2. Academic Validation
  3. Eriocalyxin B, a novel autophagy inducer, exerts anti-tumor activity through the suppression of Akt/mTOR/p70S6K signaling pathway in breast cancer

Eriocalyxin B, a novel autophagy inducer, exerts anti-tumor activity through the suppression of Akt/mTOR/p70S6K signaling pathway in breast cancer

  • Biochem Pharmacol. 2017 Oct 15:142:58-70. doi: 10.1016/j.bcp.2017.06.133.
Xunian Zhou 1,  Grace Gar-Lee Yue 2,  Andrew Man-Lok Chan 3,  Stephen Kwok-Wing Tsui 3,  Kwok-Pui Fung 4,  Handong Sun 5,  Jianxin Pu 6,  Clara Bik-San Lau 7
Affiliations

Affiliations

  • 1 School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China; Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
  • 2 Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
  • 3 School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
  • 4 School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China; Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
  • 5 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, China.
  • 6 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, China. Electronic address: pujianxin@mail.kib.ac.cn.
  • 7 Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China. Electronic address: claralau@cuhk.edu.hk.
PMID: 28669564 DOI: 10.1016/j.bcp.2017.06.133
Abstract

Eriocalyxin B (EriB), a natural ent-kaurane diterpenoid presented in the plant Isodon eriocalyx var. laxiflora, has been reported to diminish angiogenesis-dependent breast tumor growth. In the present study, the effects of EriB on human breast Cancer and its underlying mechanisms were further investigated. The in vitro anti-breast Cancer activity of EriB was determined using MCF-7 and MDA-MB-231 cell lines. MDA-MB-231 xenograft model of human breast Cancer was also established to explore the anti-tumor effect in vivo. We found that EriB was able to induce Apoptosis accompanied by the activation of Autophagy, which was evidenced by the increased accumulation of autophagosomes, acidic vesicular organelles formation, the microtubule-associated protein 1A/1B-light chain 3B-II (LC3B-II) conversion from LC3B-I and p62 degradation. Meanwhile, EriB treatment time-dependently decreased the phosphorylation of Akt, mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase (p70S6K), leading to the inhibition of Akt/mTOR/p70S6K signaling pathway. Moreover, the blockage of Autophagy obviously sensitized EriB-induced cell death, which suggested the cytoprotective function of Autophagy in both MCF-7 and MDA-MB-231 cells. Interestingly, the autophagic features and Apoptosis induction were prevented by Reactive Oxygen Species (ROS) scavenger N-acetyl-l-cysteine, indicating that ROS played an essential role in the mediation of EriB-induced cell death. Furthermore, in MDA-MB-231 xenograft model, EriB displayed a significant anti-tumor effect via the activation of Autophagy and Apoptosis in breast tumor cells. Taken together, our findings firstly demonstrated that EriB suppressed breast Cancer cells growth both in vitro and in vivo, and thus could be developed as a promising anti-breast tumor agent.

Keywords

3-Methyladenine (Pubchem CID: 1673); Apoptosis; Autophagy; Breast cancer; Chloroquine (Pubchem CID); Eriocalyxin B; Eriocalyxin B (Pubchem CID: 367620); Reactive oxygen species; mTOR.

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