Skin communicates what we deeply feel: antibiotic prophylactic treatment to reduce epidermal growth factor receptor inhibitors induced rash in lung cancer (the Pan Canadian rash trial)

Arrieta, Óscar; Carmona, Amir; Vega, María Teresa; Lopez-Mejia, Mariana; Cardona, Andrés F.

doi:10.21037/atm.2016.08.19

Cited by 1 publication

(1 citation statement)

References 23 publications

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“…Genetic polymorphism and serum level of TNF-α have been shown to be associated with sorafenib-induced HFSR [ 29 ]. TNF-α can induce inflammation and participate in the impairment of skin barrier function, which thus increases the sensitivity of skin to environmental insults [ 28 , 30 ]. Abnormal expression of matrix metalloproteinases such as MMP1 and MMP3 is known to affect the homeostasis of keratinocytes [ 31 , 32 , 33 ].…”

Section: Resultsmentioning

confidence: 99%

Identification of Beilschmiedia tsangii Root Extract as a Liver Cancer Cell–Normal Keratinocyte Dual-Selective NRF2 Regulator

et al. 2021

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Transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) plays a crucial role in regulating the expression of genes participating in cellular defense mechanisms against oxidative or xenobiotic insults. However, there is increasing evidence showing that hyperactivation of NRF2 is associated with chemoresistance in several cancers, including hepatocellular carcinoma (HCC), thus making NRF2 an attractive target for cancer therapy. Another important issue in cancer medication is the adverse effects of these substances on normal cells. Here, we attempted to identify a dual-selective NRF2 regulator that exerts opposite effects on NRF2-hyperactivated HCC cells and normal keratinocytes. An antioxidant response element driven luciferase reporter assay was established in Huh7 and HaCaT cells as high-throughput screening platforms. Screening of 3,000 crude extracts from the Taiwanese Indigenous Plant Extract Library resulted in the identification of Beilschmiedia tsangii (BT) root extract as a dual-selective NRF2 regulator. Multiple compounds were found to contribute to the dual-selective effects of BT extract on NRF2 signaling in two cell lines. BT extract reduced NRF2 protein level and target gene expression levels in Huh7 cells but increased them in HaCaT cells. Furthermore, notable combinatory cytotoxic effects of BT extract and sorafenib on Huh7 cells were observed. On the contrary, sorafenib-induced inflammatory reactions in HaCaT cells were reduced by BT extract. In conclusion, our results suggest that the combination of a selective NRF2 activator and inhibitor could be a practical strategy for fine-tuning NRF2 activity for better cancer treatment and that plant extracts or partially purified fractions could be a promising source for the discovery of dual-selective NRF2 regulators.

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