Heat shock proteins in the context of photodynamic therapy: autophagy, apoptosis and immunogenic cell death

Abstract

Photodynamic therapy (PDT) is an anti-tumor treatment administered for the elimination of early-stage malignancies and the palliation of symptoms in patients with late-stage tumors, which involves the activation of a photosensitizer (PS) using light of a specific wavelength, which also generates singlet oxygen and other reactive oxygen species (ROS) that cause tumor cell death. Several mechanisms are involved in the protective responses to PDT including the expression of chaperone/heat shock proteins (HSPs). The HSPs are a family of proteins that are induced by cells in response to exposure to stressful conditions. In the last few decades, it has been discovered that HSPs can play an important role in cell survival, due to the fact that they are responsible for many cytoprotective mechanisms. These proteins have different functions depending on their intracellular or extracellular location. In general, intracellular HSPs have been related to an anti-apoptotic function and recently, HSP-induced autophagy has shown to have a protective role in these chaperones. In contrast, extracellular HSPs or membrane-bound HSPs mediate immunological functions. In the present article, we attempt to review the current knowledge concerning the role of HSPs in the outcome of PDT in relation to autophagy and apoptosis mediated-resistance to photodynamic treatment. We will also discuss how certain PDT protocols optimally stimulate the immune system through HSPs.

AlPcS₄-PDT for gastric cancer therapy using gold nanorod, cationic liposome, and Pluronic^® F127 nanomicellar drug carriers

“…5,6 PDT has been brought into focus for its high efficiency, safety, small operational wound, few side effects, synergy compatibility, repeatability, relatively low cost, etc. 7,8 Under light activation, the photosensitizer generates reactive oxygen species (ROS) to induce oxidative stress, which can damage cellular organelles and membranes, thereby leading to apoptosis or necrosis of the neoplastic tissue. 5,9 Moreover, PDT leads to indirect tumor ablation by causing tumor ischemia and nutritional starvation through vascular leakage, blood flow stasis, and vascular collapse.…”

Avaliação De Proteínas De Choque Térmico Em Células Neoplásicas De Laringe (Hep-2) Após Tratamento Fotodinâmico

“…A presença de HSP70 pode inibir várias vias de morte celular, incluindo a apoptose intrínseca, levando a resistência à TFD (RODRÍGUEZ et al, 2016). Entretanto, a HSP70 pode se ligar ao fator indutor de apoptose (AIF), levando à inibição da apoptose independente de caspase (EVANS; CHANG; GESTWICKI, 2010).…”

“…Entretanto, a HSP70 pode se ligar ao fator indutor de apoptose (AIF), levando à inibição da apoptose independente de caspase (EVANS; CHANG; GESTWICKI, 2010). Na TFD é indutora de apoptose, tendo como uma das vias a translocação das HSP70 do citoplasma para a superfície celular, onde pode ser liberada no meio, como resposta do impacto da terapia, estando relacionada à ruptura mitocondrial ou estresse superficial direto, e sua a principal função é estabilizar a integridade da membrana plasmática (RODRÍGUEZ et al, 2016). No entanto, sob tratamento letal com TFD, a HSP70 não consegue prevenir a apoptose e, contrariamente, promove a morte celular imunogênica (GUO, 2004).…”

“…A inibição da HSP90 libera Apaf-1 para interagir com a caspase-9 e induzir a cascata apoptótica pela ativação da procaspase-3 (PANZARINI; INGUSCIO; DINI, 2013). Os inibidores de HSP90 estão sendo desenvolvidos como agentes anticancerígenos e mostraram bons resultados em tumores sólidos e algumas malignidades hematológicas (RODRÍGUEZ et al, 2016). Kim et al (2012), os resultados obtidos foram pró-tumorais, mostrando que a redução de HSP27 após TFD restaurou a sobrevivência celular por estimular a autofagia e atenuou a apoptose por inibir a via mediada por caspases.…”

Heat Shock Protein 60 in Hepatocellular Carcinoma: Insights and Perspectives

“…Furthermore, the anti-apoptotic actions of HSP60 involve its interaction with several molecules including the mitochondrial HSP70, survivin, and p53. HSP60 is also a potent regulator of the mitochondrial permeability transition which is meditated through a multichaperone complex comprising HSP60, HSP90, and tumor necrosis factor receptor-associated protein-1 (TNFRP1), particularly assembled in tumors but not in normal cells (Ghosh et al, 2010;Rodríguez et al, 2016) (Figure 2). In tumor cells, the anti-apoptotic HSP60 has been found to interact with cyclophilin D in the mitochondrial permeability transition pore where subsequent disruption of this interaction altered the mitochondrial permeability transition, stimulated caspasedependent apoptosis, and led to suppression of tumor cell growth (Ghosh et al, 2010).…”