The Role of Protein Kinase C Activity in the Killing of Chinese Hamster Ovary Cells by Ionizing Radiation and Photodynamic Treatment

Abstract

In several recent studies it has been shown that protein kinase C (PKC) activity may either potentiate or antagonize cell killing by different cytotoxic agents. These apparently conflicting observations suggest that the effects of PKC activity on cell survival may depend on the different properties of different cell types but do not exclude the possibility that the effects may also depend on the nature of the cytotoxic agent. In this context the effects of PKC activation and PKC inhibition or down-regulation on Chinese hamster ovary (CHO) cell survival after photodynamic treatment and ionizing radiation were studied. It appeared that PKC activation by short-term incubation with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) protected CHO cells against ionizing radiation but, in contrast, sensitized the cells to photodynamic treatment. Conversely, inhibition of PKC by H7 and down-regulation of PKC activity by prolonged incubation with TPA sensitized CHO cells to ionizing radiation but protected the cells against photodynamic treatment. These results demonstrate that in one particular cell type PKC activity may have opposite effects on cell survival following cellular damage, depending on the nature of the cytotoxic agent.

Decreased Efficiency of Trypsinization of Cells Following Photodynamic Therapy: Evaluation of a Role for Tissue Transglutaminase¶

“…However, this may be related to the localization of the photosensitizer at the time of treatment because there was no resistance to trypsinization reported using zinc tetra-hydroxyphthalocyanine (38) or HpD (39) following extended incubation protocols. More recently, photosensitization has been linked to the activation of a number of signaling events, such as increase in intracellular calcium (40), phospholipase activation (41), release of arachidonic metabolites (42) and activation of protein kinase-C (43). These primary signaling events can trigger further cascades, which may ultimately alter the overall topology of the cell, resulting in increased adhesion (44).…”

Direct tumor damage mechanisms of photodynamic therapy.

“…DAG activates protein kinase C (PKC), which is engaged in the induction of cell death or survival (Almeida et al, 2004). At least in two different cell lines inhibition of PKC resulted in an increase in cell survival following PDT (Agarwal et al, 1993;Rasch et al, 1997). However, the role of PKC in the cellular response to PDT remains controversial, as in another study inhibition of this kinase resulted in augmentation of cell death following PDT (Zhuang et al, 1998).…”

Heme oxygenase-1 protects tumor cells against photodynamic therapy-mediated cytotoxicity

“…Additionally, to some extent, PDT is also antagonized by cellular antioxidant defense mechanisms, including the glutathione system, manganese superoxide dismutase (Mn-SOD), catalase or lipoamide dehydrogenase (Kliukiene et al, 1997; Golab et al, 2003; Dolgachev et al, 2005; Oberdanner et al, 2005). Other mechanisms that protect tumor cells against PDT-mediated damage include stabilization of hypoxia-inducible factor alpha (Ferrario et al, 2000; Koukourakis et al, 2001), activity of antiapoptotic Bcl-2 proteins (Granville et al, 1999; Srivastava et al, 2001), induction of cyclooxygenases-2 (COX-2) (Ferrario et al, 2002; Hendrickx et al, 2003), activation of several signal transduction pathways including protein kinase C (Rasch et al, 1997), Etk/Bmx tyrosine kinase (Xue et al, 1999) or protein kinase B (PKB/Akt) (Zhuang and Kochevar, 2003).…”