Oncology Research 19(7) Abstracts

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Oncology Research, Vol. 19, pp. 303–309, 2011
0965-0407/11 $90.00 + .00
DOI: 10.3727/096504011X13079697132790
E-ISSN 1555-3906
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Combretastatin A4 Phosphate Induces Programmed Cell Death in Vascular Endothelial Cells

Xueqiang Ding,* Zhaoqiang Zhang,* Su Li,† and Anxun Wang*

*Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China
†Department of Medicine, Tumor Hospital, Sun Yat-sen University, Guangzhou, P.R. China

Combretastatin A4 phosphate (CA4P) is currently undergoing clinical trials as a tumor vascular-targeting agent. Here, we defined the antivascular effect and programmed cell death (PCD) induced by CA4P in vascular endothelial cells. CA4P induced time- and dose-dependent antiproliferative activities against human umbilical vein endothelial cells (HUVECs), and caused G2/M arrest accompanied with DNA fragmentation. The in vitro wound assay and tube formation assay indicated that CA4P potently inhibited migration of endothelial cells and tube formation. The apoptosis and autophagy marker microtubule-associated protein light chain 3 (LC3)-II was induced in CA4P-treated HUVECs. The current study demonstrates that CA4P is a promising antivascular agent with potent PCD-inducing activities. CA4P may be useful in the treatment of cancer and hemangioma.

Key words: Combretastatin A4 phosphate (CA4P); Angiogenesis; Autophagy; Apoptosis; Programmed cell death

Address correspondence to Anxun Wang, Department of Oral and Maxillofacial Surgery, First Affiliated Hospital, Sun-Yat-Sen University, 58 Zhongshan Road II, Guangzhou, 510080 P.R. China. Tel: +86-0-13724896216; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 19, pp. 311–321, 2011
0965-0407/11 $90.00 + .00
DOI: 10.3727/096504011X13079697132844
E-ISSN 1555-3906
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

5-Fluorouracil Increases the Chemopreventive Potentials of Resveratrol Through DNA Damage and MAPK Signaling Pathway in Human Colorectal Cancer Cells

Purusottam Mohapatra,* Ranjan Preet,* Maitrayee Choudhuri,* Tathagata Choudhuri,† and Chanakya Nath Kundu*

*KIIT School of Biotechnology, KIIT University, Orissa, India
†Institute of Life Sciences, Orissa, India

Resveratrol (Res) can modulate multiple cellular pathways relevant for tumorigenesis but is less effective in colon cancer compared to breast cancer. To increase the chemopreventive potential of Res in combination with 5-fluorouracil (5-FU), a systematic study was carried out in colon cancer cells. HCT-116 cells were treated with Res and 5-FU and several cell-based assays, such as MTT, clonogenic, wound healing, DAPI, comet assay, and Western blot, were performed. A significant inhibition of cell proliferation, migration, and increased apoptosis were observed when moderate concentration of Res (15 μM) was associated with very low concentration of 5-FU (0.5 μM). This combination caused apoptosis by blocking the cells at S phase and enhanced the DNA damage. Expression levels of p-JNK and p-p38 were increased without affecting p-ERK. 5-FU could be used as a therapeutic modality to improve efficacy of Res-based chemotherapy against colon cancer.

Key words: Colorectal cancer; Resveratrol; 5-Fluorouracil; Combination therapy; DNA damage; MAPK

Address correspondence to Chanakya Nath Kundu, School of Biotechnology, KIIT University, Campus-11, Patia, Bhubaneswar, Orissa, 751024, India. Tel: +91-0674-2725466; Fax: +91-0674-2725466; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 19, pp. 323–333, 2011
0965-0407/11 $90.00 + .00
DOI: 10.3727/096504011X13079697132880
E-ISSN 1555-3906
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Antiproliferative Effect of Newcastle Disease Virus Strain D90 on Human Lung Cancer Cell Line A549

Fang Fu,* Ming Zhao,† Yu-Ju Yang,‡ Guang-Zhi Tong,§ Bao-Feng Yang,† Chun Song,† and Xi Li*

*Division of Swine Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, P.R. China
†Harbin Medical University, Harbin, P.R. China
‡Department of Science, Harbin University, Harbin, P.R. China
§Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, P.R. China

Newcastle disease virus (NDV) and variants of this virus have oncolytic properties and are potential anticancer agents. The objective of this study was to compare the effect of NDV strain D90 and strain D93 isolated from natural sources on human non-small cell lung cancer (NSCLC) cell line A549. We determined the 50% embryo infective dose (EID50) and 50% tissue culture infective dose (TCID50) of the NDV strains. The MTT assay was used to evaluate the effects of NDV strains on cell viability. We determined the expression of Annexin V and Bcl-2 proteins in NDV-infected cells. Light microscopy and electron microscopy indicated that the D90 strain significantly altered cell morphology and reduced cell viability, while strain D93 had negligible effects. Neither strain had a significant effect on normal cultured fetal liver cells. We used acridine orange staining to show that strain D90 (but not strain D93) induced nuclear fragmentation of A549 cells. An Annexin V-based apoptosis assay indicated that strain D90 (but not strain D93) caused significant apoptosis of A549 cells. Moreover, strain D90 (but not strain D93) significantly repressed the expression of Bcl-2 (an antiapoptotic protein) in A549 cells. Taken together, our results indicate that NDV strain D90 (but not strain D93) had no significant effect on normal cultured cells, but induced apoptosis of cultured NSCLC cells via a caspase-dependent pathway. These results suggest that NDV strain D90 has potential as an anticancer agent.

Key words: Newcastle disease virus (NDV); Cell line A549; Apoptosis; Hemaglutinin; Non-small cell lung cancer

Address correspondence to Xi Li, Ph.D., Division of Swine Infectious Diseases, National Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, P.R. China. Tel: +86-0451-18946066129; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 19, pp. 335–348, 2011
0965-0407/11 $90.00 + .00
DOI: 10.3727/096504011X13079697132925
E-ISSN 1555-3906
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Fibronectin–Integrin (α5β1) Modulates Migration and Invasion of Murine Melanoma Cell Line B16F10 by Involving MMP-9

Hrishikesh Sil, Triparna Sen, and Amitava Chatterjee

Department of Receptor Biology & Tumour Metastasis, Chittaranjan National Cancer Institute, Kolkata, India

Cell adhesion to extracellular matrix (ECM) initiates signaling cascade regulated by cell surface integrin receptors, which affects the proliferation and invasion of cells. Cells cultured in the presence of ECM ligand fibronectin (FN) stimulate secretion of matrix metalloproteinases (MMPs), facilitating cancer cell invasion and metastasis. Among all the members of the MMP family, MMP-9 is of crucial importance in tumor invasion and metastasis. The present study aims at studying the effects of integrin receptor α5β1 and its ligand FN on expression of MMP-9 in murine melanoma cell line B16F10 and understanding the molecular mechanism(s) involved. The main experimental methods performed in the study were gelatin zymography, immunoblot, real-time RT-PCR, immunocytochemistry, enzyme linked immunosorbent assay (ELISA), transwell chamber assay, and in vivo metastasis assay in syngenic (C57BL6J) mice. The study reports that FN induces the activity, mRNA, and protein expression of MMP-9 and initiates its proteolytic activation in B16F10 cells. Blockage of the α5 receptor abrogated the FN-mediated stimulatory response on MMP-9 in B16F10 cells. Inhibitor studies and immunoblot analysis strongly suggest the involvement of focal adhesion kinase (FAK), extracellular regulated kinase (ERK), and phosphatidylinositol-3-kinase (PI-3K) in the FNmediated responses. Immunocytochemical analysis showed the nuclear localization of nuclear factor-κB (NF-κB) might lead to activation of MMP-9 gene upon FN treatment. This study demonstrates that integrin receptor α5β1 and FN interaction induces the invasive potential of B16F10 cells and MMP-9 induction is the downstream effectors in the process. This system serves as a novel model system to understand the molecular mechanism of melanoma growth and invasion.

Key words: Integrin; Fibronectin; MMP-9; Murine melanoma; Signaling

Address correspondence to Amitava Chatterjee, Ph.D., Head, Department of Receptor Biology & Tumour Metastasis, Chittaranjan National Cancer Institute, 37, S P Mukherjee Road, Kolkata-700 026, West Bengal, India. Tel: 91-33-9830128320; Fax: 91-033-2475-7606; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 19, pp. 349–363, 2011
0965-0407/11 $90.00 + .00
DOI: 10.3727/096504011X13079697132961
E-ISSN 1555-3906
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Single-Agent Inhibition of Chk1 Is Antiproliferative in Human Cancer Cell Lines In Vitro and Inhibits Tumor Xenograft Growth In Vivo

Kurtis D. Davies,* Michael J. Humphries,† Francis X. Sullivan,‡ Ira von Carlowitz,* Yvan Le Huerou,§ Peter J. Mohr,§ Bin Wang,§ James F. Blake,¶ Michael A. Lyon,§ Indrani Gunawardana,§ Mark Chicarelli,§ Eli Wallace,§ and Stefan Gross*

*Cell Biology, Array BioPharma, Inc., Boulder, CO, USA
†Pharmacology, Array BioPharma, Inc., Boulder, CO, USA
‡Enzymology, Array BioPharma, Inc., Boulder, CO, USA
§Chemistry, Array BioPharma, Inc., Boulder, CO, USA
¶Computational Research, Array BioPharma, Inc., Boulder, CO, USA

Chk1 is a serine/threonine kinase that plays several important roles in the cellular response to genotoxic stress. Since many current standard-of-care therapies for human cancer directly damage DNA or inhibit DNA synthesis, there is interest in using small molecule inhibitors of Chk1 to potentiate their clinical activity. Additionally, Chk1 is known to be critically involved in cell cycle progression of unperturbed cells. Therefore, it is plausible that treatment with a Chk1 inhibitor alone could also be an efficacious cancer therapy. Here we report that Chk1-A, a potent and highly selective small molecule inhibitor of Chk1, is antiproliferative as a single agent in a variety of human cancer cell lines in vitro. The inhibition of proliferation is associated with collapse of DNA replication and apoptosis. Rapid decreases in inhibitory phosphorylation of CDKs and a concomitant increase in CDK kinase activity and chromatin loading of Cdc45 suggest that the antiproliferative and proapoptotic activity of Chk1-A is at least in part due to deregulation of DNA synthesis. We extend these in vitro studies by demonstrating that Chk1-A inhibits the growth of tumor xenografts in vivo in a treatment regimen that is well tolerated. Together, these results suggest that single-agent inhibition of Chk1 may be an effective treatment strategy for selected human malignancies.

Key words: Checkpoint kinase 1 (Chk1); Checkpoint; Chemopotentiation; Cyclin-dependent kinase; Cell cycle

Address correspondence to Kurtis D. Davies, Array BioPharma, Inc., 3200 Walnut St., Boulder, CO 80301, USA. Tel: 303-669-9861; Fax: 303-867-5701; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 19, pp. 365–373, 2011
0965-0407/11 $90.00 + .00
DOI: 10.3727/096504011X13079697133005
E-ISSN 1555-3906
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

An Imbalance in Oxidant/Antioxidant Dynamics: Correlation With Therapeutic Response in Patients With Carcinoma of Posterior One Third of the Tongue

Manoj Sharma,* Medha Rajappa,† Abhigyan Satyam,‡ and Alpana Sharma‡

*Department of Radiotherapy, Maulana Azad Medical College and associated Lok Nayak Hospital, New Delhi, India
†Department of Biochemistry, Maulana Azad Medical College and associated Lok Nayak Hospital, New Delhi, India
‡Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India

The objective was to study the alterations in circulating pro-/antioxidants in patients with cancer of the posterior one third of the tongue, before and after concomitant chemoradiation, and to assess variation in their levels to therapeutic response. Sixty patients with newly diagnosed squamous cell carcinoma of the posterior one third of the tongue and 60 healthy controls were enrolled. Blood samples were collected before and after chemoradiation and after 3 months of follow-up. Pro-/antioxidant levels were estimated using standard methods. Response to therapy was assessed during and after therapy and after 3 months of follow-up. Pretreatment levels of lipid peroxide were significantly elevated while antioxidant levels were lowered in cancer patients compared to controls. After chemotherapy, lipid peroxidation showed a significant decline, while antioxidants showed a significant rise in complete responders, compared with partial/nonresponders, and remained highly significant after therapy and during follow-up. Pretreatment levels of antioxidant–oxidant parameters and the extent of their change during treatment can predict the therapeutic response to concomitant chemoradiation in carcinoma tongue.

Key words: Antioxidant enzymes; Cancer of posterior one third of the tongue; Conjugated dienes; Glutathione; Lipid peroxidation; Concomitant chemoradiation; Therapeutic response; Vitamin C; Vitamin E

Address correspondence to Dr. Alpana Sharma, Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Dellhi-110029, India. Tel: 0091-98990-61974; Fax: 0091-11-26588641 or 0091-11-26588663; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it