|ognizant Communication Corporation|
Featuring PRECLINICAL AND CLINICAL CANCER THERAPEUTICS
VOLUME 18, NUMBER 8
Oncology Research, Vol. 18, pp. 359-364
0965-0407/09 $90.00 + .00
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Lentivirus-Mediated Knockdown of Cyclin Y (CCNY) Inhibits Glioma Cell Proliferation
YongGang Xu,1 Zhi Wang,1 Jie Wang,2 JianHua Li,1 HongWei Wang,1 and Wu Yue1
1Department of Minimally Invasive Neurosurgery,
The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
2Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China
Cyclin Y (CCNY) is a novel cyclin and almost nothing is known about its expression level and role in human cancers. In the present study, we found that lentivirus-mediated RNA interference (RNAi) of CCNY significantly downregulated its expression level. More importantly, knockdown of CCNY inhibited cell proliferation, colony formation, and cell cycle progression in glioma cells. These data suggest that CCNY might play an important role in glioma tumorigenisis.
Key words: Cyclin Y (CCNY); Glioma; RNAi
Address correspondence to Wu Yue, Department of Minimally Invasive Neurosurgery, The Fourth Affiliated Hospital of Harbin Medical University, 37 Yiyuan Road, Harbin, 150001, China. Tel: 86-451-87524517; E-mail: firstname.lastname@example.org
Cell Survival or Apoptosis: Rooperol's Role as Anticancer Agent
Gerhardt J. Boukes,1 Brodie B. Daniels,1 Carl F. Albrecht,2 and Maryna van de Venter1
1Department of Biochemistry and Microbiology,
Nelson Mandela Metropolitan University, Port Elizabeth, South Africa
2Cancer Association of South Africa, Bedfordview, South Africa
Nontoxic hypoxoside, isolated from Hypoxis, is converted to cytotoxic rooperol in the presence of b-glucosidase. In this study, we investigated rooperol's mechanism of action. IC50 values of hypoxoside and rooperol were determined against the HeLa, HT-29, and MCF-7 cancer cell lines, and peripheral blood mononuclear cells. DNA cell cycle arrest occurred in late G1 and/or early S phases, associated with increased p21Waf1/Cip1 levels. Apoptosis was shown by caspase-3 and/or caspase-7 activation, phosphatidylserine translocation, DNA fragmentation, cell blebbing, and apoptotic body formation. Increased phospho-Akt, phospho-Bcl-2, and p21Waf1/Cip1 proteins, and cell size correspond to cell survival strategies (associated with endoreduplication).
Key words: Rooperol; Cancer; Apoptosis; Endoreduplication
Address correspondence to Maryna van de Venter, Department of Biochemistry and Microbiology, Nelson Mandela Metropolitan University, PO Box 77000, Port Elizabeth 6031, South Africa. Tel: +27 41 504 2813; Fax: +27 41 504 2814; E-mail: email@example.com
Survivin shRNA Induces Caspase-3-Dependent Apoptosis and Enhances Cisplatin Sensitivity in Squamous Cell Carcinoma of the Tongue
Jian-Hui Xu,1,3,5* An-xun Wang,1,2* Hong-Zhang Huang,1,3 Jian-Guang Wang,4 Chao-Bin Pan,4 and Bin Zhang4
1Department of Oral & Maxillofacial
Surgery, Guanghua School of Stomatology & Hospital of Stomatology,
Sun Yat-sen University, Guangzhou, Guangdong, China
2Department of Oral & Maxillofacial Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
3Institution of Stomatology Research of Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China
4Department of Oral & Maxillofacial Surgery, the Second Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
5Department of Oral and Maxillofacial Surgery, the Affiliated Hospital of Jiangsu University, Zhenjiang, China
Survivin is a member of the inhibitor of apoptosis protein (IAP) family; it is overexpressed in most cancer tissues and induces resistance to chemotherapy. In this study, we investigated whether a short hairpin RNA (shRNA) targeting survivin can induce apoptosis and enhance chemosensitivity to cisplatin in squamous cell carcinoma of the tongue. Results showed that chemosensitivity to cisplatin was surviving dependent in three cell lines (Tca8113, Bca885, and MCF7); higher survivin mRNA expression levels were associated with lower sensitivity to cisplatin. A plasmid-containing survivin shRNA was constructed and transfected into cell line Tca8113. Survivin shRNA inhibited expression of survivin mRNA and protein (63% and 65% inhibition, respectively), significantly inhibited cell proliferation, and enhanced chemosensitivity to cisplatin (p < 0.05). Apoptosis and caspase-3 activity were induced when cells were treated with survivin shRNA and/or cisplatin. Survivin shRNA induced caspase-3-dependent apoptosis and enhanced chemosensitivity to cisplatin in these tongue squamous cell carcinoma cell lines.
Key words: Survivin; shRNA; Apoptosis; Tongue cancer; Cisplatin; Caspase-3; Chemotherapy
Address correspondence to Hong-Zhang Huang, Department of Oral & Maxillofacial Surgery, Guanghua School of Stomatology & Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China 510055. Tel: +86-20-83820121; Fax: +86-20-83822807; E-mail: firstname.lastname@example.org
*These two authors contributed equally to this work.
The Effect of the PPAR-g Agonist Rosiglitazone on Neuroblastoma SK-N-SH Cells in a Metastatic Xenograft Mouse Model
Nina Krieger-Hinck,1 Udo Schumacher,1 Alexander Müller,2 and Ursula Valentiner1
1Department of Anatomy II: Experimental
Morphology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
22Department of Legal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Rosiglitazone, a peroxisome proliferator activated receptor-g (PPAR-g) agonist used in clinical practice to treat type 2 diabetes, has been shown to inhibit neuroblastoma cell proliferation in vitro. In the present study, SK-N-SH neuroblastoma cells were subcutaneously injected into SCID mice and their growth and metastatic behavior under the treatment with rosiglitazone was analyzed. Therapeutic effects were evaluated comparing primary tumor weight, cell proliferation, apoptosis, and number of pulmonary metastasis. Rosiglitazone significantly decreased cell proliferation of the SK-N-SH neuroblastomas from 57.0% in the solvent control to 45.0% and 47.0% in the two treatment groups, respectively. However, primary tumor weight, apoptosis, and metastasis were not considerably influenced. These results indicate that the PPAR-g agonist rosiglitazone has only slight antitumor effects on SK-N-SH neuroblastoma growth in vivo in contrast to in vitro.
Key words: Neuroblastoma; PPAR-g agonists; Rosiglitazone; SCID mouse
Address correspondence to Dr. Ursula Valentiner, Department of Anatomy II: Experimental Morphology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, D-20246 Hamburg, German. Tel: +49 40 7410-53587; Fax: +49 40 7410-55427;E-mail: email@example.com
Frequency of Polymorphisms pro198leu in GPX-1 Gene and ile58thr in MnSOD Gene in the Altitude Ecuadorian Population With Bladder Cancer
César Paz-y-Miño,1 María José Muñoz,1,2 Andrés López-Cortés,1 Alejandro Cabrera,1 Adriana Palacios,1 Bernardo Castro,1 Nelson Paz-y-Miño,3 and María Eugenia Sánchez1
1Instituto de Investigaciones Biomédicas,
Facultad de Ciencias de la Salud, Universidad de las Américas, Quito,
2Laboratorio de Genética Molecular y Citogenética Humana, Escuela de Ciencias Biológicas, Pontificia Universidad Católica del Ecuador, Quito, Ecuador
3Departamento de Urología, Hospital Carlos Andrade Marín, Quito, Ecuador
Bladder cancer represents 8% of all malignancies diagnosed in men and 3% in women. The risk factors for developing bladder cancer, including the incidence rate, morbidity, and mortality, vary according to the ethnic group, exposition rate at work, age, gender, and tobacco consumption. Moreover, there is a risk of developing this carcinoma due to dietary conditions, demonstrating that certain enzymes neutralize oxidative compound derivative of carcinogens, which if not degraded, accumulate in the body and destroy epithelial cells of the bladder, causing an increase in the risk of developing this disease. The detoxifying enzymes inactivate dangerous chemical compounds and anions for the cell; that is, why it is important to know if the polymorphisms pro198leu in GPX-1 and ile58thr in MnSOD are associated with bladder cancer. In this study, 120 individuals were analyzed as controls and 97 individuals with previously diagnosed bladder cancer. In the case of polymorphism pro198leu, highly significant differences were observed and individuals with this polymorphism presented a probability of developing bladder cancer 3.8 times greater than controls (OR = 3.8; 95% CI 2.16-6.78; p < 0.001). No significant differences in polymorphism ile58thr of MnSOD gene occurred when we compared the study population (OR = 2.1; 95% CI 1.26-3.49; p > 0.05). The results indicate that polymorphism of GPX-1 gene influences the risk of developing bladder cancer in the Ecuadorian population, suggesting that more research on detoxifying genes in bladder cancer should be conducted.
Key words: GPX-1; MnSOD; pro198leu; ile58thr; Bladder cancer
Address correspondence to César Paz-y-Miño,
M.D., D.B., Instituto de Investigaciones Biomédicas, Facultad de
Ciencias de la Salud, Universidad de las Américas, Av. de los Granados
y Colimes, 1er P., Quito, Ecuador 1712842. Tel/Fax: (593-2)3340229; E-mail: