Phorbol ester inhibits DNA damage-induced apoptosis in U937 cells through activation of protein kinase C

• Published in: Life sciences (1973) Vol. 65; no. 21; pp. 2251 - 2258
• Main Authors: Kaneko, Yoko S., Ikeda, Kyoji, Nakanishi, Makoto
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 1999
• Subjects: 25(OH) 2D 3; 4αPDD; apoptosis; Apoptosis - drug effects; Apoptosis - radiation effects; Blotting, Northern; Bucladesine - pharmacology; Calcitriol - pharmacology; Cell Differentiation - drug effects; db-cAMP; DNA Damage - physiology; Enzyme Activation - drug effects; Enzyme Activation - radiation effects; Enzyme Inhibitors - pharmacology; Flow Cytometry; Humans; Naphthalenes - pharmacology; PKC; PMA; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - metabolism; Tetradecanoylphorbol Acetate - pharmacology; U937 Cells; Ultraviolet Rays; 1; db-cAMP; PMA; 25(OH) 2D 3; U937 cells; 4αPDD; PKC; apoptosis
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/S0024-3205(99)00490-7

The effects of phorbol 12-myristate 13-acetate (PMA) on DNA damage-induced apoptosis were examined in promyelocytic leukemia cells, U937, in comparison with other differentiation-inducing agents to clarify the role of protein kinase C (PKC) vis-a-vis cellular differentiation in apoptosis. The apoptosis of U937 cells was observed at as early as 1–1.5 h following UV irradiation, with most cells being in apoptotic state at 3 h. Pretreatment with PMA for as short as 5 min was sufficient to inhibit apoptosis induced by UV irradiation, whereas apparent changes in cell cycle distributions and expression of differentiation markers by PMA were not observed until 12 h and 48 h, respectively. The inhibition of apoptosis by PMA was completely abolished by the pretreatment with calphostin C, a PKC inhibitor, and 4 alpha-phorbor 12,13-didecanoate, which is unable to activate PKC, did not protect U937 cells against apoptosis induced by UV irradiation. Other differentiation inducers, such as cyclic AMP and active vitamin D 3, did not affect the UV-induced apoptosis of U937 cells. Taken together, it was suggested that PMA inhibits DNA damage-induced apoptosis through the activation of PKC rather than as a result of differentiation of U937 cells.