Mitochondrial pathway and endoplasmic reticulum stress participate in the photosensitizing effectiveness of <scp>AE</scp>‐<scp>PDT</scp> in <scp>MG</scp>63 cells

Li, Kai‐Ting; Chen, Qing; Da-wu, Wang; Duan, Qin‐Qin; Tian, Shengke; He, Juanwen; Ou, Yunsheng; Bai, Dingqun

doi:10.1002/cam4.895

Cited by 39 publications

(14 citation statements)

References 27 publications

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“…Because the subcellular localization of a photosensitizer can impact its mechanisms of action, we considered that the mitochondria-caspase pathway was probably involved in the apoptotic mechanism. It is well known that Bax and cleaved Caspase-3 (active Caspase-3) are pro-apoptotic proteins and Bcl-2 is an antiapoptotic protein[20-23]. As expected, Bax and cleaved Caspase-3 expression was significantly upregulated by YLG-1-PDT, while Bcl-2 expression exhibited the opposite results.…”

Section: Discussionsupporting

confidence: 69%

Effect of photodynamic therapy with (17R,18R)-2-(1-hexyloxyethyl)-2-devinyl chlorine E6 trisodium salt on pancreatic cancer cells in vitro and in vivo

Shen¹,

Cao²,

Sun³

et al. 2018

WJG

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AIMTo investigate the antitumor effects and underlying mechanisms of (17R,18R)-2-(1-hexyloxyethyl)-2-devinyl chlorine E6 trisodium salt (YLG-1)-induced photodynamic therapy (PDT) on pancreatic cancer in vitro and in vivo.METHODSYLG-1 is a novel photosensitizer extracted from spirulina. Its phototoxicity, cellular uptake and localization, as well as its effect on reactive oxygen species (ROS) production, apoptosis, and expression of apoptosis-associated proteins were detected in vitro. An in vivo imaging system (IVIS), the Lumina K imaging system, and mouse models of subcutaneous Panc-1-bearing tumors were exploited to evaluate the drug delivery pathway and pancreatic cancer growth in vivo.RESULTSYLG-1 was localized to the mitochondria, and the appropriate incubation time was 6 h. Under 650 nm light irradiation, YLG-1-PDT exerted a potent cytotoxic effect on pancreatic cancer cells in vitro, which could be abolished by the ROS scavenger N-acetyl-L-cysteine (NAC). The death mode caused by YLG-1-PDT was apoptosis, accompanied by upregulated Bax and cleaved Caspase-3 and decreased Bcl-2 expression. The results from the IVIS images suggested that the optimal administration route was intratumoral (IT) injection and that the best time to conduct YLG-1-PDT was 2 h post-IT injection. Consistent with the results in vitro, YLG-1-PDT showed great growth inhibition effects on pancreatic cancer cells in a mouse model.CONCLUSIONYLG-1 is a potential photosensitizer for pancreatic cancer PDT via IT injection, the mechanisms of which are associated with inducing ROS and promoting apoptosis.

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Section: Discussionsupporting

confidence: 69%

Effect of photodynamic therapy with (17R,18R)-2-(1-hexyloxyethyl)-2-devinyl chlorine E6 trisodium salt on pancreatic cancer cells in vitro and in vivo

Shen¹,

Cao²,

Sun³

et al. 2018

WJG

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“…In this view, the use of photodynamic therapy (PDT) as a co-adjuvant therapy for cancer treatment is increasingly being considered [ 26 , 27 ]. PDT has been successfully used to kill OS cells in vitro [ 28 , 29 , 30 , 31 , 32 , 33 , 34 ] and in vivo [ 35 , 36 , 37 ]. In a previous study, we successfully demonstrated the in vitro efficacy of PDT in OS cell lines by using porphyrin-loaded poly-methyl methacrylate nanoparticles [ 38 ].…”

Section: Introductionmentioning

confidence: 99%

Functionalized Keratin as Nanotechnology-Based Drug Delivery System for the Pharmacological Treatment of Osteosarcoma

Martella

Ferroni

Guerrini

et al. 2018

IJMS

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Osteosarcoma therapy might be moving toward nanotechnology-based drug delivery systems to reduce the cytotoxicity of antineoplastic drugs and improve their pharmacokinetics. In this paper, we present, for the first time, an extensive chemical and in vitro characterization of dual-loaded photo- and chemo-active keratin nanoparticles as a novel drug delivery system to treat osteosarcoma. The nanoparticles are prepared from high molecular weight and hydrosoluble keratin, suitably functionalized with the photosensitizer Chlorin-e6 (Ce6) and then loaded with the chemotherapeutic drug Paclitaxel (PTX). This multi-modal PTX-Ce6@Ker nanoformulation is prepared by both drug-induced aggregation and desolvation methods, and a comprehensive physicochemical characterization is performed. PTX-Ce6@Ker efficacy is tested on osteosarcoma tumor cell lines, including chemo-resistant cells, using 2D and 3D model systems. The single and combined contributions of PTX and Ce6 is evaluated, and results show that PTX retains its activity while being vehiculated through keratin. Moreover, PTX and Ce6 act in an additive manner, demonstrating that the combination of the cytostatic blockage of PTX and the oxidative damage of ROS upon light irradiation have a far superior effect compared to singularly administered PTX or Ce6. Our findings provide the proof of principle for the development of a novel, nanotechnology-based drug delivery system for the treatment of osteosarcoma.

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“…Several preclinical in vitro and in vivo studies in OS showed that PDT is able to induce apoptosis (activation of mitochondrial and/or caspase pathways, and/or ROS increase), autophagy (activation of ROS-Jnk signaling pathway) and/or to arrest cells at the G2/M phase, depending on PS employed (Table 4) [136,137,138,139,140,141,142,143,144,145,146,147,148]. In addition, PDT can be employed in combination with other biophysical stimuli: low-level light therapy (LLLT) combined with N-aspartyl chlorin e6-PDT (NPe6-PDT) to enhance the cytotoxicity in MG-63 cells by increasing ROS and ATP [149].…”

Section: Application Of Biophysical Therapies In Osteosarcomamentioning

confidence: 99%

Adjuvant Biophysical Therapies in Osteosarcoma

Carina

Costa

Sartori

et al. 2019

Cancers

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Osteosarcoma (OS) is a primary bone sarcoma, manifesting as osteogenesis by malignant cells. Nowadays, patients’ quality of life has been improved, however continuing high rates of limb amputation, pulmonary metastasis and drug toxicity, remain unresolved issues. Thus, effective osteosarcoma therapies are still required. Recently, the potentialities of biophysical treatments in osteosarcoma have been evaluated and seem to offer a promising future, thanks in this field as they are less invasive. Several approaches have been investigated such as hyperthermia (HT), high intensity focused ultrasound (HIFU), low intensity pulsed ultrasound (LIPUS) and sono- and photodynamic therapies (SDT, PDT). This review aims to summarize in vitro and in vivo studies and clinical trials employing biophysical stimuli in osteosarcoma treatment. The findings underscore how the technological development of biophysical therapies might represent an adjuvant role and, in some cases, alternative role to the surgery, radio and chemotherapy treatment of OS. Among them, the most promising are HIFU and HT, which are already employed in OS patient treatment, while LIPUS/SDT and PDT seem to be particularly interesting for their low toxicity.

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Mitochondrial pathway and endoplasmic reticulum stress participate in the photosensitizing effectiveness of AE‐PDT in MG63 cells

Cited by 39 publications

References 27 publications

Effect of photodynamic therapy with (17R,18R)-2-(1-hexyloxyethyl)-2-devinyl chlorine E6 trisodium salt on pancreatic cancer cells in vitro and in vivo

Effect of photodynamic therapy with (17R,18R)-2-(1-hexyloxyethyl)-2-devinyl chlorine E6 trisodium salt on pancreatic cancer cells in vitro and in vivo

Functionalized Keratin as Nanotechnology-Based Drug Delivery System for the Pharmacological Treatment of Osteosarcoma

Adjuvant Biophysical Therapies in Osteosarcoma

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