomal Function and Lysosomal Degradation of Ferritin

Tumor-penetrating acetalated dextran nanoparticles capable of tandem delivery of agents for the treatment of lung cancer

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