Crosstalk between p38 MAPK and caspase-9 regulates mitochondria-mediated apoptosis induced by tetra-α-(4-carboxyphenoxy) phthalocyanine zinc photodynamic therapy in LoVo cells
- Yu Wang
- Chunhui Xia
- Zhiqiang Lun
- Yanxin Lv
- Wei Chen
- Tao Li
Published online on: November 2, 2017
Copyright: © Wang et al.
This is an open access article distributed under the terms of Creative Commons Attribution License.
Photodynamic therapy (PDT) is considered to be an advancing antitumor technology. PDT using hydrophilic/lipophilic tetra‑α-(4-carboxyphenoxy) phthalocyanine zinc (TαPcZn-PDT) has exhibited antitumor activity in Bel-7402 hepatocellular cancer cells. However, the manner in which p38 MAPK and caspase-9 are involved in the regulation of mitochondria-mediated apoptosis in the TαPcZn-PDT-treated LoVo human colon carcinoma cells remains unclear. Therefore, in the present study, a siRNA targeting p38 MAPK (siRNA-p38 MAPK) and the caspase‑9 specific inhibitor z-LEHD-fmk were used to examine the crosstalk between p38 MAPK and caspase-9 during mitochondria-mediated apoptosis in the TαPcZn-PDT‑treated LoVo cells. The findings revealed that the TαPcZn-PDT treatment of LoVo cells resulted in the induction of apoptosis, the formation of p38 MAPK/caspase-9 complexes, the activation of p38 MAPK, caspase-9, caspase-3 and Bid, the downregulation of Bcl-2, the reduction of mitochondrial membrane potential (ΔΨm), the upregulation of Bax and the release of apoptosis-inducing factor (AIF) and cytochrome c (Cyto c). By contrast, siRNA‑p38 MAPK or z-LEHD-fmk both attenuated the effects of TαPcZn-PDT in the LoVo cells. Furthermore, the results revealed that siRNA-p38 MAPK had more significant inhibitory effects on apoptosis and mitochondria compared with the effects of z-LEHD-fmk in TαPcZn-PDT-treated LoVo cells. These findings indicated that p38 MAPK plays the major regulatory role in the crosstalk between p38 MAPK and caspase-9 and that direct interaction between p38 MAPK and caspase-9 may regulate mitochondria-mediated apoptosis in the TαPcZn-PDT-treated LoVo cells.