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vitamin A like compound synergistic w herceptin against her2+ER+ (and her2+er-) brst
cancer cells
Helped stem breast cancer growth, helped make the cells differentiate (stop acting like cancer cells and start behaving like normal breast cells with duties to perform) and the combination of herceptin and retinoid compounds caused apoptosis or cancer cell death.
Research article
Anti-tumor effects of retinoids combined with trastuzumab or tamoxifen in breast cancer cells: induction of apoptosis by retinoid/trastuzumab combinations
Debbie C Koay , Cynthia Zerillo , Murli Narayan , Lyndsay N Harris and Michael P DiGiovanna
Breast Cancer Research 2010, 12:R62doi:10.1186/bcr2625
Published: 9 August 2010
Abstract (provisional)
Introduction
HER2 and estrogen receptor (ER) are important in breast cancer and are therapeutic targets of trastuzumab (Herceptin) and tamoxifen, respectively. Retinoids inhibit breast cancer growth, and modulate signaling by HER2 and ER. We hypothesized that treatment with retinoids and simultaneous targeting of HER2 and/or ER may have enhanced anti-tumor effects.
Methods
The effects of retinoids combined with trastuzumab or tamoxifen were examined in two human breast cancer cell lines in culture, BT474 and SKBR3. Assays of proliferation, apoptosis, differentiation, cell cycle distribution, and receptor signaling were performed.
Results
In HER2-overexpressing/ER+ BT474 cells, combining all-trans retinoic acid (atRA) with tamoxifen or trastuzumab synergistically inhibited cell growth, and altered cell differentiation and cell cycle. Only atRA/trastuzumab-containing combinations induced apoptosis. BT-474 and HER2-overexpressing/ER- SKBR3 cells were treated with a panel of retinoids (atRA, 9-cis-retinoic acid (9-cis-RA), 13-cis-retinoic acid (13-cis-RA), or N-(4-hydroxyphenyl) retinamide (fenretinide) (4-HPR)) combined with trastuzumab. In BT-474 cells, none of the single agents except 4-HPR induced apoptosis, but again combinations of each retinoid with trastuzumab did induce apoptosis. In contrast, in SKBR3 cells, the single retinoid agents did cause apoptosis; this was only modestly enhanced by addition of trastuzumab. The retinoid drug combinations altered signaling by HER2 and ER. Retinoids were inactive in trastuzumab-resistant BT474 cells.
Conclusions
Combining retinoids with trastuzumab maximally inhibits cell growth and induces apoptosis in trastuzumab-sensitive cells. Treatment with such combinations may have benefit for breast cancer patients.
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