Myricetin induces apoptosis through the MAPK pathway and regulates JNK‑mediated autophagy in SK‑BR‑3 cells

Han,So-Hee; Lee,Jae-Han; Woo,Joong-Seok; Jung,Gi-Hwan; Jung,Soo-Hyun; Han,Eun-Ji; Park,Young-Seok; Kim,Byeong-Soo; Kim,Sang-Ki; Park,Byung-Kwon; Choi,Changsun; Jung,Ji-Youn

doi:10.3892/ijmm.2022.5110

Myricetin induces apoptosis through the MAPK pathway and regulates JNK‑mediated autophagy in SK‑BR‑3 cells

Authors:
- So-Hee Han
- Jae-Han Lee
- Joong-Seok Woo
- Gi-Hwan Jung
- Soo-Hyun Jung
- Eun-Ji Han
- Young-Seok Park
- Byeong-Soo Kim
- Sang-Ki Kim
- Byung-Kwon Park
- Changsun Choi
- Ji-Youn Jung
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Affiliations: Department of Companion and Laboratory Animal Science, Kongju National University, Yesan-eup, Chungcheongnamdo 32439, Republic of Korea, School of Food Science and Technology, Chung‑ang University, Ansung, Gyeonggi-do 17546, Republic of Korea
Published online on: February 25, 2022 https://doi.org/10.3892/ijmm.2022.5110
Article Number: 54
Copyright: © Han et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Myricetin, a flavonoid found in fruits and vegetables, is known to have antioxidant and anticancer effects. However, the anticancer effects of myricetin on SK‑BR‑3 human breast cancer cells have not been elucidated. In the present study, the anticancer effects of myricetin were confirmed in human breast cancer SK‑BR‑3 cells. As the concentration of myricetin increased, the cell viability decreased. DAPI (4',6‑diamidino‑2‑phenylindole) and Annexin V/PI staining also revealed a significant increase in apoptotic bodies and apoptosis. Western blot analysis was performed to confirm the myricetin‑induced expression of apoptosis‑related proteins. The levels of cleaved PARP and Bax proteins were increased, and that of Bcl‑2 was decreased. The levels of proteins in the mitogen‑activated protein kinase (MAPK) pathway were examined to confirm the mechanism of myricetin‑induced apoptosis, and it was found that the expression levels of phosphorylated c‑Jun N‑terminal kinase (p‑JNK) and phosphorylated mitogen‑activated protein kinases (p‑p38) were increased, whereas that of phosphorylated extracellular‑regulated kinase (p‑ERK) was decreased. It was also demonstrated that myricetin induced autophagy by promoting autophagy‑related proteins such as microtubule‑associated protein 1A/1B‑light chain 3 (LC 3) and beclin 1. In addition, 3‑methyladenine (3‑MA) was used to evaluate the association between cell viability and autophagy in cells treated with myricetin. The results showed that simultaneous treatment with 3‑MA and myricetin promoted the apoptosis of breast cancer cells. Furthermore, treatment with a JNK inhibitor reduced cell viability, promoted Bax expression, and reduced the expression of p‑JNK, Bcl‑2, and LC 3‑II/I. These results suggest that myricetin induces apoptosis via the MAPK pathway and regulates JNK‑mediated autophagy in SK‑BR‑3 cells. In conclusion, myricetin shows potential as a natural anticancer agent in SK‑BR‑3 cells.

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