Low-power laser irradiation activates Src tyrosine kinase through reactive oxygen species-mediated signaling pathway

ABSTRACT Src tyrosine kinases are central components of adhesive responses and are required for cell spreading onto the extracellular matrix. Among other intracellular messengers elicited by integrin ligation are reactive oxygen species, which act as synergistic mediators of cytoskeleton rearrangement and cell spreading. We report that after integrin ligation, the tyrosine kinase Src is oxidized and activated. Src displays an early activation phase, concurrent with focal adhesion formation and driven mainly by Tyr527 dephosphorylation, and a late phase, concomitant with reactive oxygen species production, cell spreading, and integrin-elicited kinase oxidation. In addition, our results suggest that reactive oxygen species are key mediators of in vitro and in vivo v-Src tumorigenic properties, as both antioxidant treatments and the oxidant-insensitive C245A and C487A Src mutants greatly decrease invasivity, serum-independent and anchorage-independent growth, and tumor onset. Therefore we propose that, in addition to the known phosphorylation/dephosphorylation circuitry, redox regulation of Src activity is required during both cell attachment to the extracellular matrix and tumorigenesis.

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780 nm low power diode laser irradiation stimulates proliferation of keratinocyte cultures: Involvement of reactive oxygen species

Lasers in Surgery and Medicine ◽

10.1002/(sici)1096-9101(1998)22:4<212::aid-lsm5>3.0.co;2-s ◽

1998 ◽

Vol 22 (4) ◽

pp. 212-218 ◽

Cited By ~ 175

Author(s):

Nili Grossman ◽

Naomi Schneid ◽

H. Reuveni ◽

S. Halevy ◽

R. Lubart

Keyword(s):

Reactive Oxygen Species ◽

Low Power ◽

Laser Irradiation ◽

Diode Laser ◽

Reactive Oxygen ◽

Oxygen Species ◽

Power Diode

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Photo-Responsive Supramolecular Micelles for Controlled Drug Release and Improved Chemotherapy

International Journal of Molecular Sciences ◽

10.3390/ijms22010154 ◽

2020 ◽

Vol 22 (1) ◽

pp. 154

Author(s):

Fasih Bintang Ilhami ◽

Kai-Chen Peng ◽

Yi-Shiuan Chang ◽

Yihalem Abebe Alemayehu ◽

Hsieh-Chih Tsai ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Drug Release ◽

Visible Light ◽

Cancer Cells ◽

Laser Irradiation ◽

Reactive Oxygen ◽

Controlled Drug Release ◽

Grand Challenge ◽

Supramolecular System ◽

Oxygen Species

Development of stimuli-responsive supramolecular micelles that enable high levels of well-controlled drug release in cancer cells remains a grand challenge. Here, we encapsulated the antitumor drug doxorubicin (DOX) and pro-photosensitizer 5-aminolevulinic acid (5-ALA) within adenine-functionalized supramolecular micelles (A-PPG), in order to achieve effective drug delivery combined with photo-chemotherapy. The resulting DOX/5-ALA-loaded micelles exhibited excellent light and pH-responsive behavior in aqueous solution and high drug-entrapment stability in serum-rich media. A short duration (1–2 min) of laser irradiation with visible light induced the dissociation of the DOX/5-ALA complexes within the micelles, which disrupted micellular stability and resulted in rapid, immediate release of the physically entrapped drug from the micelles. In addition, in vitro assays of cellular reactive oxygen species generation and cellular internalization confirmed the drug-loaded micelles exhibited significantly enhanced cellular uptake after visible light irradiation, and that the light-triggered disassembly of micellar structures rapidly increased the production of reactive oxygen species within the cells. Importantly, flow cytometric analysis demonstrated that laser irradiation of cancer cells incubated with DOX/5-ALA-loaded A-PPG micelles effectively induced apoptotic cell death via endocytosis. Thus, this newly developed supramolecular system may offer a potential route towards improving the efficacy of synergistic chemotherapeutic approaches for cancer.

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