BACKGROUND AND OBJECTIVE: It has been reported that 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH)-mediated photodynamic therapy (PDT) effects on antitumor. However, it remains unclear whether gap junction (GJ) acts on phototoxicity of HPPH and which pathways are involved in the process. MATERIALS AND METHODS: We determine the effect of HPPH on cancer cell viability and the apoptosis-associated signaling by cell viability assay, reactive oxygen species (ROS) measurement, and caspase-3 activity assay. RESULTS: Our study uniquely showed that there is a strong correlation between GJ and HPPH-PDT cytotoxicity, that inhibition of GJ function in U87 cells by tetradecanoylphorbol-13-aaetate or carbenoxolone reduces HPPH-PDT cytotoxicity, that and the enhancement of GJ function by retinoid acid in U87 cells increases HPPH-PDT cytotoxicity. We also observed that GJ intercellular communication composed of connexin 32 (Cx32) induced by doxycycline in Hela cells enhances HPPH-PDT phototoxicity. In addition, we indicated that GJ prompts the HPPH-induced apoptosis likely due to the "bystander effect" of passing apoptotic signals between cells, which results in improving the accumulation of ROS, which also amplifies mitochondria depolarization and the activation of caspase-3. CONCLUSION: GJ enhances the efficacy of HPPH-PDT in U87 and Hela; GJ augments ROS production, which enhances the loss of mitochondrial membrane potential and the activation of caspase-3, and increases apoptosis in the tumor cells induced by HPPH-PDT. Our findings provide a basis for further development of GJ as a potential prediction of the efficacy of photodynamic therapy.
BACKGROUND AND OBJECTIVE: It has been reported that 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH)-mediated photodynamic therapy (PDT) effects on antitumor. However, it remains unclear whether gap junction (GJ) acts on phototoxicity of HPPH and which pathways are involved in the process. MATERIALS AND METHODS: We determine the effect of HPPH on cancer cell viability and the apoptosis-associated signaling by cell viability assay, reactive oxygen species (ROS) measurement, and caspase-3 activity assay. RESULTS: Our study uniquely showed that there is a strong correlation between GJ and HPPH-PDT cytotoxicity, that inhibition of GJ function in U87 cells by tetradecanoylphorbol-13-aaetate or carbenoxolone reduces HPPH-PDT cytotoxicity, that and the enhancement of GJ function by retinoid acid in U87 cells increases HPPH-PDT cytotoxicity. We also observed that GJ intercellular communication composed of connexin 32 (Cx32) induced by doxycycline in Hela cells enhances HPPH-PDT phototoxicity. In addition, we indicated that GJ prompts the HPPH-induced apoptosis likely due to the "bystander effect" of passing apoptotic signals between cells, which results in improving the accumulation of ROS, which also amplifies mitochondria depolarization and the activation of caspase-3. CONCLUSION: GJ enhances the efficacy of HPPH-PDT in U87 and Hela; GJ augments ROS production, which enhances the loss of mitochondrial membrane potential and the activation of caspase-3, and increases apoptosis in the tumor cells induced by HPPH-PDT. Our findings provide a basis for further development of GJ as a potential prediction of the efficacy of photodynamic therapy.