Myricetin can control metastasis and invasion by suppressing ATF2-related signaling pathway in Rapamycin-resistant HepG2 hepatocellular cancer cells

Ömer Erdoğan; Özge Çevik

Myricetin can control metastasis and invasion by suppressing ATF2-related signaling pathway in Rapamycin-resistant HepG2 hepatocellular cancer cells

Abstract

Hepatocellular carcinoma continues to be one of the major health problems. One of the most important challenges in the treatment of hepatocellular cancer is gaining resistance to chemotherapy. Therefore, there is an urgent need for discoveries of naturally occurring antitumor compounds in the diet and to elucidate the anticancer mechanisms of action of existing dietary origin compounds. Myricetin is a dietary flavonoid and its antitumor activity is reported. In this study, HepG2 cells were incubated with 100 nM rapamycin for 6 weeks to develop rapamycin resistance. 10, 100, 250 and 500 µM myricetin was applied to rapamycin resistant HepG2 human hepatocellular cancer cells (HepG2-RR) for 24 and 48 hours. Changes in ATF2, SMAD3, SMAD4 and Col1A1 expressions of HepG2-RR cells after myricetin application were evaluated by Western blot and qPCR analysis. In addition, the effect of myricetin treatment on the migration/invasion of HepG2-RR cells was specified using the BD 24-well Boyden chamber. The IC50 values of rapamycin and myricetin on HepG2 cells for 48 hours incubation was calculated as 89,03±6,14 nM and 126,25±7,32 µM, respectively. On the other hand, we found that HepG2-RR cells treated with myricetin decreased cell proliferation, invasion, and migration by reducing the expression of ATF2, SMAD3, SMAD4, and Col1A1. As a result, we were shown that myricetin administration inhibited cell growth and cell migration by suppressing ATF2 in hepatocellular carcinoma cells that gained drug resistance.

Keywords

References

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Details

Primary Language

English

Subjects

Pharmaceutical Biochemistry

Journal Section

Research Article

Authors

Ömer Erdoğan
Türkiye

Özge Çevik
Türkiye

Publication Date

June 27, 2025

Submission Date

January 13, 2023

Acceptance Date

February 13, 2023

Published in Issue

Year 2023 Volume: 27 Number: 2

IZ

https://izlik.org/JA65PX25ZX

Cite

RIS / Bibtex

APA

Erdoğan, Ö., & Çevik, Ö. (2025). Myricetin can control metastasis and invasion by suppressing ATF2-related signaling pathway in Rapamycin-resistant HepG2 hepatocellular cancer cells. Journal of Research in Pharmacy, 27(2), 557-565. https://izlik.org/JA65PX25ZX

AMA

1.Erdoğan Ö, Çevik Ö. Myricetin can control metastasis and invasion by suppressing ATF2-related signaling pathway in Rapamycin-resistant HepG2 hepatocellular cancer cells. J. Res. Pharm. 2025;27(2):557-565. https://izlik.org/JA65PX25ZX

Chicago

Erdoğan, Ömer, and Özge Çevik. 2025. “Myricetin Can Control Metastasis and Invasion by Suppressing ATF2-Related Signaling Pathway in Rapamycin-Resistant HepG2 Hepatocellular Cancer Cells”. Journal of Research in Pharmacy 27 (2): 557-65. https://izlik.org/JA65PX25ZX.

EndNote

Erdoğan Ö, Çevik Ö (June 1, 2025) Myricetin can control metastasis and invasion by suppressing ATF2-related signaling pathway in Rapamycin-resistant HepG2 hepatocellular cancer cells. Journal of Research in Pharmacy 27 2 557–565.

IEEE

[1]Ö. Erdoğan and Ö. Çevik, “Myricetin can control metastasis and invasion by suppressing ATF2-related signaling pathway in Rapamycin-resistant HepG2 hepatocellular cancer cells”, J. Res. Pharm., vol. 27, no. 2, pp. 557–565, June 2025, [Online]. Available: https://izlik.org/JA65PX25ZX

ISNAD

Erdoğan, Ömer - Çevik, Özge. “Myricetin Can Control Metastasis and Invasion by Suppressing ATF2-Related Signaling Pathway in Rapamycin-Resistant HepG2 Hepatocellular Cancer Cells”. Journal of Research in Pharmacy 27/2 (June 1, 2025): 557-565. https://izlik.org/JA65PX25ZX.

JAMA

1.Erdoğan Ö, Çevik Ö. Myricetin can control metastasis and invasion by suppressing ATF2-related signaling pathway in Rapamycin-resistant HepG2 hepatocellular cancer cells. J. Res. Pharm. 2025;27:557–565.

MLA

Erdoğan, Ömer, and Özge Çevik. “Myricetin Can Control Metastasis and Invasion by Suppressing ATF2-Related Signaling Pathway in Rapamycin-Resistant HepG2 Hepatocellular Cancer Cells”. Journal of Research in Pharmacy, vol. 27, no. 2, June 2025, pp. 557-65, https://izlik.org/JA65PX25ZX.

Vancouver

1.Ömer Erdoğan, Özge Çevik. Myricetin can control metastasis and invasion by suppressing ATF2-related signaling pathway in Rapamycin-resistant HepG2 hepatocellular cancer cells. J. Res. Pharm. [Internet]. 2025 Jun. 1;27(2):557-65. Available from: https://izlik.org/JA65PX25ZX