Young Seok Kim1, Mun Jung Kang, Yong Mee Cho. 1. Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 388-1 Pungnap-2dong, Songpa-gu, Seoul, 138-736, Republic of Korea. yongcho@amc.seoul.kr.
Abstract
BACKGROUND: Cancer stem cells (CSCs) are resistant to radiotherapy and are responsible for tumor recurrence of various malignant tumors, including prostate cancer. MATERIALS AND METHODS: In order to define the radioresistance mechanism of prostate CSCs, their proliferative activity, cell cycle distribution, expression of CD133 stem cell marker, reactive oxygen species (ROS) production, and DNA repair efficiency were examined using prostatospheres and adherent LNCaP cells as a model of prostate CSC and bulk model of differentiated cells, respectively. RESULTS: Compared to adherent cells, prostatospheres exhibited greater number of low-to-intermediate ROS-producing cells and CD133-positive cells. Prostatospheres showed higher expression of DNA repair proteins after ionizing radiation (IR). CONCLUSION: Low vulnerability to ROS-induced cellular damage and the efficient repair of IR-induced DNA injury may explain the radioresistance of prostate CSCs. Therefore, increasing ROS-induced cytotoxicity and inhibition of DNA repair in prostate CSCs may help achieve complete eradication of prostate CSCs by radiotherapy.
BACKGROUND: Cancer stem cells (CSCs) are resistant to radiotherapy and are responsible for tumor recurrence of various malignant tumors, including prostate cancer. MATERIALS AND METHODS: In order to define the radioresistance mechanism of prostate CSCs, their proliferative activity, cell cycle distribution, expression of CD133 stem cell marker, reactive oxygen species (ROS) production, and DNA repair efficiency were examined using prostatospheres and adherent LNCaP cells as a model of prostate CSC and bulk model of differentiated cells, respectively. RESULTS: Compared to adherent cells, prostatospheres exhibited greater number of low-to-intermediate ROS-producing cells and CD133-positive cells. Prostatospheres showed higher expression of DNA repair proteins after ionizing radiation (IR). CONCLUSION: Low vulnerability to ROS-induced cellular damage and the efficient repair of IR-induced DNA injury may explain the radioresistance of prostate CSCs. Therefore, increasing ROS-induced cytotoxicity and inhibition of DNA repair in prostate CSCs may help achieve complete eradication of prostate CSCs by radiotherapy.
Entities:
Keywords:
DNA repair; Prostatic neoplasms; neoplastic stem cells; radioresistance; radiotherapy; reactive oxygen species
Authors: Sabine A S Langie; Gudrun Koppen; Daniel Desaulniers; Fahd Al-Mulla; Rabeah Al-Temaimi; Amedeo Amedei; Amaya Azqueta; William H Bisson; Dustin G Brown; Gunnar Brunborg; Amelia K Charles; Tao Chen; Annamaria Colacci; Firouz Darroudi; Stefano Forte; Laetitia Gonzalez; Roslida A Hamid; Lisbeth E Knudsen; Luc Leyns; Adela Lopez de Cerain Salsamendi; Lorenzo Memeo; Chiara Mondello; Carmel Mothersill; Ann-Karin Olsen; Sofia Pavanello; Jayadev Raju; Emilio Rojas; Rabindra Roy; Elizabeth P Ryan; Patricia Ostrosky-Wegman; Hosni K Salem; A Ivana Scovassi; Neetu Singh; Monica Vaccari; Frederik J Van Schooten; Mahara Valverde; Jordan Woodrick; Luoping Zhang; Nik van Larebeke; Micheline Kirsch-Volders; Andrew R Collins Journal: Carcinogenesis Date: 2015-06 Impact factor: 4.944