Silymarin inhibits proliferation of human breast cancer cells via regulation of the MAPK signaling pathway and induction of apoptosis

Kim,Sung-Hyun; Choo,Gang-Sik; Yoo,Eun-Seon; Woo,Joong-Seok; Lee,Jae-Han; Han,So-Hee; Jung,Soo-Hyun; Kim,Hyeong-Jin; Jung,Ji-Youn

doi:10.3892/ol.2021.12753

Silymarin inhibits proliferation of human breast cancer cells via regulation of the MAPK signaling pathway and induction of apoptosis

Authors:
- Sung-Hyun Kim
- Gang-Sik Choo
- Eun-Seon Yoo
- Joong-Seok Woo
- Jae-Han Lee
- So-Hee Han
- Soo-Hyun Jung
- Hyeong-Jin Kim
- Ji-Youn Jung
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Affiliations: Department of Companion and Laboratory Animal Science, Kongju National University, Yesan, Chungcheongnam 340-702, Republic of Korea
Published online on: April 26, 2021 https://doi.org/10.3892/ol.2021.12753
Article Number: 492
Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Silymarin is a purified mixture of four isomeric flavonoids extracted from the seeds and fruit of the milk thistle plant, Silybum marianus (L.). Silymarin exhibits a wide variety of biological effects and is commonly used in traditional medicine. Therefore, the anticancer effects of silymarin on human breast cancer cells were investigated to determine its pharmacological mechanisms in vitro and in vivo. The viability and proliferation of MDA‑MB‑ 231 and MCF‑7 breast cancer cells were investigated using MTT and wound healing assays. Silymarin decreased the viability and proliferation of MDA‑MB‑231 and MCF‑7 cells in a concentration‑dependent manner. The number of apoptotic bodies, as shown by DAPI staining, was increased in a concentration‑dependent manner, indicating that silymarin induces apoptosis. Additionally, changes in the expression levels of apoptosis‑related proteins were demonstrated in human breast cancer cells using western blotting. Silymarin increased the levels of Bax, cleaved poly‑ADP ribose polymerase, cleaved caspase‑9 and phosphorylated (p‑)JNK, and decreased the levels of Bcl‑2, p‑P38 and p‑ERK1/2. Furthermore, the inhibitory effects of silymarin on MCF‑7 tumor growth were investigated. In mice treated with silymarin for 3 weeks (25 and 50 mg/kg), MCF‑7 tumor growth was inhibited without organ toxicity. In MCF‑7 tumors, silymarin induced apoptosis and decreased p‑ERK1/2 levels, as assessed using a TUNEL assay and immunohistochemistry. These results indicated that silymarin inhibited breast cancer cell proliferation both in vitro and in vivo by modulating the MAPK signaling pathway. Therefore, silymarin may potentially be used as a chemo‑preventive or therapeutic agent.

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