Potential Protective Effects of Ursolic Acid against Gamma Irradiation-Induced Damage Are Mediated through the Modulation of Diverse Inflammatory Mediators

Wang, Hong; Loke, Wan Khai; Chinnathambi, Arunachalam; Alharbi, Sulaiman Ali; Tang, Feng Ru; Sethi, Gautam

doi:10.3389/fphar.2017.00352

Cited by 22 publications

(28 citation statements)

References 84 publications

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“…It is well known today that oxidative and nitrosative stresses are potent pathogenic mechanisms contributing to gamma radiation-induced damage. Recent studies have proposed that gamma radiation significantly increased intracellular ROS and reactive nitrogen species formation [1,62]. Our results demonstrated that gamma irradiation with 20 Gy significantly decreased cell viability in keratinocytes, accompanied by increased ROS production and NO release and decreased GSH levels.…”

Section: Discussionsupporting

confidence: 61%

“…The regulation of the NF-κB pathway is involved in the survival and death of cells exposed to gamma radiation [48]. Our previous study indicated that gamma radiation exposure timeand dose-dependently enhanced NF-κB DNA binding activities in HaCaT cells [62], while celastrol treatment was found to suppress this increase. Our observations were in agreement with a recent study [48].…”

Section: Discussionmentioning

confidence: 97%

“…Our previous study has demonstrated that gamma irradiation dose-(10 to 40 Gy) and time-(24 to 96 h) dependently decreased cell viability in HaCaT cells [62]. Twenty-four hours post-treatment with 1 and 1.5 µM celastrol after irradiation with 20 Gy significantly reversed the irradiation-induced cell viability decrease ( Figure 1B), while treatment with 0.5 to 2 µM celastrol did not influence cell viability in HaCaT cells without radiation exposure ( Figure 1A).…”

Section: Celastrol Dose-dependently Reversed Gamma Irradiation-inducementioning

confidence: 97%

“…HaCaT and BJ cells were obtained and maintained as previously described [62]. HaCaT cells were provided by Dr. Francoise Thierry, Institute of Medical Biology, Agency for Science Technology and Research (A*STAR), Singapore.…”

Section: Cell Linesmentioning

confidence: 99%

“…An EIA kit for 8-OH-dG detection was used to evaluate DNA damage as previously described [62]. Briefly, cells were harvested by trypsinization.…”

Section: Dna Oxidative Damage Assaymentioning

confidence: 99%

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Celastrol Alleviates Gamma Irradiation-Induced Damage by Modulating Diverse Inflammatory Mediators

Wang

Ahn

Alharbi

et al. 2020

IJMS

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The present study aimed to explore the possible radioprotective effects of celastrol and relevant molecular mechanisms in an in vitro cell and in vivo mouse models exposed to gamma radiation. Human keratinocytes (HaCaT) and foreskin fibroblast (BJ) cells were exposed to gamma radiation of 20 Gy, followed by treatment with celastrol for 24 h. Cell viability, reactive oxygen species (ROS), nitric oxide (NO) and glutathione (GSH) production, lipid peroxidation, DNA damage, inflammatory cytokine levels, and NF-κB pathway activation were examined. The survival rate, levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in blood, and p65 and phospho-p65 expression were also evaluated in mice after exposure to gamma radiation and celastrol treatment. The gamma irradiation of HaCaT cells induced decreased cell viability, but treatment with celastrol significantly blocked this cytotoxicity. Gamma irradiation also increased free radical production (e.g., ROS and NO), decreased the level of GSH, and enhanced oxidative DNA damage and lipid peroxidation in cells, which were effectively reversed by celastrol treatment. Moreover, inflammatory responses induced by gamma irradiation, as demonstrated by increased levels of IL-6, TNF-α, and IL-1β, were also blocked by celastrol. The increased activity of NF-κB DNA binding following gamma radiation was significantly attenuated after celastrol treatment. In the irradiated mice, treatment with celastrol significantly improved overall survival rate, reduced the excessive inflammatory responses, and decreased NF-κB activity. As a NF-κB pathway blocker and antioxidant, celastrol may represent a promising pharmacological agent with protective effects against gamma irradiation-induced injury.

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Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 97%

Section: Celastrol Dose-dependently Reversed Gamma Irradiation-inducementioning

confidence: 97%

Section: Cell Linesmentioning

confidence: 99%

“…An EIA kit for 8-OH-dG detection was used to evaluate DNA damage as previously described [62]. Briefly, cells were harvested by trypsinization.…”

Section: Dna Oxidative Damage Assaymentioning

confidence: 99%

See 3 more Smart Citations

Celastrol Alleviates Gamma Irradiation-Induced Damage by Modulating Diverse Inflammatory Mediators

Wang

Ahn

Alharbi

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

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Targeting autophagy using natural compounds for cancer prevention and therapy

Deng

Shanmugam

Kumar

et al. 2019

Cancer

266

188

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Autophagy, also known as macroautophagy, is a tightly regulated process involved in the stress responses, such as starvation. It is a vacuolar, lysosomal pathway for the degradation of damaged proteins and organelles in eukaryotic cells. Autophagy also plays a key role in various tissue processes and immune responses and in the regulation of inflammation. Over the past decade, three levels of autophagy regulation have been identified in mammalian cells: 1) signaling, 2) autophagosome formation, and 3) autophagosome maturation and lysosomal degradation. Any deregulation of the autophagy processes can lead to the development of diverse chronic diseases, such as diabetes, obesity, cardiovascular disease, neurodegenerative disease, and malignancies. However, the potential role of autophagy in cancer is rather complex and has been associated with both the induction and the inhibition of neoplasia. Several synthetic autophagy modulators have been identified as promising candidates for cancer therapy. In addition, diverse phytochemicals derived from natural sources, such as curcumin, ursolic acid, resveratrol, thymoquinone, and γ‐tocotrienol, also have attracted attention as promising autophagy modulators with minimal side effects. In this review, the authors discuss the importance of autophagy regulators and various natural compounds that induce and/or inhibit autophagy in the prevention and therapy of cancer.

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