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MR Molecular Imaging of Prostate Cancer with a Small Molecular CLT1 Peptide Targeted Contrast Agent
Published on: September 3, 2013
Modulation of prostate carcinoma cell growth and apoptosis by chromogranin A
Dah-Shyong Yu1, Dar-Shih Hsieh, Sun-Yran Chang
1Uro-Oncology Laboratory, Division of Urology, Department of Surgery, Tri-Service General Hospital, No. 325, Section 2 Cheng-Gung Road, Nei-Hu, Taipei, Taiwan 114, Republic of China.
Purpose:
We elucidated the effect and possible pathways of chromogranin A in regulating prostatic cancer cell growth.
Materials And Methods:
Chromogranin A expression in prostatic cancer cell lines were detected with immunofluorescence flow cytometry (FCM) and the inhibition of cell growth due to chromogranin A antibody was measured using microculture tetrazolium. Cell cycle and RNA changes were evaluated with acridine orange FCM. Intracellular chromogranin A variations were detected with FCM, as were apoptotic changes, p53, Fas and tumor necrosis factor-alpha. Apoptosis and caspase-3 expression of tumor cells was assessed with dual immunohistochemical staining.
Results:
Increased chromogranin A expression was observed in PC-3, DU145 and LNCap cells independent of hormone dependence. Dose and time dependent growth inhibition occurred at 12 hours. Chromogranin A antibody arrested PC3 cells in the S-phase immediately after treatment. The number of G0/G1 and G2/M cells subsequently decreased. PC3 tumor cells had transiently increased RNA at 12 hours with a marked decrease at 48 hours. Decreasing chromogranin A expression started at 12 hours and was most prominent at 48 hours. Apoptotic cells markedly increased at 12 hours with an increase in p53, Fas and tumor necrosis factor-alpha (Fas more than the others). Increased apoptotic cell and caspase-3 expression was observed on immunohistochemical stains.
Conclusions:
Chromogranin A is an important neuropeptide regulating the growth of prostate cancer cells. Specific antibodies can suppress its function through apoptotic pathways (Fas and caspase-3), leading to programmed cell death. Chromogranin A antibody mediated apoptosis may be a specific alternative treatment for prostate cancer.
