Delphinidin Inhibits HER2 and Erk1/2 Signaling and Suppresses Growth of HER2-Overexpressing and Triple Negative Breast Cancer Cell Lines.
Bottom Line: Delphinidin is a polyphenolic compound found in many brightly colored fruits and vegetables.MAPK signaling was partially reduced in triple negative cells and ER-negative chemically transformed MCF10A cells after treatment with delphinidin.In addition, delphinidin induced a significant level of apoptosis in HER2-overexpressing cells in association with reduced HER2 and MAPK signaling.
Affiliation: Departments of Pharmacology.
Delphinidin is a polyphenolic compound found in many brightly colored fruits and vegetables. Delphinidin is also the major bioactive component found in many dietary supplements that are currently consumed as complementary cancer medicine including pomegranate extract. The purpose of the current study was to determine the in vitro biological effects of delphinidin on established breast cancer cell lines of varying molecular subtypes in comparison to non-transformed breast epithelial cells. We examined cell proliferation, apoptosis, and growth inhibition in response to delphinidin using a tetrazolium salt-based assay, DNA fragmentation assay, and anchorage-independent growth assay. In comparison to vehicle control, delphinidin inhibited proliferation (P < 0.05), blocked anchorage-independent growth (P < 0.05), and induced apoptosis (P < 0.05) of ER-positive, triple negative, and HER2-overexpressing breast cancer cell lines with limited toxicity to non-transformed breast epithelial cells. MAPK signaling was partially reduced in triple negative cells and ER-negative chemically transformed MCF10A cells after treatment with delphinidin. In addition, delphinidin induced a significant level of apoptosis in HER2-overexpressing cells in association with reduced HER2 and MAPK signaling. Since delphinidin is often consumed as a complementary cancer medicine, the effect of delphinidin on response to specific HER2-targeted breast cancer therapies was examined by proliferation assay. Results of these drug combination studies suggested potential antagonism between delphinidin and HER2-directed treatments. In summary, the data presented here suggest that single agent delphinidin exhibits growth inhibitory activity in breast cancer cells of various molecular subtypes, but raise concerns regarding potential drug antagonism when used in combination with existing targeted therapies in HER2-overexpressing breast cancer.
No MeSH data available.
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Mentions: Anchorage-independent growth is considered to be an in vitro indicator of the invasive potential of cancer cells. Triple negative MDA231 and MDA468, and HER2-overexpressing SKBR3 and BT474 cells were plated in matrigel and treated with 50 μg/mL or 100 μg/mL of delphinidin for 3 to 4 weeks. All cell lines showed statistically significant reduction in anchorage-independent growth in response to delphinidin versus vehicle control and across all doses (Fig. 2A). Although delphinidin showed limited effects on proliferation and apoptosis of MDA468 cells, anchorage-independent growth was inhibited in this line as significantly as in other breast cancer lines, suggesting that delphinidin may inhibit invasiveness of breast cancer cells. In addition to anchorage-independent growth, cell migration in response to delphinidin was assessed. SKBR3 HER2-overexpressing breast cancer cells were plated as confluent cultures, and scratched down the middle to create an open area. Cells were then treated with DMSO control or 50 μg/mL delphinidin for 48 h (Fig. 2B). Delphinidin inhibited migration of SKBR3 cells. Collectively, these assays indicate that delphinidin blocks anchorage-independent growth and migration, suggesting that delphinidin may suppress the highly invasive potential of breast cancer cells of the triple negative or HER2-overexpressing molecular subtype.
No MeSH data available.