Resveratrol inhibits proliferation, promotes differentiation and melanogenesis in HT-144 melanoma cells through inhibition of MEK/ERK kinase pathway

Lei, Mingjun; Yang, Dong; Sun, Cheng-Yi; Zhang, Xianghong

doi:10.1016/j.micpath.2017.09.029

Cited by 22 publications

(14 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, some studies have suggested that RES ( 1 ) could be cytotoxic to melanin‐producing cells. Lei, Dong, Sun, and Zhang () found that RES ( 1 ) strongly inhibited the proliferation of HT‐144 human melanoma cells with an IC 50 of 5–10 μM. Similarly, Okura et al () found that RES ( 1 ) inhibited the growth of B16F1 mouse melanoma cells and NHEMb human epidermal melanocytes with IC 50 s of 27.1 and 38.2 μM, respectively, values that are comparable to those of hydroquinone (28.3 and 9.4 μM).…”

Section: Resultsmentioning

confidence: 90%

Tyrosinase‐catalyzed oxidation of resveratrol produces a highly reactive ortho‐quinone: Implications for melanocyte toxicity

Ito

Fujiki

Matsui

et al. 2019

Pigment Cell Melanoma Res

View full text Add to dashboard Cite

trans‐Resveratrol (3,5,4′‐trihydroxy‐trans‐stilbene, RES), a naturally occurring polyphenol, has recently attracted increased interest as a health‐beneficial agent. However, based on its p‐substituted phenol structure, RES is expected to be a substrate for tyrosinase and to produce a toxic o‐quinone metabolite. The results of this study demonstrate that the oxidation of RES by tyrosinase produces 4‐(3′,5′‐dihydroxy‐trans‐styrenyl)‐1,2‐benzoquinone (RES‐quinone), which decays rapidly to an oligomeric product (RES‐oligomer). RES‐quinone was identified after reduction to its corresponding catechol, known as piceatannol. RES‐quinone reacts with N‐acetylcysteine, a small thiol, to form a diadduct and a triadduct, which were identified by NMR and MS analyses. The production of a triadduct is not common for o‐quinones, suggesting a high reactivity of RES‐quinone. RES‐quinone also binds to bovine serum albumin through its cysteine residue. RES‐oligomer can oxidize GSH to GSSG, indicating its pro‐oxidant activity. These results suggest that RES could be cytotoxic to melanocytes due to the binding of RES‐quinone to thiol proteins.

show abstract

Section: Resultsmentioning

confidence: 90%

Tyrosinase‐catalyzed oxidation of resveratrol produces a highly reactive ortho‐quinone: Implications for melanocyte toxicity

Ito

Fujiki

Matsui

et al. 2019

Pigment Cell Melanoma Res

View full text Add to dashboard Cite

show abstract

“…Previous studies have similarly reported that RV can potentially prevent various malignancies through inhibiting cellular proliferation and regulating autophagy (22)(23)(24). In a study by Lei et al (25), RV decreased proliferation, enhanced cellular differentiation and improved melanin generation in HT-144 melanoma cells through inhibiting the mitogen-activated protein kinase kinase/ERK kinase pathway. Kim et al (26) revealed that RV triggered cell death in the mitochondrial pathway.…”

Section: Discussionmentioning

confidence: 95%

Resveratrol suppresses melanoma growth by promoting autophagy through inhibiting the PI3K/AKT/mTOR signaling pathway

Gong¹,

Xia²

2019

Exp Ther Med

View full text Add to dashboard Cite

Resveratrol (RV) is a natural polyphenolic phytoalexin derived from peanuts, red grape skins and red wine, and has been demonstrated to alleviate multiple types of malignancies. However, how RV achieves this in melanoma is unknown. The aim of present study was to investigate the role of RV in melanoma, using Cell Counting Kit-8, flow cytometry and western blot analysis. RV inhibited melanoma cell viability, migration and invasion counteracting melanoma progression. In addition, proteins associated with autophagy, including Beclin 1 and microtubule-associated protein 1A/1B-light chain 3 (LC3)-II/I, were upregulated, whereas p62 expression was downregulated in RV-treated cells. The number of LC3 + puncta, which can be applied to represent autophagosome formation, increased following RV treatment, suggesting that RV may trigger autophagy in melanoma cells. Treatment with the autophagy inhibitor, 3-methyladenine, reversed the RV-dependent inhibition of viability, migration and invasion of melanoma cells. RV treatment also reduced the ratios of phosphorylated (p)-AKT/AKT and p-mTOR/mTOR in melanoma cells. In conclusion, these findings suggested that RV may inhibit the viability and migration of melanoma cells through inhibiting the AKT/mTOR pathway, thus triggering autophagy. This indicated that RV may serve as an innovative therapeutic for melanoma treatment.

show abstract

“…For instance, Lei et al reported that resveratrol inhibited proliferation and promoted differentiation and melanogenesis in HT-144 melanoma cells through inhibition of MEK/ERK kinase pathway. 20 Research by Kim et al showed that res-veratrol induced mitochondrial apoptosis and inhibited cell invasion and migration by inhibiting epithelial–mesenchymal transition in oral squamous cell carcinoma cells. 21 Resvera-trol was also reported to decrease cell viability and proliferation while induced apoptosis in H460 lung cancer cells significantly.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol, an activator of SIRT1, induces protective autophagy in non-small-cell lung cancer via inhibiting Akt/mTOR and activating p38-MAPK

Wang

Cao

et al. 2018

OTT

128

View full text Add to dashboard Cite

BackgroundResveratrol, a natural polyphenolic phytoalexin, has potent anti-tumor activity. Recently, it was found to induce autophagy in cancer cells. However, the effects of resveratrol on autophagy in non-small-cell lung cancer (NSCLC) cells have not yet been clearly elucidated.Materials and methodsA549 and H1299 cells were treated with different concentrations of resveratrol. Cell growth and apoptosis were measured by CCK-8 assay and flow cytometry, respectively. A549 cells were then treated with 200 μM resveratrol or SRT1720. Cell autophagy was detected by western blot and immunofluorescence.ResultsIn this study, we found that resveratrol exerted the anti-tumor effect through inhibiting cell proliferation and promoting cell apoptosis in NSCLC cells dose-dependently. Resveratrol has also increased the relative expression of Beclin1 and LC3 II/I while decreased p62 expression, suggesting that resveratrol induced autophagy in NSCLC cells. In addition, resveratrol increased SIRT1 expression and SIRT1 activator SRT1720-induced autophagy of NSCLC cells. SIRT1 knockdown reduced resveratrol-induced autophagy significantly. These results indicated that resveratrol might induce autophagy through upregulating SIRT1 expression. Moreover, inhibiting autophagy by autophagy inhibitor 3-methyladenine or SIRT1 inhibitor nicotinamide significantly suppressed proliferation while promoted apoptosis compared with the resveratrol 200 μM group, suggesting that resveratrol-induced autophagy might act as a protective mechanism to promote NSCLC cell survival and inhibiting autophagy can enhance the anti-tumor effect of resveratrol. Besides that, resveratrol treatment inhibited Akt/mTOR while p38-MAPK was activated in NSCLC cells in a dose-dependent manner. Activating Akt/ mTOR pathway by IGF-1 or inhibiting p-38-MAPK pathway by doramapimod significantly inhibited cell proliferation while increased cell apoptosis of NSCLC cells compared with the resveratrol 200 μM group.ConclusionTaken together, our findings suggest that resveratrol inhibited proliferation but induced apoptosis and autophagy via inhibiting Akt/mTOR and activating p38-MAPK pathway. Resveratrol-induced autophagy might act as a protective mechanism to promote NSCLC cell survival. Therefore, inhibition of autophagy may enhance the anti-tumor activity of resveratrol in NSCLC.

show abstract

Resveratrol inhibits proliferation, promotes differentiation and melanogenesis in HT-144 melanoma cells through inhibition of MEK/ERK kinase pathway

Cited by 22 publications

References 23 publications

Tyrosinase‐catalyzed oxidation of resveratrol produces a highly reactive ortho‐quinone: Implications for melanocyte toxicity

Tyrosinase‐catalyzed oxidation of resveratrol produces a highly reactive ortho‐quinone: Implications for melanocyte toxicity

Resveratrol suppresses melanoma growth by promoting autophagy through inhibiting the PI3K/AKT/mTOR signaling pathway

Resveratrol, an activator of SIRT1, induces protective autophagy in non-small-cell lung cancer via inhibiting Akt/mTOR and activating p38-MAPK

Contact Info

Product

Resources

About