Cytotoxic and anti-angiogenic effects of zoledronic acid in DU-145 and PC-3 prostate cancer cell lines
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ORIGINAL ARTICLE
Cytotoxic and anti‑angiogenic effects of zoledronic acid in DU‑145 and PC‑3 prostate cancer cell lines Cenk Gokalp1 Received: 17 July 2020 / Accepted: 10 September 2020 / Published online: 29 September 2020 © Springer Nature B.V. 2020
Abstract This study aims to investigate the apoptotic and anti-angiogenic effect of Zoledronic acid on hormone-refractory prostate cancer cell lines. XTT cell proliferation assay used to assess cytotoxicity. Caspase 3/7 activity and DNA fragmentation were measured to verify apoptosis. Angiogenic cytokine profiles investigated using the human angiogenesis antibody array I. Administration of Zoledronic acid on PC-3 and DU-145 prostate cancer cell lines resulted in increased cytotoxicity and apoptosis with a time- and dose-related manner. Also, the administration of Zoledronic acid significantly reduced several angiogenic cytokine productions in PC-3 and DU-145 cell lines. Zoledronic acid successfully induced apoptosis and reduced various angiogenic cytokine production in hormone-refractory prostate cancer cell lines. Novel treatment protocols may be developed in the future with chemotherapeutic combinations for the treatment of prostate cancer. Keywords Prostate cancer · Zoledronic acid · PC-3 · DU-145 · Angiogenesis
Introduction
Materials and methods
Prostate carcinoma is the most common type and the second most common cause of cancer-related deaths in the male population [1]. The management options may range from patient surveillance to surgery, radiotherapy, and hormone therapy according to the risk categorization of the patient [2, 3]. The most common metastatic sites in patients with prostate cancer are bones, lymph nodes, liver, and thorax [4]. PC-3 and DU-145 are prostate cancer cell lines that derive from either bone or brain metastasis with partially different genes and/or protein profiles [5]. Bisphosphonates are generally preferred for the treatment of bone metastasis because of the inhibitory effects of the drugs on osteoclasts that result in both the palliation of the bone metastasis and the treatment of malignant hypercalcemia. Zoledronic acid (ZoA) is widely used in prostate cancer cases with bone metastasis. Herein, we investigated the cytotoxic and anti-angiogenic effects of ZoA in hormone-refractory PC-3 and DU-145 prostate cancer cell lines.
Cell lines and culture medium
* Cenk Gokalp [email protected] 1
Department of Internal Medicine, Faculty of Medicine, Ege University, Kazim Dirik Mah, 35100 Izmir, Turkey
Human prostate cancer cell lines, PC-3 and DU-145, were provided from the Interlab Cell Line Collection (Geneva, Italy). These cell lines were placed in 50 ml dishes in RPMI 1640 medium for culture propagation; were plated in a single layer with the addition of 2 μM glutamine, 10% fetal bovine serum and 1% penicillin–streptomycin (Corning Life Sciences, UK). Cell culture procedures were performed in Hood (NuAire, USA) and incubator (NuAire, USA). Hood was sterilized with ultraviolet light for 30 min and then rinsed with alcohol. PC-
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