Kaempferol enhances cisplatin's effect on ovarian cancer cells through promoting apoptosis caused by down regulation of cMyc.
BACKGROUND
Ovarian cancer is one of the most significant malignancies in the western world. Studies showed that Ovarian cancers tend to grow resistance to cisplatin treatment. Therefore, new approaches are needed in ovarian cancer treatment. Kaempferol is a dietary flavonoid that is widely distributed in fruits and vegetables, and epidemiology studies have revealed a protective effect of kaempferol against ovarian cancer risk. Our early studies also found that kaempferol is effective in reducing vascular endothelial growth factor (VEGF) expression in ovarian cancer cells. In this study, we investigated kaempferol's effects on sensitizing ovarian cancer cell growth in response to cisplatin treatment.


RESULTS
Ten chemicals were screened for sensitizing OVCAR-3 ovarian cancer cell growth in response to cisplatin treatment. For kaempferol, which shows a significant synergistic interaction with cisplatin, expression of ABCC1, ABCC5, ABCC6, NFkB1, cMyc, and CDKN1A genes was further examined. For cisplatin/kaempferol treatments on OVCAR-3 cancer cells, the mRNA levels of ABCC1, ABCC5, and NFkB1 did not change. However, significant inhibition of ABCC6 and cMyc mRNA levels was observed for the cisplatin/kaempferol combined treatment. The CDKN1A mRNA levels were significantly up-regulated by cisplatin/kaempferol treatment. A plot of CDKN1A mRNA levels against that of cMyc gene further revealed a reverse, linear relationship, proving cMyc's regulation on CDKN1A gene expressions. Our work found that kaempferol works synergistically with cisplatin in inhibiting ovarian cancer cell viability, and their inhibition on cell viabilities was induced through inhibiting ABCC6 and cMyc gene transcription. Apoptosis assay showed the addition of 20 muM kaempferol to the cisplatin treatment induces the apoptosis of the cancer cells.


CONCLUSIONS
Kaempferol enhances the effect of cisplatin through down regulation of cMyc in promoting apoptosis of ovarian cancer cells. As a dietary component, kaempferol sensitizes ovarian cancer cells to cisplatin treatment and deserves further studies for possible applications in chemotherapy of ovarian cancers.
Luo
Haitao
H
Natural Science Division, Alderson-Broaddus College, Philippi, WV, 26416, USA. chenyc@ab.edu.
Daddysman
Matthew K
MK
Rankin
Gary O
GO
Jiang
Bing-Hua
BH
Chen
Yi C
YC
Am J Clin Nutr. 2007 Mar;85(3):895-909
17344514
Curr Med Chem. 2008;15(20):1981-2039
18691054
Clin Cancer Res. 2007 Mar 1;13(5):1611-9
17332308
Cancer Biol Ther. 2005 Sep;4(9):949-55
16082193
Nutr Cancer. 2008;60(6):800-9
19005980
Nature. 2002 Oct 17;419(6908):729-34
12384701
Clin Cancer Res. 2004 May 1;10(9):3169-78
15131058
CA Cancer J Clin. 2004 Jan-Feb;54(1):8-29
14974761
Semin Oncol. 1991 Jun;18(3):186-204
2042060
Cancer Epidemiol Biomarkers Prev. 2007 Apr;16(4):684-93
17416758
Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):15046-51
18818310
Arch Biochem Biophys. 2007 Apr 1;460(1):1-9
17353006
Br J Cancer. 2000 Jan;82(1):34-8
10638963
N Engl J Med. 1996 Jan 4;334(1):1-6
7494563
Cancer Epidemiol Biomarkers Prev. 2007 Jan;16(1):98-101
17220336
Nutr Cancer. 2006;56(2):225-31
17474869
Int J Cancer. 2007 Feb 15;120(4):906-17
17131310
Nutr Cancer. 2006;56(2):123-7
17474856
Mol Cancer Ther. 2007 Apr;6(4):1338-47
17431112