Lorenzo Agoni1, Indranil Basu2, Seema Gupta3, Alan Alfieri2, Angela Gambino4, Gary L Goldberg5, E Premkumar Reddy6, Chandan Guha7. 1. Department of Pathology, Albert Einstein College of Medicine, Bronx, New York. 2. Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York. 3. Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York; Biophysics Research Institute of America, North Miami Beach, Florida. 4. Department of Gynecologic Oncology, University of Brescia, Brescia, Italy. 5. Department of Gynecologic Oncology, Albert Einstein College of Medicine, Bronx, New York. 6. Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York. 7. Department of Pathology, Albert Einstein College of Medicine, Bronx, New York; Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York. Electronic address: cguha@montefiore.org.
Abstract
PURPOSE: To compare rigosertib versus cisplatin as an effective radiosensitizing agent for cervical malignancies. METHODS AND MATERIALS: Rigosertib and cisplatin were tested in cervical cancer cell lines, HeLa and C33A. A 24-hour incubation with rigosertib and cisplatin, before irradiation (2-8 Gy), was used for clonogenic survival assays. Cell cycle analysis (propidium iodide staining) and DNA damage (γ-H2AX expression) were evaluated by fluorescence-activated cell sorter cytometry. Rigosertib was also tested in vivo in tumor growth experiments on cervical cancer xenografts. RESULTS: Rigosertib was demonstrated to induce a G2/M block in cancer cells. Survival curve comparison revealed a dose modification factor, as index of radiosensitization effect, of 1.1-1.3 for cisplatin and 1.4-2.2 for rigosertib. With 6-Gy irradiation, an increase in DNA damage of 15%-25% was achieved in both HeLa and C33A cells with cisplatin pretreatment, and a 71-108% increase with rigosertib pretreatment. In vivo tumor growth studies demonstrated higher performance of rigosertib when compared with cisplatin, with 53% longer tumor growth delay. CONCLUSIONS: Rigosertib was more effective than cisplatin when combined with radiation and caused minimal toxicity. These data support the need for clinical trials with rigosertib in combination therapy for patients with cervical carcinoma.
PURPOSE: To compare rigosertib versus cisplatin as an effective radiosensitizing agent for cervical malignancies. METHODS AND MATERIALS: Rigosertib and cisplatin were tested in cervical cancer cell lines, HeLa and C33A. A 24-hour incubation with rigosertib and cisplatin, before irradiation (2-8 Gy), was used for clonogenic survival assays. Cell cycle analysis (propidium iodide staining) and DNA damage (γ-H2AX expression) were evaluated by fluorescence-activated cell sorter cytometry. Rigosertib was also tested in vivo in tumor growth experiments on cervical cancer xenografts. RESULTS:Rigosertib was demonstrated to induce a G2/M block in cancer cells. Survival curve comparison revealed a dose modification factor, as index of radiosensitization effect, of 1.1-1.3 for cisplatin and 1.4-2.2 for rigosertib. With 6-Gy irradiation, an increase in DNA damage of 15%-25% was achieved in both HeLa and C33A cells with cisplatin pretreatment, and a 71-108% increase with rigosertib pretreatment. In vivo tumor growth studies demonstrated higher performance of rigosertib when compared with cisplatin, with 53% longer tumor growth delay. CONCLUSIONS:Rigosertib was more effective than cisplatin when combined with radiation and caused minimal toxicity. These data support the need for clinical trials with rigosertib in combination therapy for patients with cervical carcinoma.
Authors: Kiranmai Gumireddy; M V Ramana Reddy; Stephen C Cosenza; R Boominathan; R Boomi Nathan; Stacey J Baker; Nabisa Papathi; Jiandong Jiang; James Holland; E Premkumar Reddy Journal: Cancer Cell Date: 2005-03 Impact factor: 31.743
Authors: A Prasad; I-W Park; H Allen; X Zhang; M V R Reddy; R Boominathan; E P Reddy; J E Groopman Journal: Oncogene Date: 2009-02-09 Impact factor: 9.867
Authors: Sai Krishna Athuluri-Divakar; Rodrigo Vasquez-Del Carpio; Kaushik Dutta; Stacey J Baker; Stephen C Cosenza; Indranil Basu; Yogesh K Gupta; M V Ramana Reddy; Lynn Ueno; Jonathan R Hart; Peter K Vogt; David Mulholland; Chandan Guha; Aneel K Aggarwal; E Premkumar Reddy Journal: Cell Date: 2016-04-21 Impact factor: 41.582
Authors: Mostafa A Askar; Heba As El-Nashar; Mahmood A Al-Azzawi; Sahar S Abdel Rahman; Omama E Elshawi Journal: Breast Cancer (Auckl) Date: 2022-03-25
Authors: Peter Dietrich; Kim Freese; Abdo Mahli; Wolfgang Erwin Thasler; Claus Hellerbrand; Anja Katrin Bosserhoff Journal: Oncotarget Date: 2017-12-11
Authors: Ji-Ae Shin; Lee-Han Kim; Sook-Jeong Lee; Joseph H Jeong; Ji-Youn Jung; Hae Nim Lee; In-Sun Hong; Sung-Dae Cho Journal: Oncotarget Date: 2015-11-03