Version 1
: Received: 22 January 2017 / Approved: 23 January 2017 / Online: 23 January 2017 (03:30:01 CET)
How to cite:
Jandial, D.D.; Krill, L.S.; Chen, L.; Wu, C.; Ke, Y.; Xie, J.; Hoang, B.H.; Zi, X. Induction of G2M Arrest by Flavokawain A, A Kava Chalcone, Increases the Responsiveness of HER2 Overexpressing Breast Cancer Cells to Herceptin. Preprints2017, 2017010098. https://doi.org/10.20944/preprints201701.0098.v1
Jandial, D.D.; Krill, L.S.; Chen, L.; Wu, C.; Ke, Y.; Xie, J.; Hoang, B.H.; Zi, X. Induction of G2M Arrest by Flavokawain A, A Kava Chalcone, Increases the Responsiveness of HER2 Overexpressing Breast Cancer Cells to Herceptin. Preprints 2017, 2017010098. https://doi.org/10.20944/preprints201701.0098.v1
Jandial, D.D.; Krill, L.S.; Chen, L.; Wu, C.; Ke, Y.; Xie, J.; Hoang, B.H.; Zi, X. Induction of G2M Arrest by Flavokawain A, A Kava Chalcone, Increases the Responsiveness of HER2 Overexpressing Breast Cancer Cells to Herceptin. Preprints2017, 2017010098. https://doi.org/10.20944/preprints201701.0098.v1
APA Style
Jandial, D.D., Krill, L.S., Chen, L., Wu, C., Ke, Y., Xie, J., Hoang, B.H., & Zi, X. (2017). Induction of G2M Arrest by Flavokawain A, A Kava Chalcone, Increases the Responsiveness of HER2 Overexpressing Breast Cancer Cells to Herceptin. Preprints. https://doi.org/10.20944/preprints201701.0098.v1
Chicago/Turabian Style
Jandial, D.D., Bang H. Hoang and Xiaolin Zi. 2017 "Induction of G2M Arrest by Flavokawain A, A Kava Chalcone, Increases the Responsiveness of HER2 Overexpressing Breast Cancer Cells to Herceptin" Preprints. https://doi.org/10.20944/preprints201701.0098.v1
Abstract
HER2/neu positive breast tumors predict a high mortality and comprise 25-30% of breast cancer. We have shown that Flavokawain A (FKA) preferentially reduces the viabilities of HER2 overexpressing breast cancer cell lines (i.e. SKBR3 and MCF7/HER2) versus those with less HER2 expression (i.e. MCF7 and MDA-MB-468). FKA at cytotoxic concentrations to breast cancer cell lines also has minimal effect on the growth of non-malignant breast epithelial MCF10 cells. FKA induces G2M arrest in cell cycle progression of HER2 overexpressing breast cancer cell lines through inhibition of Cdc2 and Cdc25C phosphorylation and down-regulation of Myt1 and Wee1expression leading to increased Cdc2 kinase activities. In addition, FKA induces apoptosis in SKBR3 cells by increasing the protein expression of Bim and BAX and decreasing expression of Bcl2, Bclx/L , XIAP and survivin. FKA also down-regulates the protein expression of HER-2 and inhibits AKT phosphorylation. Herceptin plus FKA treatment leads to enhanced growth inhibitory effect on HER-2 overexpressing breast cancer cell lines through down-regulation of Myt1, Wee1, Skp2, Survivin and XIAP. Our results suggest the promise of FKA as a novel apoptosis inducer and G2 checkpoint abrogating agent in combination with Herceptin for treatment of HER2 overexpressing breast cancer.
Keywords
Flavokawain A; HER2 overexpression; resistance to apoptosis
Subject
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
