mTHPC-based photodynamic therapy induction of autophagy and apoptosis in cultured cells in relation to mitochondria and endoplasmic reticulum stress

Franï¿1⁄2ois, Aurï¿1⁄2lie

doi:10.3892/ijo.2011.1174

Cited by 19 publications

(27 citation statements)

References 39 publications

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“…results indicating a role of a p53-independent mechanism in response to PDT in p53-deficient cells (13). Both apoptosis and autophagy can occur after PDT (15), and recent studies described a non-apoptotic cell death associated with the induction of autophagy (2,3,15,16).…”

Section: Discussionmentioning

confidence: 89%

Photodynamic treatment induces cell death by apoptosis or autophagy depending on the melanin content in two B16 melanoma cell lines

Sparsa¹,

Bellaton²,

Naves³

et al. 2012

Oncology Reports

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Abstract. Photodynamic therapy (PDT) is now a well-established treatment modality for cutaneous carcinomas and is based on the administration of a light-activated drug followed by illumination of the pathological area. The treatment of metastatic melanoma remains a therapeutic challenge. To define the possible role of melanin in relative phototoxicity of 5-aminolevulinic acid (5-ALA), a photosensitizer used in PDT in vivo, we studied cell death in two variants (with or without melanin, B16F10 and B16G4F cells, respectively) of a melanoma cell line. Concentrations of 5-Ala up to 10 mM induced similar cytostatic effects in the B16G4F and B16F10 cells. PDT and high 5-ALA concentrations induced photocytotoxicity in both melanoma cell lines (at 10 mM for B16F10 cells and at 5 mM for B16G4F cells). Cell death corresponded to p53-dependent apoptotic signaling in pigmented B16F10 cells, whereas an autophagic response leading to a caspase-independent death was detected in nonpigmented B16G4F cells. Therefore, the PDT-induced cell death pathway appeared to correlate with melanin synthesis capacity in melanoma cells. To reduce the cytotoxicity of 5-ALA without irradiation, a low drug concentration could be used. Consequently, in combination with current therapeutics, a moderate concentration of 5-ALA and PDT may constitute a supplementary promising approach to eliminate metastatic melanoma. IntroductionPhotodynamic therapy (PDT) has been used in clinical application for many years, either systemically, or locally or topically applied to a patient bearing a lesion (cancerous or not). PDT with systemic photosensitizers has been used to treat a range of internal malignancies (lung and brain cancers) and for skin cancers (1). This cancer treatment is approved by many countries for the treatment of non-melanotic skin cancers such as basal cell carcinomas and Bowen's disease. PDT does not seem to be an appropriate treatment of melanotic melanoma in vivo, and several reasons can justify this low use. Almost all melanomas overexpress the classical ATP-binding cassette transporters (ABC protein family), leading to drug release into the extracellular medium and to the resistance by tumor cells. The antioxidant activity of melanoma is much higher than observed in other skin cancers (basal and squamous carcinomas) reducing the cytotoxic effect of ROS generated by PDT (2). Nearly all photosensitizers (PS) show a significant absorbance in ultraviolet (UV) wavelengths, while melanin absorbs a large portion of the light intended to activate PS. The light absorption by pigment strongly reduces its penetration into the tumor. Studies have been carried out with pigmented or amelanotic melanoma cells suggesting that amelanotic cells may be more susceptible to PDT (2). Among the molecules used in PDT, 5-aminolevulinic acid (5-ALA) is not itself a photosensitizer and instead it is used as a prodrug leading to the accumulation of protoporphyrin IX in the mitochondria inducing damage and subsequently cell death after light irradiation (3).It is w...

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Section: Discussionmentioning

confidence: 89%

Photodynamic treatment induces cell death by apoptosis or autophagy depending on the melanin content in two B16 melanoma cell lines

Sparsa¹,

Bellaton²,

Naves³

et al. 2012

Oncology Reports

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show abstract

“…PDT is used worldwide not only in the primary treatment for malignant and premalignant skin cancer but also for adjuvant treatment in lung, brain, esophageal, biliary and urinary tract cancer (2,(14)(15)(16). The rapid generation of ROS observed in PDT-treated cells has been reported to induce damage to mitochondria or the endoplasmic reticulum (ER) and lead to apoptosis (23,24). Although apoptosis has been reported as the predominant cell death modality after photosensitizermediated PDT, the mechanism of PDT-mediated cell death is largely unknown.…”

Section: Discussionmentioning

confidence: 99%

Pheophorbide a-mediated photodynamic therapy induces autophagy and apoptosis via the activation of MAPKs in human skin cancer cells

Yoon

Kim

et al. 2013

Oncology Reports

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Pheophorbide a (Pa), a chlorophyll derivative, is a photosensitizer that can induce significant antitumor effects in several types of tumor cells. The present study investigated the mechanism of Pa-mediated photodynamic therapy (Pa-PDT) in the human skin cancer cell lines A431 and G361. PDT significantly inhibited the cell growth in a Pa-concentration-dependent manner. We observed increased expression of Beclin-1, LC3B and ATG5, which are markers of autophagy, after PDT treatment in A431 cells but not in G361 cells. In G361 cells, Pa-PDT strongly induced PARP cleavage and subsequent apoptosis, which was confirmed using Annexin V/Propidium iodide double staining. Pa-PDT predominantly exhibited its antitumor effects via activation of ERK1/2 and p38 in A431 and G361 cells, respectively. An in vivo study using the CAM xenograft model demonstrated that Pa-PDT strongly induced autophagy and apoptosis in A431-transplanted tumors and/or apoptosis in G361-transplanted tumors. These results may provide a basis for understanding the underlying mechanisms of Pa-PDT and for developing Pa-PDT as a therapy for skin cancer.

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“…Autophagy in PDT plays a prosurvival role in apoptosis competent cells and a prodeath role in deficient ones (reviewed in Reiners et al [102]). Mitochondrial-, ER- and lysosomes-localized PSs are involved in PDT-induced autophagy [103,104,105]. …”

Section: Autophagy In Pdt-photosensitized Cellsmentioning

confidence: 99%

Autophagy Contributes to the Death/Survival Balance in Cancer PhotoDynamic Therapy

Inguscio

Panzarini

Dini

2012

Cells

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Autophagy is an important cellular program with a “double face” role, since it promotes either cell survival or cell death, also in cancer therapies. Its survival role occurs by recycling cell components during starvation or removing stressed organelles; when damage becomes extensive, autophagy provides another programmed cell death pathway, known as Autophagic Cell Death (ACD). The induction of autophagy is a common outcome in PhotoDynamic Therapy (PDT), a two-step process involving the irradiation of photosensitizer (PS)-loaded cancer cells. Upon tissue oxygen interaction, PS provokes immediate and direct Reactive Oxygen Species (ROS)-induced damage to Endoplasmic Reticulum (ER), mitochondria, plasma membrane, and/or lysosomes. The main biological effects carried out in cancer PDT are direct cytotoxicity to tumor cells, vasculature damage and induction of inflammatory reactions stimulating immunological responses. The question about the role of autophagy in PDT and its putative immunological impact is hotly controversial and largely studied in recent times. This review deals with the induction of autophagy in PDT protocols and its dual role, also considering its interrelationship with apoptosis, the preferential cell death program triggered in the photodynamic process.

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mTHPC-based photodynamic therapy induction of autophagy and apoptosis in cultured cells in relation to mitochondria and endoplasmic reticulum stress

Cited by 19 publications

References 39 publications

Photodynamic treatment induces cell death by apoptosis or autophagy depending on the melanin content in two B16 melanoma cell lines

Photodynamic treatment induces cell death by apoptosis or autophagy depending on the melanin content in two B16 melanoma cell lines

Pheophorbide a-mediated photodynamic therapy induces autophagy and apoptosis via the activation of MAPKs in human skin cancer cells

Autophagy Contributes to the Death/Survival Balance in Cancer PhotoDynamic Therapy

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