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Polymethoxyflavones and Atorvastatin Synergistically Inhibits Breast Cancer Cell Growth
Author(s) -
li longfang,
Charoensinphon Noppawat,
Zheng Jinkai,
Xiao Hang
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.644.18
Subject(s) - atorvastatin , nobiletin , breast cancer , cancer , chemistry , cancer research , cell growth , mcf 7 , pharmacology , biology , human breast , medicine , biochemistry , flavonoid , antioxidant
Utilization 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 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 G 0 /G 1 phase in both MDAMB231 and MCF‐7 cells after 48 hrs of treatments. Consistent with these results, NBT/ATST and TAN/ATST combinations decreased expression levels of Akt, cyclin D1, and CDK4, while increased expression levels of p21, PTEN, and phosphorylated PTEN (Ser380). In conclusion, our result demonstrated strong synergy between two major citrus polymethoxyflavones and ATST in inhibiting human breast cancer cell growth. Grant Funding Source : NIH:CA139174, AICR:#10A044