Sulforaphane suppresses the growth of EGFR‑overexpressing MDA‑MB‑468 triple‑negative breast cancer cells <em>in vivo</em> and <em>in vitro</em>

Yasunaga,Asuka; Ono,Misaki; Takeshima,Mikako; Nakano,Shuji

doi:10.3892/ijfn.2022.26

Sulforaphane suppresses the growth of EGFR‑overexpressing MDA‑MB‑468 triple‑negative breast cancer cells in vivo and in vitro

Authors:
- Asuka Yasunaga
- Misaki Ono
- Mikako Takeshima
- Shuji Nakano
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Affiliations: Graduate School of Health and Nutritional Sciences, Nakamura Gakuen University, Fukuoka 814‑0198, Japan
Published online on: March 23, 2022 https://doi.org/10.3892/ijfn.2022.26
Article Number: 3
Copyright: © Yasunaga et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Sulforaphane (SFN), found in cruciferous vegetables, has been found to exert potent antitumor effects against triple‑negative breast cancer (TNBC). The present study thus investigated the antitumor activity of SFN against MDA‑MB‑468 TNBC cells characterized by the overexpression of the epidermal growth factor receptor (EGFR) and the co‑deletion of the phosphatase and tensin homolog. SFN exerted concentration‑dependent anti‑proliferative effects, with a half‑maximal inhibitory concentration (IC₅₀) value of 1.8 µM following 72 h of exposure. SFN led to cell cycle arrest at the S phase and more predominantly, at the G2/M phase, and increased the sub‑G0/G1 cell population, which represented apoptotic cells, followed by the cleavage of poly(ADP‑ribose) polymerase. These data indicate that the inhibitory effects of SFN reflect the combination of S/G2/M cell cycle arrest and apoptotic cell death. SFN upregulated the expression of pro‑apoptotic B‑cell lymphoma (Bcl)‑2‑associated X (Bax) without affecting the expression of anti‑apoptotic Bcl‑2, suggesting that the increased expression of Bax plays a causative role in SFN‑induced apoptosis. SFN simultaneously inhibited the activities of protein kinase B (Akt) and mechanistic target of rapamycin (mTOR), thus indicating that SFN substantially inhibited the Akt/mTOR pathway, a survival signaling pathway downstream of the EGFR/phosphatidylinositol 3‑kinase. Furthermore, the oral administration of SFN significantly attenuated tumor growth in nude mice transplanted with MDA‑MB‑468 cells, without any apparent toxicity. On the whole, the findings of the present study suggest that SFN has therapeutic potential for use in the treatment of TNBC with an overactivated signaling pathway downstream of EGFR.

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