Mitochondria-targeted prostate cancer therapy using a near-infrared fluorescence dye–monoamine oxidase A inhibitor conjugate

Lv, Qingzhi; Yang, Xiaoguang; Wang, Menglin; Yang, Jincheng; Qin, Zhilin; Kan, Qiming; Zhang, Haotian; Wang, Yongjun; Wang, Dun; Zhang, He

doi:10.1016/j.jconrel.2018.04.038

Cited by 39 publications

(42 citation statements)

References 30 publications

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“…MHI-148, IR-780, IR-783, and DZ-1) [6][7][8] are known for their tumor localizing properties [9][10][11][12]. Therefore, these Cy-7 dyes are potential carriers of cytotoxic payload for combined cancer targeted therapy and imaging [13][14][15][16]. Our research in this area, we happened to make a surprising finding regarding such conjugation process.…”

Section: Introductionmentioning

confidence: 87%

Site-Specific Labeling of Proteins with Near-IR Dyes

Lin¹,

Usama²,

Burgess³

2018

Preprint

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Convenient labeling of proteins is important for observing its function under physiological conditions.  In tissues particularly, heptamethine cyanine dyes (Cy-7) are valuable because they absorb in near infrared (NIR) region (750 – 900 nm) where light penetration is maximal.  In this work, we found Cy-7 dyes with a meso-Cl functionality covalently binding to proteins with free Cys residues under physiological conditions (aqueous environments, at near neutral pH, and 37 °C).  It transpired that the meso-Cl of the dye was displaced by free thiols in protein, while nucleophilic side-chains from amino acids like Tyr, Lys, and Ser did not react.  This finding shows a new possibility for convenient and selective labeling of proteins with near-IR fluorescent probes.

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Section: Introductionmentioning

confidence: 87%

Site-Specific Labeling of Proteins with Near-IR Dyes

Lin¹,

Usama²,

Burgess³

2018

Preprint

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“…Probes of this type, i.e., with a 1-chloro-2,6-disubstituted cyclohexane (i.e., MHI-148, IR-780, IR-783, and DZ-1) [ 6 , 7 , 8 ], are known for their tumor localizing properties [ 9 , 10 , 11 , 12 ]. Therefore, these Cy-7 dyes are potential carriers of cytotoxic payload for combined cancer targeted therapy and imaging [ 13 , 14 , 15 , 16 ]. In our research in this area, we happened to make a surprising finding regarding such a conjugation process.…”

Section: Introductionmentioning

confidence: 99%

Site-Specific Labeling of Proteins with Near-IR Heptamethine Cyanine Dyes

2018

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Convenient labeling of proteins is important for observing its function under physiological conditions. In tissues particularly, heptamethine cyanine dyes (Cy-7) are valuable because they absorb in the near-infrared (NIR) region (750–900 nm) where light penetration is maximal. In this work, we found Cy-7 dyes with a meso-Cl functionality covalently binding to proteins with free Cys residues under physiological conditions (aqueous environments, at near neutral pH, and 37 °C). It transpired that the meso-Cl of the dye was displaced by free thiols in protein, while nucleophilic side-chains from amino acids like Tyr, Lys, and Ser did not react. This finding shows a new possibility for convenient and selective labeling of proteins with NIR fluorescent probes.

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“… 26 Excitingly, a mitochondrial-targeting MAO-A inhibitor was synthesized and used to target prostate cancer, which dramatically inhibited tumour growth. 27 Our results first showed that expression of MAO-A was significantly increased in vivo in GC tissues compared with that observed in paired adjacent non-cancerous tissues. Moreover, the in vitro protein levels of MAO-A were shown to be higher in GC cell lines (AGS, MGC803) than in normal gastric epithelial cells (GES1).…”

Section: Discussionmentioning

confidence: 50%

<p>Monoamine Oxidase A is a Major Mediator of Mitochondrial Homeostasis and Glycolysis in Gastric Cancer Progression</p>

Chen¹,

Li²,

Sun³

et al. 2020

CMAR

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Objective: Monoamine oxidase A (MAO-A) is a mitochondrial protein involved in tumourigenesis in different types of cancer. However, the biological function of MAO-A in gastric cancer development remains unknown. Methods: We examined MAO-A expression in gastric cancer tissues and in gastric cancer cell lines by immunohistochemistry and Western blot analyses. CCK8, FACS and bromodeoxyuridine incorporation assays were performed to assess the effects of MAO-A on gastric cancer cell proliferation. The role of MAO-A in mitochondrial function was determined through MitoSOX Red staining, ATP generation and glycolysis assays. Results: In the present study, we observed that MAO-A was significantly upregulated in gastric cancer tissues and in AGS and MGC803 cells. The observed MAO-A inhibition indicated decreased cell cycle progression and proliferation. Silencing MAO-A expression was associated with suppressed migration and invasion of gastric cancer cells in vitro. Moreover, alleviated mitochondrial damage in these cells was demonstrated by decreased levels of mitochondrial reactive oxygen species and increased ATP generation. MAO-A knockdown also regulated the expression of the glycolysis rate-limiting enzymes hexokinase 2 and pyruvate dehydrogenase. Finally, we observed that the glycolysis-mediated effect was weakened in AGS and MGC803 cells when MAO-A was blocked. Conclusion: The findings of the present study indicate that MAO-A is responsible for mitochondrial dysfunction and aerobic glycolysis, which in turn leads to the proliferation and metastasis of human gastric tumour cells.

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Mitochondria-targeted prostate cancer therapy using a near-infrared fluorescence dye–monoamine oxidase A inhibitor conjugate

Cited by 39 publications

References 30 publications

Site-Specific Labeling of Proteins with Near-IR Dyes

Site-Specific Labeling of Proteins with Near-IR Dyes

Site-Specific Labeling of Proteins with Near-IR Heptamethine Cyanine Dyes

<p>Monoamine Oxidase A is a Major Mediator of Mitochondrial Homeostasis and Glycolysis in Gastric Cancer Progression</p>

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