Home Food Science and Human Wellness Article
PDF (5.2 MB)
Cite
EndNote(RIS) BibTeX
Collect
Submit Manuscript
Open Access

High β-sitosterol-D-glucoside content in sweet potato varieties and its anti-breast cancer potential through multiple metastasis-associated signals

Jinyin Zhanga, Lu Huangb, Xiang Tangb, Miao Pana, Xiaoli Yeb, Xuegang Lia(), Hang Maa()
School of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China
School of Life Sciences, Southwest University, Chongqing 400715, China

Peer review under responsibility of Tsinghua University Press.

Show Author Information

Highlights

• A high β-sitosterol-D-glucoside sweet potato variety was selected from 36 common varieties.

• Proteomic analysis found that β-sitosterol-D-glucoside suppresses breast cancer metastasis by inhibiting epithelial-mesenchymal transition.

• Multiple metastasis-associated proteins, including N-cadherin, VIM, Snails, VEGF, MMP2, MMP9, PPP2CA, SNX9, and HMGB3, are involved in the anti-metastasis effect of β-sitosterol-D-glucoside.

Abstract

β-Sitosterol-D-glucoside (β-SDG) is a phytosterol compound whose antitumor activity has been confirmed by previous studies. However, its suppression on breast cancer remains unclear. To that purpose, we isolated β-SDG from sweet potato and investigated the breast-cancer-inhibiting mechanism using proteomic analysis. The sweet potato species S6 with high β-SDG content were chosen form 36 species and β-SDG was isolated by HPLC. Afterwards, an in situ animal model of breast cancer was established, and β-SDG significantly reduced the tumor volume of MCF-7 xenograft mice. Proteomic analysis of tumor tissues revealed that 127 of these proteins were upregulated and 80 were downregulated. Gene ontology and network analysis showed that regulatory proteins were mainly associated with epithelial-mesenchymal transition (EMT), myogenesis, cholesterol homeostasis, oxidative phosphorylation and reactive oxygen pathways, while Vimentin, NDUF, VDAC1, PPP2CA and SNx9 were the most significant 5 node degree genes. Meanwhile, in vitro and in vivo results showed that the protein expression of PPP2CA and Vimentin, which are markers of EMT, were involved in breast cancer cell metastasis and could be reversed by β-SDG. This work highlights β-SDG as a bioactive compound in sweet potato and the potential therapeutic effect of β-SDG for the treatment of breast cancer by inhibiting metastasis.

Keywords

β-Sitosterol-D-glucoside (β-SDG)Sweet potatoBreast cancerProteomicMetastasis

References

[1]

H. Sung, J. Ferlay, R. Siegel, et al., Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries, CA A Cancer J. Clin. 71(3) (2021) 209-249. https://doi.org/10.3322/caac.21660.

Crossref Google Scholar
[2]

R. Sen, N. Bhutani, J. Kamboj, et al., Primary acinic cell carcinoma of the breast: a case report with a clinicopathological and immunohistochemical study of a rare breast cancer subtype, Ann. Med. Surg. 35 (2018) 137-140. https://doi.org/10.1016/j.amsu.2018.09.030.

Crossref Google Scholar
[3]

N. Conlon, J. Howard, J. Catalano, et al., Breast carcinoma in young women: no evidence of increasing rates of metastatic breast carcinoma in a single tertiary center review, Breast J. 22(3) (2016) 287-292. https://doi.org/10.1111/tbj.12575.

Crossref Google Scholar
[4]

B.J. van Denderen, E.W. Thompson, Cancer: the to and fro of tumour spread, Nature 493 (2013) 487-488. https://doi.org/10.1038/493487a.

Crossref Google Scholar
[5]

K.H. Lau, A.M. Tan, Y. Shi, New and emerging targeted therapies for advanced breast cancer, IJMS 23(4) (2022) 2288. https://doi.org/10.3390/ijms23042288.

Crossref Google Scholar
[6]

M. Park, D. Kim, S. Ko, et al., Breast cancer metastasis: mechanisms and therapeutic implications, IJMS 23(12) (2022) 6806. https://doi.org/10.3390/ijms23126806.

Crossref Google Scholar
[7]

K.R. Fischer, A. Durrans, S. Lee, et al., Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance, Nature 527 (2015) 472-476. https://doi.org/10.1038/nature15748.

Crossref Google Scholar
[8]

A.M. Richardson, L.S. Havel, A.E. Koyen, et al., Vimentin is required for lung adenocarcinoma metastasis via heterotypic tumor cell-cancer-associated fibroblast interactions during collective invasion, Clin. Cancer Res. 24(2) (2018) 420-432. https://doi.org/10.1158/1078-0432.CCR-17-1776.

Crossref Google Scholar
[9]

W. Wang, L. Wang, A. Mizokami, et al., Down-regulation of E-cadherin enhances prostate cancer chemoresistance via notch signaling, Chin. J. Cancer 36(1) (2017) 35. https://doi.org/10.1186/s40880-017-0203-x.

Crossref Google Scholar
[10]

Y.S. Baraya, K.K. Wong, N.S. Yaacob, Strobilanthes crispus inhibits migration, invasion and metastasis in breast cancer, J. Ethnopharmacol. 233 (2019) 13-21. https://doi.org/10.1016/j.jep.2018.12.041.

Crossref Google Scholar
[11]

N. Song, B. Liu, J.L. Wu, et al., Prognostic value of HMGB3 expression in patients with non-small cell lung cancer, Tumour Biol. 34(5) (2013) 2599-2603. https://doi.org/10.1007/s13277-013-0807-y.

Crossref Google Scholar
[12]

H.R. Tang, X.Q. Luo, G. Xu, et al., High mobility group-box 3 overexpression is ssociated waith poor prognosis of resected gastric adenocarcinoma, World J. Gastroenterol. 18(48) (2012) 7319-7326. https://doi.org/10.3748/wjg.v18.i48.7319.

Crossref Google Scholar
[13]

M.K. Alam, A comprehensive review of sweet potato (Ipomoea Batatas[L.] Lam): revisiting the associated health benefits, Trends Food Sci. Tech. 115 (2021) 512-529. https://doi.org/10.1016/j.tifs.2021.07.001.

Crossref Google Scholar
[14]

Z.C. Zhang, G.H. Su, C.L. Luo, et al., Effects of nathocyanins from purple sweet potato (Ipomoea Batatas L. Cultivar Eshu No. 8) on the serum uric acid level and xanthine oxidase activity in hyperuricemic mice, Food Funct. 6(9) (2015) 3045-3055. https://doi.org/10.1039/C5FO00499C.

Crossref Google Scholar
[15]

H.H. Jang, H.W. Kim, S.Y. Kim, et al., In vitro and in vivo hypoglycemic effects of cyanidin 3-caffeoyl-p-hydroxybenzoylsophoroside-5-glucoside, an anthocyanin isolated from purple-fleshed sweet potato, Food Chem. 272 (2019) 688-693. https://doi.org/10.1016/j.foodchem.2018.08.010.

Crossref Google Scholar
[16]

Q.Wu, H. Qu, J. Jia, et al., Characterization, antioxidant and antitumor activities of polysaccharides from purple sweet potato, Carbohydrate Polym. 132 (2015) 31-40. https://doi.org/10.1016/j.carbpol.2015.06.045.

Crossref Google Scholar
[17]

M. Wang, H. Ma, C. Tian, et al., Bioassay-guided isolation of glycoprotein SPG-56 from sweet potato zhongshu-1 and its anti-colon cancer activity in vitro and in vivo, J. Funct. Foods 35 (2017) 315-324. https://doi.org/10.1016/j.jff.2017.05.049.

Crossref Google Scholar
[18]

M.A. Esmaeili, M.M. Farimani, Inactivation of PI3K/Akt pathway and upregulation of PTEN gene are involved in daucosterol, isolated from salvia sahendica, induced apoptosis in human breast adenocarcinoma cells, S. Afr. J. Bot. 93 (2014) 37-47. https://doi.org/10.1016/j.sajb.2014.03.010.

Crossref Google Scholar
[19]

P. Jiang, B. Han, L. Jiang, et al., Simultaneous separation and quantitation of three phytosterols from the sweet potato, and determination of their anti-breast cancer activity, J. Pharm. Biome. Anal. 174 (2019) 718-727. https://doi.org/10.1016/j.jpba.2019.06.048.

Crossref Google Scholar
[20]

H. Xu, Y. Li, B. Han, et al., Anti-breast-cancer activity exerted by β-sitosterol-D-glucoside from sweet potato via upregulation of microRNA-10a and via the PI3K-Akt signaling pathway, Food Chem. 66(37) (2018) 9704-9718. https://doi.org/10.1021/acs.jafc.8b03305.

Crossref Google Scholar
[21]

G. Babaei, S.G.G. Aziz, N.Z.Z. Jaghi, EMT, cancer stem cells and autophagy, the three main axes of metastasis, Biomed. Pharmacother. 133 (2021) 110909. https://doi.org/10.1016/j.biopha.2020.110909.

Crossref Google Scholar
[22]

FAOSTAT. Statistics division of food and agriculture Organization of the United Nations. (2020).

[23]

F. Bray, J. Ferlay, I. Soerjomataram, et al., Erratum: global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries, CA A Cancer J. Clin. 70(4) (2020) 313-313. https://doi.org/10.3322/caac.21609.

Crossref Google Scholar
[24]

C. Zhao, T. She, L. Wang, et al., Daucosterol inhibits cancer cell proliferation by inducing autophagy through reactive oxygen species-dependent manner, Life Sci. 137 (2015) 37-43. https://doi.org/10.1016/j.lfs.2015.07.019.

Crossref Google Scholar
[25]

A. Bhardwaj, S. Singh, S.K. Srivastava, et al., Restoration of PPP2CA expression reverses epithelial-to-mesenchymal transition and suppresses prostate tumour growth and metastasis in an orthotopic mouse model, Br. J. Cancer 110(8) (2014) 141. https://doi.org/10.1038/bjc.2014.141.

Crossref Google Scholar
[26]

Z. Zhang, Y. Chang, J. Zhang, et al., HMGB3 promotes growth and migration in colorectal cancer by regulating WNT/β-catenin pathway, PLoS ONE 12(7) (2017) e0179741. https://doi.org/10.1371/journal.pone.0179741.

Crossref Google Scholar
[27]

M. Li, Y. Cai, H. Zhao, et al., Overexpression of HMGB3 protein promotes cell proliferation, migration and is associated with poor prognosis in urinary bladder cancer patients, Tumor Biol. 36(6) (2015) 4785-4792. https://doi.org/10.1007/s13277-015-3130-y.

Crossref Google Scholar
[28]

Y. Lü, M. Lü, X. Ji, et al., Down-regulated expressed protein HMGB3 inhibits proliferation and migration, promotes apoptosis in the placentas of fetal growth restriction, Int. J. Biochem. Cell Biol. 107 (2019) 69-76. https://doi.org/10.1016/j.biocel.2018.11.007.

Crossref Google Scholar
[29]

N. Bendris, S.L. Schmid, Endocytosis, metastasis and beyond: multiple facets of SNX9, Trends Cell Biol. 27(3) (2017) 189-200. https://doi.org/10.1016/j.tcb.2016.11.001.

Crossref Google Scholar
[30]

A. Satelli, S. Li, Vimentin in cancer and its potential as a molecular target for cancer therapy, Cell. Mol. Life Sci. 68(18) (2011) 3033-3046. https://doi.org/10.1007/s00018-011-0735-1.

Crossref Google Scholar
[31]

J.P. Thiery, H. Acloque, R.Y.J. Huang, et al., Epithelial-mesenchymal transitions in development and disease, Cell 139(5) (2009) 871-890. https://doi.org/10.1016/j.cell.2009.11.007.

Crossref Google Scholar
[32]

F. Lüönd, N. Sugiyama, R. Bill, et al., Distinct contributions of partial and full EMT to breast cancer malignancy, Dev. Cell 56(23) (2021) 3203-3221. https://doi.org/10.1016/j.devcel.2021.11.006.

Crossref Google Scholar
[33]

Z. Yang, D. Wu, Y. Chen, et al., GRHL2 inhibits colorectal cancer progression and metastasis via oppressing epithelial-mesenchymal transition, Cancer Biol. Ther. 20(9) (2019) 1195-1205. https://doi.org/10.1080/15384047. 2019.1599664.

Crossref Google Scholar
Food Science and Human Wellness
Volume 13 Issue 5,
September 2024
Pages 2779-2789
DOI: 10.26599/FSHW.2022.9250225
Cite this article:
Zhang J, Huang L, Tang X, et al. High β-sitosterol-D-glucoside content in sweet potato varieties and its anti-breast cancer potential through multiple metastasis-associated signals. Food Science and Human Wellness, 2024, 13(5): 2779-2789. https://doi.org/10.26599/FSHW.2022.9250225
Metrics & Citations  
Article History
Copyright
Rights and Permissions
Return