Parallel damage in mitochondria and lysosomes is an efficient way to photoinduce cell death

Martins, Waleska K.; Santos, Nayra Fernandes; Rocha, Cleidiane de Sousa; Bacellar, Isabel O. L.; Tsubone, Tayana Mazin; Viotto, Ana Cláudia; Matsukuma, Adriana Y.; Abrantes, Aline Bianca de Paiva; Siani, Paulo; Dias, Luís Gustavo; Baptista, Maurı́cio S.

doi:10.1080/15548627.2018.1515609

Cited by 127 publications

(121 citation statements)

References 103 publications

(166 reference statements)

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“…This method basically responds to the mitochondrial activity, which supposedly suffers a direct impact by DMMB photosensitization (12). The half-maximum inhibitory concentration (IC 50 ) at 24 h was~10 nM DMMB/light, which is equivalent to the IC 50 found in other cell lines (12). Note also that there is no difference in the viability among the three cell lines tested (Fig.…”

Section: Dmmb Phototoxicity and P53 Functionmentioning

confidence: 86%

“…We noted that DMMB photoactivation results in a small percentage of cells stained with PI and there was no difference between cell lines. This is indeed expected, since the cell death mechanism induced by DMMB at nanomolar concentration is not necrosis, but, instead, autophagy-associated cell death (12). In order to have a positive control of necrotic cell death, we raised the DMMB concentration to 200 nM.…”

Section: Dmmb Phototoxicity and P53 Functionmentioning

confidence: 92%

“…Cell viability by MTT assay was used to estimate the proportion of viable cells at 24 h after photosensitization. This method basically responds to the mitochondrial activity, which supposedly suffers a direct impact by DMMB photosensitization (12). The half-maximum inhibitory concentration (IC 50 ) at 24 h was~10 nM DMMB/light, which is equivalent to the IC 50 found in other cell lines (12).…”

Section: Dmmb Phototoxicity and P53 Functionmentioning

confidence: 99%

“…Indeed, previous work of our laboratory has shown that photoactivation of DMMB kills cells at two orders of magnitude lower concentration than that of MB, because it targets selectively mitochondria and lysosomes, inducing a typical profile of autophagy-associated cell death (12). In contrast, MB kills cells by causing a general disturbance of redox homeostasis, triggering a variety of cell death mechanisms (12). At 10-20 nM range, DMMB strongly decreases the mitochondrial transmembrane inner potential, by approximately 50%, followed by an increase in cytosolic cathepsin B activity (12).…”

Section: Introductionmentioning

confidence: 96%

“…Although not frequently used in clinics, DMMB distinguishes itself from MB by its stronger interaction with membranes, photo-inducing liposome permeabilization a lot more efficiently than its parental compound (12,32). Indeed, previous work of our laboratory has shown that photoactivation of DMMB kills cells at two orders of magnitude lower concentration than that of MB, because it targets selectively mitochondria and lysosomes, inducing a typical profile of autophagy-associated cell death (12). In contrast, MB kills cells by causing a general disturbance of redox homeostasis, triggering a variety of cell death mechanisms (12).…”

Section: Introductionmentioning

confidence: 99%

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p53‐Dependent and p53‐Independent Responses of Cells Challenged by Photosensitization

Abrantes

Dias

Souza-Pinto

et al. 2018

Photochem & Photobiology

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The p53 protein exerts fundamental roles in cell responses to a variety of stress stimuli. It has clear roles in controlling cell cycle, triggering apoptosis, activating autophagy and modulating DNA damage response. Little is known about the role of p53 in autophagy‐associated cell death, which can be induced by photoactivation of photosensitizers within cells. The photosensitizer 1,9‐dimethyl methylene blue (DMMB) within nanomolar concentration regimes has specific intracellular targets (mitochondria and lysosomes), photoinducing a typical scenario of cell death with autophagy. Importantly, in consequence of its subcellular localization, photoactive DMMB induces selective damage to mitochondrial DNA, saving nuclear DNA. By challenging cells having different p53 protein levels, we investigated whether p53 modulates DMMB/light‐induced phototoxicity and cell cycle dynamics. Cells lacking p53 activity were slightly more resistant to photoactivated DMMB, which was correlated with a smaller sub‐G1 population, indicative of a lower level of apoptosis. DMMB photosensitization seems to induce mostly autophagy‐associated cell death and S‐phase cell cycle arrest with replication stress. Remarkably, these responses were independent on the p53 status, indicating that p53 is not involved in either process. Despite describing some p53‐related responses in cells challenged by photosensitization, our results also provide novel information on the consequences of DMMB phototoxicity.

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Section: Dmmb Phototoxicity and P53 Functionmentioning

confidence: 86%

Section: Dmmb Phototoxicity and P53 Functionmentioning

confidence: 92%

Section: Dmmb Phototoxicity and P53 Functionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

p53‐Dependent and p53‐Independent Responses of Cells Challenged by Photosensitization

Abrantes

Dias

Souza-Pinto

et al. 2018

Photochem & Photobiology

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Photodynamic Therapy Directed by Three‐Photon Active Rigid Plane Organic Photosensitizer

Cao

Fang

Liu

et al. 2020

Adv Healthcare Materials

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Multi‐photon photosensitizers (PSs) could significantly improve the efficacy of photodynamic therapy due to the long‐wavelength favorability for deeper tissue penetration and lower biological damage. However, most studies are limited to single‐photon or two‐photon PSs at a relatively short‐wave excitation window. To overcome this barrier, we rationally design a series of rigid plane compounds with efficient reactive oxygen species (ROS) production in vitro under laser irradiation. Furthermore, the studies show that one of the compounds (U‐TsO) could induce rapid multi‐types of cell death under three‐photon exposure, suggesting a promising clinical outcome in ex vivo 3D multicellular tumor spheroid. This work offers a novel strategy to construct functional materials with competitive multi‐photon photodynamic therapy (PDT) outcome.

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Time Rules the Efficacy of Immune Checkpoint Inhibitors in Photodynamic Therapy

Chen

et al. 2022

Advanced Science

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Lack of adequate effector T cells infiltrated in tumor isone of the main problems in the failure of immune checkpoint blockade therapy (ICBT). Photodynamic therapy (PDT) induced acute inflammation can sensitize tumors and activate T cells, thus assisting immune checkpoint inhibitors (ICI) against tumor growth and metastasis. T cells maturation and activation lag 3 to 7 days behind PDT. However, such timing in the combination therapy of ICI and PDT is commonly ignored in designing numerous multi-functional integrated nanomedicines. Herein, the authors illustrate that intervention timing of ICI after PDT affects the anti-tumor efficacy. A tumor-targeting nanomedicine is prepared by encapsulating indocyanine green into CD44 specifically binding material, a hyaluronic acid conjugated lipid poly(ethylene glycol). The PDT nanomedicine is designed to induce a robust immune response in tumor. The optimal group (Combo-STAR), ICI gave 5 days after PDT, significantly suppresses local tumor growth and eliminates metastasis. What should be highlighted is the time point of administration because if ICI is given too early, T cells are immature, otherwise, T cells are exhausted if ICI is given too late. This work presents theoretical guidance for raising awareness of intervention timing when augmenting ICBT with immune response inducers in clinic.

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Parallel damage in mitochondria and lysosomes is an efficient way to photoinduce cell death

Cited by 127 publications

References 103 publications

p53‐Dependent and p53‐Independent Responses of Cells Challenged by Photosensitization

p53‐Dependent and p53‐Independent Responses of Cells Challenged by Photosensitization

Photodynamic Therapy Directed by Three‐Photon Active Rigid Plane Organic Photosensitizer

Time Rules the Efficacy of Immune Checkpoint Inhibitors in Photodynamic Therapy

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