See the published version of this preprint at Nutrition & Metabolism.
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Zhao He
Shandong University
Corresponding Author
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Background: Patients with estrogen receptor negative (ER-) breast cancer have poor prognosis due to high rates of metastasis. However, there is no effective treatment and drugs for ER- breast cancer metastasis. Our purpose of this study was to evaluate the effect of lotus leaf alcohol extract (LAE) on the cell migration and metastasis of ER- breast cancer.
Methods: The anti-migratory effect of LAE were analyzed in ER- breast cancer cells including SK-BR-3, MDA-MB-231 and HCC1806 cell lines. Cell viability assay, wound-healing assay, RNA-sequence analysis and immunoblotting assay were used to evaluate the cytotoxicity and anti-migratory effect of LAE. To further investigate the inhibitory effect of LAE on metastasis in vivo, subcutaneous xenograft and intravenous injection nude mice models were established. Lung and liver tissues were analyzed by the Hematoxylin & eosin staining and immunoblotting assay.
Results: We found that lotus leaf alcohol extract (LAE), not nuciferine, inhibited cell migration significantly in SK-BR-3, MDA-MB-231 and HCC1806 breast cancer cells, and did not affect viability of breast cancer cells. The anti-migratory effect of LAE was dependent on TGF-β1 signaling, while independent of Wnt signaling and autophagy influx. Intracellular H2O2 was involved in the TGF-β1-related inhibition of cell migration. LAE inhibited significantly the breast cancer cells metastasis in mice models. RNA-sequence analysis showed that extracellular matrix signaling pathways are associated with LAE-suppressed cell migration.
Conclusions: Our findings demonstrated that lotus leaf alcohol extract inhibits the cell migration and metastasis of ER- breast cancer, at least in part, via TGF-β1/Erk1/2 and TGF-β1/SMAD3 signaling pathways, which provides a potential therapeutic strategy for ER- breast cancer.
Keywords
Lotus leaf, cell migration, breast cancer, metastasis, TGF-β1 signaling pathway
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CURRENT STATUS: Published
View the published article at Nutrition & Metabolism.
Version 3
Posted 09 Jan, 2021
No community comments so far
Editorial decision: Accept
On 02 Feb, 2021
Reviewers invited
Invitations sent on 27 Dec, 2020
Editor assigned
On 25 Dec, 2020
Submission checks complete
On 25 Dec, 2020
Editor invited
On 25 Dec, 2020
No comments provided
Editorial decision: Minor revision
On 09 Dec, 2020
Review #1 received
Received 05 Dec, 2020
Reviewer #2 agreed
On 28 Oct, 2020
Reviewers invited
Invitations sent on 23 Oct, 2020
Reviewer #1 agreed
On 23 Oct, 2020
Editor assigned
On 21 Oct, 2020
Submission checks complete
On 20 Oct, 2020
Editor invited
On 20 Oct, 2020
No comments provided
Editorial decision: Major revision
On 20 Sep, 2020
Review #2 received
Received 18 Sep, 2020
Review #1 received
Received 01 Jun, 2020
Reviewers invited
Invitations sent on 18 May, 2020
Reviewer #1 agreed
On 18 May, 2020
Reviewer #2 agreed
On 18 May, 2020
Editor assigned
On 15 May, 2020
Editor invited
On 14 May, 2020
Submission checks complete
On 08 May, 2020
First submitted
On 01 May, 2020
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See the published version of this preprint at Nutrition & Metabolism.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Zhao He
Shandong University
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Nutrition & Metabolism.
Version 3
Posted 09 Jan, 2021
No community comments so far
Editorial decision: Accept
On 02 Feb, 2021
Reviewers invited
Invitations sent on 27 Dec, 2020
Editor assigned
On 25 Dec, 2020
Submission checks complete
On 25 Dec, 2020
Editor invited
On 25 Dec, 2020
No comments provided
Editorial decision: Minor revision
On 09 Dec, 2020
Review #1 received
Received 05 Dec, 2020
Reviewer #2 agreed
On 28 Oct, 2020
Reviewers invited
Invitations sent on 23 Oct, 2020
Reviewer #1 agreed
On 23 Oct, 2020
Editor assigned
On 21 Oct, 2020
Submission checks complete
On 20 Oct, 2020
Editor invited
On 20 Oct, 2020
No comments provided
Editorial decision: Major revision
On 20 Sep, 2020
Review #2 received
Received 18 Sep, 2020
Review #1 received
Received 01 Jun, 2020
Reviewers invited
Invitations sent on 18 May, 2020
Reviewer #1 agreed
On 18 May, 2020
Reviewer #2 agreed
On 18 May, 2020
Editor assigned
On 15 May, 2020
Editor invited
On 14 May, 2020
Submission checks complete
On 08 May, 2020
First submitted
On 01 May, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Nutrition & Metabolism.
Background: Patients with estrogen receptor negative (ER-) breast cancer have poor prognosis due to high rates of metastasis. However, there is no effective treatment and drugs for ER- breast cancer metastasis. Our purpose of this study was to evaluate the effect of lotus leaf alcohol extract (LAE) on the cell migration and metastasis of ER- breast cancer.
Methods: The anti-migratory effect of LAE were analyzed in ER- breast cancer cells including SK-BR-3, MDA-MB-231 and HCC1806 cell lines. Cell viability assay, wound-healing assay, RNA-sequence analysis and immunoblotting assay were used to evaluate the cytotoxicity and anti-migratory effect of LAE. To further investigate the inhibitory effect of LAE on metastasis in vivo, subcutaneous xenograft and intravenous injection nude mice models were established. Lung and liver tissues were analyzed by the Hematoxylin & eosin staining and immunoblotting assay.
Results: We found that lotus leaf alcohol extract (LAE), not nuciferine, inhibited cell migration significantly in SK-BR-3, MDA-MB-231 and HCC1806 breast cancer cells, and did not affect viability of breast cancer cells. The anti-migratory effect of LAE was dependent on TGF-β1 signaling, while independent of Wnt signaling and autophagy influx. Intracellular H2O2 was involved in the TGF-β1-related inhibition of cell migration. LAE inhibited significantly the breast cancer cells metastasis in mice models. RNA-sequence analysis showed that extracellular matrix signaling pathways are associated with LAE-suppressed cell migration.
Conclusions: Our findings demonstrated that lotus leaf alcohol extract inhibits the cell migration and metastasis of ER- breast cancer, at least in part, via TGF-β1/Erk1/2 and TGF-β1/SMAD3 signaling pathways, which provides a potential therapeutic strategy for ER- breast cancer.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
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