ATP production, induction of cell cycle arrest, autophagy, and apoptotic processes through activation of adenosine-5’-monophosphate-activated protein kinase (AMPK) 5 and inhibition of the mTOR (mammalian target of rapamycin) pathway in glioblastoma cells. 6 , 7 AMPK is a serine/threonine kinase that functions as a cellular energy sensor. AMPK is an obligate heterotrimer, consisting of one catalytic subunit (α) and two regulatory subunits (β and γ). 8 Under cellular stress conditions, AMPK is activated by increased AMP-to-ATP ratios to promote catabolism and
Sebastian Adeberg, Denise Bernhardt, Semi B. Harrabi, Nils H. Nicolay, Juliane Hörner-Rieber, Laila König, Michael Repka, Angela Mohr, Amir Abdollahi, Klaus-Josef Weber, Juergen Debus and Stefan Rieken
Ruxandra Irimia, Ioana Teodora Tofolean, Roxana Gabriela Sandu, Oana Elena Băran, Maria Cătălina Ceauşescu, Vlad Coşoreanu, Maria Teodora Ilie, Ramona Babeş, Constanţa Ganea and Irina Băran
Doxorubicin is a widely used chemotherapeutic drug, effective on patients with acute lymphoblastic leukemia but associated with significant long term cardio-toxicity. Menadione (vitamine K3) and the flavonoid quercetin are known as strong apoptogens in human leukemia Jurkat T cells.
We explored the potential synergic cytotoxic effects of doxorubicin in association with quercetin and Menadione in this cellular model for acute lymphoblastic leukemia.
Cellular viability, apoptosis, necrosis oxidative stress and cellular cycle were determined by flow cytometry utilizing Jurkat lymphoblasts labeled with Annexin V-FITC/7-AAD, CM-H2DCFDA/7-AAD and propidium iodide respectively.
Results indicate a dose-dependent oxidative-stress generation, cell cycle arrest and apoptosis induction by doxorubicin alone, correlated with a decrease of the required doses when the anticancer drug was associated with quercetin and menadione, hence supporting the theory of an additive cytotoxic effect on leukemia cells.
Introducing QC-MD combinations in leukemia doxorubicin-based treatment could significantly increase the treatment’s efficacy. The main mechanism responsible for this effect appears to be the increase in DOX affinity for DNA, which enables lowering of the therapeutic dose.
Jakob Liermann, Patrick Naumann, Franco Fortunato, Thomas E. Schmid, Klaus-Josef Weber, Jürgen Debus and Stephanie E. Combs
ponicidin have been published. 6 , 7 , 8 In pancreatic cancer oridonin induces apoptosis and leads to an arrest in the G2/M-phase of the cell cycle. 9 , 10 , 11 , 12 Further, oridonin inhibits nuclear factor-kB. 13 Ponicidin is also known to induce apoptosis 14 , 15 , 16 , 17 but to our knowledge, there is no data for ponicidin in pancreatic cancer. Potential radiosensitization could be observed in chinese-hamster-V79 cells by oridonin. 18 Apart from this study we found no publication concerning oridonin or ponicidin induced radiomodulation. As natural occurring
Xinyu Wu, Daixing Zhong, Bin Lin, Wenliang Zhai, Zhenqi Ding and Jin Wu
correlation with BRAF V600E and different KRAS mutations in metastatic colorectal cancer - a single institution retrospective analysis. Radiol Oncol 2011; 45: 285-91. 25. Bulavin DV, Kovalsky O, Hollander MC, Fornace AJ Jr. Loss of oncogenic H-ras-induced cell cycle arrest and p38 mitogen-activated protein kinase activation by disruption of Gadd45a. Mol Cell Biol 2003; 23: 3859-71. 26. Cardaci S, Filomeni G, Rotilio G, Ciriolo MR. p38(MAPK)/p53 signalling axis mediates neuronal apoptosis in response to tetrahydrobiopterin
Valerija Zager, Maja Cemazar, Irena Hreljac, Tamara Lah, Gregor Sersa and Metka Filipic
genotoxins. Mutat Res-Gen Tox En 2008; 653 : 63-9. Zhou B-BS, Elledge SJ. The DNA damage response: putting checkpoints in perspective. Nature 2000; 408 : 433-9. Sionov RV, Haupt Y. The cellular response to p53: the decision between life and death. Oncogene 1999; 18 : 6145-57. Waldman T, Kinzler KW, Vogelstein B. P21 is necessary for the P53-mediated G1 arrest in human cancer cells. Cancer Res 1995; 55 : 5187-90. Vogelstein B, Lane D, Levine AJ. Surfing the p
Ivana Steiner, Nikolina Stojanovic, Aljosa Bolje, Anamaria Brozovic, Denis Polancec, Andreja Ambriovic-Ristov, Marijana Radic Stojkovic, Ivo Piantanida, Domagoj Eljuga, Janez Kosmrlj and Maja Osmak
flow cytometric analysis is presented in Figure 2 , and Table 3 . They show that compound 2b arrested the cells in the G1 phase of the cell cycle in dose-dependent manner, even after 24 hours of treatment. At later time points a dose- and time-dependent increase was detected in a fraction of cells with reduced DNA content (subG1), which represents the apoptotic cells subG1 fraction. These results suggest that 2b induces apoptosis in treated cells. Table 3 Effect of compound 2b on the cell cycle of H460 cells Conc. (μM) 24 h 48 h 72 h G1 S
Shu-Hua Zhao, Fan Zhao, Jing-Ying Zheng, Li-Fang Gao, Xue-Jian Zhao and Man-Hua Cui
Knockdown of stat3 expression by RNAi inhibits in vitro growth of human ovarian cancer
Background. The aim of the study was to investigate the suppressive effects of pSilencer2.1-U6-siRNA-stat3 recombinant plasmids on the growth of ovarian cancer in vitro.
Material and methods. Three pairs of DNA template (stat3-1, stat3-2, stat3-3) specific for different target sites on stat3 mRNA were synthesized to reconstruct pSilencer2.1-U6-siRNA-stat3s, which were transfected into SKOV3 cells. The expressions of STAT3, BcL-2, cyclin D1 and C-myc in these cells were detected by Western blot and Northern blot. The cell cycle and the growth were determined by flow cytometry (FCM) and MTT assay, respectively. Cell apoptosis was determined by TUNEL staining.
Results. Of the three siRNAs, only siRNA targeting stat3-3 markedly suppressed the protein expression of stat3 in SKOV3 cells; MTT assay and FCM showed that transfection of stat3-3 siRNA could significantly suppress the growth of SKOV3 cells and arrest the cell cycle in vitro. TUNEL staining also showed massive apoptosis in SKOV3 cells transfected with stat3-3 siRNA.
Conclusions. pSilencer2.1-U6-siRNA-stat3-3 can significantly inhibit the STAT3 expression in human ovarian cancer cells resulting in the inhibition of the cancer growth and the increase of apoptosis of cancer cells.
Friedo Zölzer, Tamare Mußfeldt and Christian Streffer
. Little JB. Delayed initiation of DNA synthesis in irradiated human diploid cells. Nature 1968; 218: 1064-5. 5. Cuddihy AR, Bristow RG. The p53 protein family and radiation sensitivity: Yes or no? Cancer Met Rev 2004; 23: 237-57. 6. Zölzer F, Streffer C. Quiescence in S-phase and G1 arrest induced by irradiation and/or hyperthermia in six human tumour cell lines of different p53 status. Int J Radiat Biol 2000; 76: 717-25. 7. Terasima T, Tolmach LJ. Variations in several responses of HeLa cells to xirradiation during the
Igor Piotrowski, Katarzyna Kulcenty, Wiktoria Maria Suchorska, Agnieszka Skrobała, Małgorzata Skórska, Marta Kruszyna-Mochalska, Anna Kowalik, Weronika Jackowiak and Julian Malicki
radiation. Results indicate that ATM plays an important role in early DSB recognition and can be responsible for inefficient DSB repair, which is in line with conclusions reached by Osipov et al . 24 Authors also observed that doses higher than 0.5 Gy of carbon ion radiation caused an early G2/M arrest dependent on ATM. Some authors suggest that occurrence of this arrest might support DNA DSB repair, while a failure to induce early G2 arrest can be one of the factors responsible for low dose hyper-radiosensitivity (HRS). 28 Low-dose hyper radiosensitivity (HRS
Tomislav Vladusic, Reno Hrascan, Nives Pecina-Slaus, Ivana Vrhovac, Marija Gamulin, Jasna Franekic and Bozo Kruslin
-80. Parry D, Mahony D, Willis K, Lees E. Cyclin D-CDK subunit arrangement is dependent on the availability of competing INK4 and p21 class inhibitors. Mol Cell Biol 1999; 19 : 1775-83. Sherr CJ. Cancer cell cycles. Science 1996; 274 : 1672-77. Zhang HS, Postigo AA, Dean DC., Active transcriptional repression by the Rb-E2F complex mediates G1 arrest triggered by p16INK4a, TGFβ, and contact inhibition. Cell 1999; 97 : 53-61. Bartkova J, Lukas C, Sørensen CS, Rajpert-De Meyts E, Skakkebæk