Abstract
Luteolin (3',4',5,7-tetrahydroxyflavone), an edible flavonoid, has anti-melanoma
effects and inhibits AKT signaling. Activation of the PI3K/AKT pathway promotes
vemurafenib resistance in melanoma. Whether luteolin overcomes vemurafenib
resistance in melanoma is not known.
In this study, we found that luteolin inhibited the proliferation, migration, and colony formation of vemurafenib-resistant A375 melanoma (A375-VR) cells. We also found that luteolin dose-dependently restrained A375-VR melanoma growth in mice without observable toxicities. Network pharmacology predicted that PI3K/AKT signaling pathway was the top 1 pathway involved in the effects of luteolin in overcoming vemurafenib resistance in melanoma. Western blotting results showed that luteolin downregulated protein levels of phospho-Akt (Ser473), EGFR, AXL and IGF1-R, and BRAF (V600E), MEK1/2, Phospho-MEK1/2 (Ser217/221), ERK1/2, and phospho-ERK1/2 (Thr202/Tyr204) in A375-VR cells. EGFR, AXL and IGF1-R are receptor tyrosine kinases that can activate AKT. BRAF, MEK, and ERK are Akt’s downstream signaling molecules. These novel findings indicate that inhibition of the AKT signaling pathway is associated with the effects of luteolin in overcoming vemurafenib resistance in melanoma. This study suggests that luteolin has the potential to be developed into a safe and effective drug for treating vemurafenib-resistant melanomas.
effects and inhibits AKT signaling. Activation of the PI3K/AKT pathway promotes
vemurafenib resistance in melanoma. Whether luteolin overcomes vemurafenib
resistance in melanoma is not known.
In this study, we found that luteolin inhibited the proliferation, migration, and colony formation of vemurafenib-resistant A375 melanoma (A375-VR) cells. We also found that luteolin dose-dependently restrained A375-VR melanoma growth in mice without observable toxicities. Network pharmacology predicted that PI3K/AKT signaling pathway was the top 1 pathway involved in the effects of luteolin in overcoming vemurafenib resistance in melanoma. Western blotting results showed that luteolin downregulated protein levels of phospho-Akt (Ser473), EGFR, AXL and IGF1-R, and BRAF (V600E), MEK1/2, Phospho-MEK1/2 (Ser217/221), ERK1/2, and phospho-ERK1/2 (Thr202/Tyr204) in A375-VR cells. EGFR, AXL and IGF1-R are receptor tyrosine kinases that can activate AKT. BRAF, MEK, and ERK are Akt’s downstream signaling molecules. These novel findings indicate that inhibition of the AKT signaling pathway is associated with the effects of luteolin in overcoming vemurafenib resistance in melanoma. This study suggests that luteolin has the potential to be developed into a safe and effective drug for treating vemurafenib-resistant melanomas.
| Original language | English |
|---|---|
| Pages | 66 |
| Number of pages | 1 |
| Publication status | Published - 19 Nov 2022 |
| Event | 第七届可食和药用植物资源及功能成分国际学术研讨会 = 7th International Symposium on Edible & Medical Plant Resources and the Bioactive Ingredients, ISEPR 2022 - Urumqi, China Duration: 19 Nov 2022 → 19 Nov 2022 http://www.xjipc.cas.cn/tzggnew/202211/t20221116_6549481.html |
Symposium
| Symposium | 第七届可食和药用植物资源及功能成分国际学术研讨会 = 7th International Symposium on Edible & Medical Plant Resources and the Bioactive Ingredients, ISEPR 2022 |
|---|---|
| Country/Territory | China |
| City | Urumqi |
| Period | 19/11/22 → 19/11/22 |
| Internet address |
User-Defined Keywords
- Luteolin
- Melanoma
- Vemurafenib resistance
- Akt signaling