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Combinational Effects of Polymethoxyflavones and Atorvastatin in Inhibiting Human Breast Cancer Cells

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dc.contributor.advisorHang Xiao
dc.contributor.authorLi, Longfang
dc.contributor.departmentUniversity of Massachusetts Amherst
dc.contributor.departmentFood Science
dc.date2023-09-23T07:36:02.000
dc.date.accessioned2024-04-26T20:34:46Z
dc.date.available2012-11-27T00:00:00Z
dc.date.issued2013-01-01
dc.date.submittedFebruary
dc.description.abstractUtilization of potential synergistic interactions among different bioactive agents is a promising approach to inhibit complex diseases such as cancer. Nobiletin (NBT) and tangeretin (TAN) are major polymethoxyflavones (PMFs) found in citrus fruits. Herein, we studied NBT and TAN in combination with atorvastatin (ATST, Lipitor, a cholesterol-lowering drug) in MDAMB231 and MCF-7 human breast cancer cells. Both NBT/ATST and TAN/ATST combinations at low doses produced much stronger inhibitory effect on cancer cell viability in comparison to those produced by NBT, TAN, or ATST alone at much higher doses. Isobologram analysis confirmed that both NBT/ATST and TAN/ATST combinations produced strong synergy in inhibiting the growth of two breast cancer cell lines. Flow cytometry analysis showed that both NBT/ATST and TAN/ATST combinations caused significant cell cycle arrest at G0/G1 phase in MDAMB231 cells (ER+). Consistent with these results, PMFs and ATST combinations decreased expression levels of phospho Rb, cyclin D1, and CDK4. Further experiments showed that the combination treatment induced autophagy and late apoptosis in MDA-MB-231 cells. Meanwhile, co-treatment of PMFs and ATST induce G2/M phase in MCF-7 (ER+) cells.. The combination of PMFs and ATST also caused autophagy in MCF-7 cells, which was evidenced by activation of LC3B and P62. In conclusion, our result demonstrated strong synergy between two major citrus PMFs (NBT and TAN) and ATST in inhibiting human breast cancer cell growth.
dc.description.degreeMaster of Science (M.S.)
dc.identifier.doihttps://doi.org/10.7275/3493924
dc.identifier.urihttps://hdl.handle.net/20.500.14394/44430
dc.relation.urlhttps://scholarworks.umass.edu/cgi/viewcontent.cgi?article=2102&context=theses&unstamped=1
dc.source.statuspublished
dc.subject: Polymethoxyflavones; Atorvastatin; Combination; Synergy effect; Autophagy; Apoptosis; Human Breast cancer cells MCF-7 (ER+)
dc.subjectMDA-MB-231 (ER-)
dc.subjectFood Science
dc.titleCombinational Effects of Polymethoxyflavones and Atorvastatin in Inhibiting Human Breast Cancer Cells
dc.typecampus
dc.typearticle
dc.typethesis
digcom.contributor.authorisAuthorOfPublication|email:qqlonger@hotmail.com|institution:University of Massachusetts Amherst|Li, Longfang
digcom.date.embargo2012-11-27T00:00:00-08:00
digcom.identifiertheses/1005
digcom.identifier.contextkey3493924
digcom.identifier.submissionpaththeses/1005
dspace.entity.typePublication
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