Oncology Research 19(5) Abstracts

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Oncology Research, Vol. 19, pp. 179–191, 2011
0965-0407/11 $90.00 + .00
DOI: 10.3727/096504011X12970940207724
E-ISSN 1555-3906
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Azadirachta indica Exerts Chemopreventive Action Against Murine Skin Cancer: Studies on Histopathological, Ultrastructural Changes and Modulation of NF-κB, AP-1, and STAT1

N. Arora, M. P. Bansal, and A. Koul

Department of Biophysics, Basic Medical Sciences Block, Panjab University, Chandigarh, India

The present study reports the histopathological, ultrastructural changes and modulation of NF-κB, AP-1, and STAT 1 during skin carcinogenesis in LACA mice and its intervention with Azadirachta indica. Skin tumors were induced by topical application of 7,12-dimethylbenz(a)anthracene (DMBA) (500 nmol/100 μl for 2 weeks) followed by 12-O-tetradecanoylphorbol-13-acetate (TPA) (1.7 nmol/100 μl of acetone, twice weekly) as a promoter. Male LACA mice were divided into four groups: Control, DMBA/TPA, aqueous Azadirachta indica leaf extract (AAILE), and AAILE + DMBA/TPA. AAILE was administered orally at a dose level of 300 mg/kg body weight three times a week for 20 weeks. Topical application of DMBA/TPA to the skin resulted in well-developed squamous cell carcinomas characterized by hyperproliferation, hyperkeratosis, and corrugation of the epidermis. Degenerative changes were observed in the tumors of AAILE + DMBA/TPA-treated animals. Scanning electron microscopy revealed surface disruptions and certain rounded structures on the skin tumors of DMBA/TPA-treated animals. Topographical changes were also observed in the tumors of AAILE + DMBA/TPA-treated animals, which resembled regions of degeneration. Tumors obtained in DMBA/TPA group were associated with enhanced expression of NF-κB and AP-1 when compared to the control counterparts. Inhibition in tumorigenesis in response to A. indica treatment was accompanied by an overexpression of STAT 1 and AP-1 and decrease in NF-êB expression. The results of the present study provide a basis for the chemopreventive potential of A. indica against murine skin carcinogenesis.

Key words: Phytochemicals; Transcription factors; Skin tumors; Azadirachta indica

Address correspondence to Dr. Ashwani Koul, Department of Biophysics, Basic Medical Sciences Block, Panjab University, Chandigarh-160014, India. Tel: +91-172-2534124; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it or This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 19, pp. 193–201, 2011
0965-0407/11 $90.00 + .00
DOI: 10.3727/096504011X12970940207760
E-ISSN 1555-3906
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Knockdown of MED19 by Lentivirus-Mediated shRNA in Human Osteosarcoma Cells Inhibits Cell Proliferation by Inducing Cell Cycle Arrest in the G0/G1 Phase

Tiejun Wang,* Ling Hao,† Yan Feng,* Gang Wang,* Daming Qin,* and Guishan Gu*

*Department of Orthopaedics, The First Hospital of Jilin University, Changchun, China
†Department of Otorhinolaryngology, Zhongshan Hospital Xiamen University, Xiamen, China

MED19 is a subunit of the mediator complex, which is a coactivator of RNA polymerase II and also interacts with the downstream coding region of many genes. However, the role of MED19 in osteosarcoma is unknown. In the present study, we applied lentivirus-mediated short hairpin RNA (shRNA)-triggered RNA interference to downregulate MED19 expression in human osteosarcoma SaOS-2 and U2OS cells. Knockdown of MED19 expression was confirmed by real-time PCR and Western blot. It was found that silencing of MED19 resulted in decreased cell viability, colony formation capacity, and DNA synthesis ability in both cells, as well as the G0/G1 phase cell cycle arrest. These results implied that MED19 played an important role in cell growth and cell cycle progression of human osteosarcoma cells. MED19 may be an attractive candidate for the therapeutic target in osteosarcoma.

Key words: MED19; Proliferation; Osteosarcoma; RNA interference

Address correspondence to Guishan Gu, Department of Orthopaedics, the First Hospital of Jilin University, 71 Xinmin Avenue, Changchun 130021, Jilin Province, China. Tel: 86 431 88782457; Fax: 86 431 88782588; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it or This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 19, pp. 203–216, 2011
0965-0407/11 $90.00 + .00
DOI: 10.3727/096504011X12970940207805
E-ISSN 1555-3906
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved


Anticancer Effects of Fullerene [C60] Included in Polyethylene Glycol Combined With Visible Light Irradiation Through ROS Generation and DNA Fragmentation on Fibrosarcoma Cells With Scarce Cytotoxicity to Normal Fibroblasts

Feng Liao, Yasukazu Saitoh, and Nobuhiko Miwa

Laboratory of Cell-Death Control BioTechnology, Department of Life Sciences, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, Shobara, Hiroshima, Japan

Fullerene [C60] included in polyethylene glycol (PEG) at a composing ratio of 1:350 w/w was examined for anticancer effects upon photodynamic therapy (PDT). Human connective tissue-derived fibrosarcoma cells HT1080 were decreased for a viability of 50% or 30%, by 3-h administration with PEG-fullerene [C60] at 50 or 100 ppm fullerene [C60] equivalent, respectively, subsequent rinsing out and irradiation with visible light (400–600 nm, 140 J/cm2:450-fold as intense as in average outdoor), whereas the same tissue typederived normal fibroblastic cells DUMS16 retained a viability of 93% or 85% under the same conditions. Anticancer effects were dependent on PEG-fullerene [C60] concentrations and irradiation doses, and scarcely exerted by PEG-fullerene [C60] alone, irradiation alone, or by fullerene [C60]-free PEG combined with irradiation, suggesting that the active principle may be fullerene [C60] as small as 0.0028 wt% versus the whole compound. Irradiation with PEG-fullerene [C60] occurred in intracellular DNA fragmentation according to TUNEL assay, and produced reactive oxygen species (ROS) such as hydroperoxides and peroxyl radicals or superoxide anion radicals in HT1080 cells as demonstrated by CDCFH-DA assay or nitroblue tetrazolium assay, respectively. Thus, PEG-fullerene [C60] is expected to be applied to anticancer PDT with scarce side effects on normal cells.

Key words: Fullerene [C60] included in polyethylene glycol; Photodynamic therapy (PDT); Irradiation; Reactive Oxygen Species (ROS); DNA fragmentation

Address correspondence to Prof. Nobuhiko Miwa, Laboratory of Cell-Death Control BioTechnology, Department of Life Sciences, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, Nanatsuka 562, Shobara, Hiroshima 727-0023, Japan. Tel: +81-824-74-1754; Fax: +81-824-74-1754; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 19, pp. 217–223, 2011
0965-0407/11 $90.00 + .00
DOI: 10.3727/096504011X12970940207841
E-ISSN 1555-3906
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Antitumor Effect of Suberoylanilide Hydroxamic Acid and Topotecan in Renal Cancer Cells

Akinori Sato, Takako Asano, Akio Horiguchi, Keiichi Ito, Makoto Sumitomo, and Tomohiko Asano

Department of Urology, National Defense Medical College, Tokorozawa, Saitama, Japan

The treatment modality for advanced renal cancer is limited. The development of novel systemic therapies has long been waited for. Suberoylanilide hydroxamic acid (SAHA) is one of the most potent histone deacetylase (HDAC) inhibitors, which are promising novel anticancer agents. SAHA has already been tested in phase II clinical trials; however, its effectiveness has been found to be limited. Recently, the combination of SAHA and topoisomerase I inhibitor, topotecan, was shown to be effective, but this treatment strategy has not been tested in renal cancer cells. In the present study, we found that the combination of SAHA and topotecan effectively inhibited the growth of renal cancer cells by suppressing the expression of cyclin-dependent kinase (CDK) 4 and cyclin D1, and promoting retinoblastoma protein (Rb) dephosphorylation. Furthermore, the combination therapy was found to inhibit both the function and expression of HDACs, which may be one of the main mechanisms of the combination therapy. To the best of our knowledge, this is the first report that has revealed the combined beneficial effect of SAHA and topotecan on renal cancer cells. Combining SAHA and topotecan is thus a promising approach to the treatment of renal cancer.

Key words: Renal cancer; Histone deacetylase (HDAC); Suberoylanilide hydroxamic acid (SAHA); Topotecan

Address correspondence to Akinori Sato, Department of Urology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan. Tel: +81-4-2995-1676; Fax: +81-4-2996-5210; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 19, pp. 225–235, 2011
0965-0407/11 $90.00 + .00
DOI: 10.3727/096504011X12970940207887
E-ISSN 1555-3906
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Three-Dimensional Conformal Radiation Therapy of Spontaneous Benign Prostatic Hyperplasia in Canines

Pinting Zhao,*1 Shaoping Lu,†1 Yilin Yang,‡ Qiuju Shao,* and Jun Liang*

*Department of Radiotherapy, Tangdu Hospital, The Fourth Military Medical University Xi’an, Shanxi Province, P.R. China
†Department of Cardiology, Tangdu Hospital, The Fourth Military Medical University Xi’an, Shanxi Province, P.R. China
‡Department of Ultrasound Diagnosis, Tangdu Hospital, The Fourth Military Medical University Xi’an, Shanxi Province, P.R. China

The purpose of this study was to determine the effect and possible mechanism of three-dimensional conformal stereotactic radiation therapy (3D-CRT) for the treatment of spontaneous benign prostatic hyperplasia (BPH) in a canine model. Eight canines (7–15 years old) with spontaneous benign prostatic hyperplasia (prostate volume > 18 cm3) were used as experimental models. The prostates were directly exposed to 3DCRT at a total dose of 14 Gy. Serum prostate-specific antigen (PSA) and prostate acid phosphatase (PAP), prostate volume (measured by transrectal ultrasound), apoptosis index [AI, measured by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)], proliferation index [PI, measured by proliferating cell nuclear antigen (PCNA) expression], α-SMA, Bax, and bFGF were measured before and after radiation therapy. Histopathology of the prostate, rectum, and bladder tissue was also examined before and after irradiation. 3D-CRT treatment significantly decreased prostate volume, and the PI, PSA, and α-SMA, but significantly increased the AI, and had no effect on PAP. There was no evidence of Bax expression before or after irradiation. Irradiation led to no detectable symptoms of diarrhea or changes in stool, but did lead to minor bladder injury, based on light microscopy, scanning electron microscopy, and transmission electron microscopy. In our canine model, 3D-CRT is an effective, noninvasive treatment of BPH that is associated with minimal side effects. Our treatment appeared to reduce prostate size by treatment of the underlying pathological processes.

Key words: Three-dimensional conformal stereotactic radiation therapy (3D-CRT); Benign prostatic hyperplasia (BPH); Canine models; Prostate-specific antigen (PSA)

1These authors provided equal contribution in this study.
Address correspondence to Jun Liang, Department of Radiotherapy, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shanxi Province 710038, P.R. China. Tel: 86-29-84777181; Fax: 86-29-84777181; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it or This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 19, pp. 237–243, 2011
0965-0407/11 $90.00 + .00
DOI: 10.3727/096504011X12970940207922
E-ISSN 1555-3906
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Indole-3-carbinol Inhibits Prostate Cancer Cell Migration via Degradation of β-Catenin

Yun-Mi Jeong,* Hailan Li,* Su Yeon Kim,* Hye-Young Yun,* Kwang Jin Baek,* Nyoun Soo Kwon,* Soon Chul Myung,†‡ and Dong-Seok Kim*‡

*Department of Biochemistry, Chung-Ang University College of Medicine, Seoul, Korea
†Department of Urology, Chung-Ang University College of Medicine, Seoul, Korea
‡Research Institute for Translational System Biomics, Chung-Ang University College of Medicine, Seoul, Korea

We determined whether indole-3-carbinol (I3C) could affect DU145 human prostate carcinoma cell migration to prevent the development and progression of prostate cancer. Although previous studies have shown anticancer properties of I3C in various cancer cell lines, it has not been determined how I3C regulates epidermal growth factor (EGF)-induced migration and related signaling pathways. DU145 cells were treated with I3C (100 μM) in the absence or presence of EGF (10 ng/ml). Our results showed that I3C significantly inhibited DU145 cell migration with and without EGF stimulation. It has been reported that the β-catenin signaling pathway controls androgen receptor (AR)-mediated prostate cancer progression, which plays a key role in the metastasis of prostate cancer. Western blot analysis demonstrated that I3C led to the phosphorylation of β-catenin and subsequent degradation of β-catenin in the absence and presence of EGF. In contrast, I3C did not have any effect on the expression of β-catenin mRNA. From these results, we suggest that I3C inhibits EGF (dependent or independent)-induced DU145 cell migration through β-catenin degradation.

Key words: Indole-3-carbinol; Prostate cancer; Migration; β-Catenin

Address correspondence to Dong-Seok Kim, Ph.D., Department of Biochemistry, Chung-Ang University College of Medicine, 221 Heukseokdong Dongjak-gu, Seoul 156-756, Korea. Tel/Fax: +82-2-820-5768; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it