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

TitleEriocalyxin B, a novel autophagy inducer, exerts anti-tumor activity through the suppression of Akt/mTOR/p70S6K signaling pathway in breast cancer
Authors
KeywordsApoptosis
Autophagy
Breast cancer
Eriocalyxin B
mTOR
Reactive oxygen species
Issue Date2017
Citation
Biochemical Pharmacology, 2017, v. 142, p. 58-70 How to Cite?
AbstractEriocalyxin 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.
Persistent Identifierhttp://hdl.handle.net/10722/343241
ISSN
2023 Impact Factor: 5.3
2023 SCImago Journal Rankings: 1.365

 

DC FieldValueLanguage
dc.contributor.authorZhou, Xunian-
dc.contributor.authorYue, Grace Gar Lee-
dc.contributor.authorChan, Andrew Man Lok-
dc.contributor.authorTsui, Stephen Kwok Wing-
dc.contributor.authorFung, Kwok Pui-
dc.contributor.authorSun, Handong-
dc.contributor.authorPu, Jianxin-
dc.contributor.authorLau, Clara Bik San-
dc.date.accessioned2024-05-10T09:06:33Z-
dc.date.available2024-05-10T09:06:33Z-
dc.date.issued2017-
dc.identifier.citationBiochemical Pharmacology, 2017, v. 142, p. 58-70-
dc.identifier.issn0006-2952-
dc.identifier.urihttp://hdl.handle.net/10722/343241-
dc.description.abstractEriocalyxin 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.-
dc.languageeng-
dc.relation.ispartofBiochemical Pharmacology-
dc.subjectApoptosis-
dc.subjectAutophagy-
dc.subjectBreast cancer-
dc.subjectEriocalyxin B-
dc.subjectmTOR-
dc.subjectReactive oxygen species-
dc.titleEriocalyxin B, a novel autophagy inducer, exerts anti-tumor activity through the suppression of Akt/mTOR/p70S6K signaling pathway in breast cancer-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.bcp.2017.06.133-
dc.identifier.pmid28669564-
dc.identifier.scopuseid_2-s2.0-85021856637-
dc.identifier.volume142-
dc.identifier.spage58-
dc.identifier.epage70-
dc.identifier.eissn1873-2968-

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