http://breast-cancer-research.com/content/12/4/R62
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
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.
The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.
Crit Rev Oncol Hematol. 2009 Dec 22. [Epub ahead of print]
Angioprevention with fenretinide: Targeting angiogenesis in prevention and therapeutic strategies.
Sogno I,
Venè R,
Ferrari N,
De Censi A,
Imperatori A,
Noonan DM,
Tosetti F,
Albini A.
IRCCS MultiMedica, Milano, Italy.
Abstract
Clinical trials have revealed that N-(4-hydroxyphenyl) retinamide (4HPR; fenretinide), a synthetic retinoic acid derivative, is a highly active and promising therapeutic and chemopreventive agent. Fenretinide shows biological activity against numerous cancer types in vitro and in preclinical studies. Clinical trials have shown that fenretinide induces a significant reduction of second breast cancer in premenopausal women. Several studies on different neoplasms are ongoing, such as breast and ovarian cancer, neuroblastoma, glioblastoma, head and neck and skin cancers and others. It has minimal side effects in humans, so that trials in young women at high-risk of breast cancer and ovarian and for the prevention of other tumor types such as lung cancer could be envisaged. Here we review some ongoing clinical trials and evaluate the possible mechanisms underlying the secondary chemopreventive effects of 4HPR. In particular we report basic and translational data on the anti-angiogenic "angiopreventive" properties of fenretinide, its anti-invasive activity, its ability to induce apoptosis and to generate or enhance production of reactive oxygen species as possible molecular bases for a chemopreventive action in patients. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.
PMID: 20034809 [PubMed - as supplied by publisher]