Abstract 1607: Role of Obatoclax (GX15-070) and photodynami therapy, in vitro induction of apoptosis in breast cancer cells.
Authors: Coy-Arechavaleta Andrea Santos , Ramon-Allegos Eva , Martinez-Paniagua Melisa A. 
Published: August 2014

Breast cancer is the most common malignancy in women. Approximately one-third of women with breast cancer develop metastases and ultimately die of the disease. Breast epithelial cell homeostasis requires the balance of cell proliferation with a type of cell death called apoptosis. Changes in regulation of apoptosis may result in an increase in cell numbers. Apoptosis contributes to cell death in tumors treated with various anticancer agents. Chemo, surgery, radiation and hormone therapy are the conventional therapies, however some patients that initially respond to the therapy suffer recurrent disease or become resistant to the treatment. Chemoresistance often accompanies the progression of breast cancers from a hormone-dependent, non metastatic, antiestrogen-sensitive phenotype to a hormone independent, invasive, metastatic, antiestrogen resistan phenotype. For that reason it is important to identify novel therapies for breast cancer, recently photodynamic therapy (PDT) has been used to treat chest wall breast cancer recurrence. It induced cell death, manly through apoptosis, by oxidative stress. PDT was approved by United States FDA for the treatment of esophageal and lung cancer and actinic keratosis. The mechanism of action relies on a bimodal protocol in which visible light activates tumor cell-associated photosensitizer to produce reactive oxygen species. Mitochondrial damage has been suggested as an early event in PDT-mediated apoptosis, which could result in the release of apoptotic factors which activate the downstream targets in the apoptotic pathway. It has been suggested the protective role of the Bcl-2 family members in breast cancer tumors (Mcl 1 and Bcl-2). Obatoclax is a small molecule that mimics the BH3 domain of the BH3 only family members, inhibiting the effect of antiapoptotic Bcl-2 members. General purpose was to evaluate the pro-apoptotic effect of obatoclax in combination with photodynamic therapy (PDT) in vitro in breast cancer cells (MCF-7 and MDA-MB-231). Cell lines of breast cancer were cultured in the presence of delta amino-levulinic acid for 24 h. They were then irradiated to 30 or 60 J/cm2 in the presence or absence of obatoclax. Cell viability was measured using the colorimetric kit nonradioactive "XTT" (Roche, USA). Total extracts were obtained at the conditions described above to evaluate the expression of proteins by Western Blot. We evaluated the induction of apoptosis by TUNEL.

The viability of the cells treated with obatoclax or PDT alone was dose dependent. PDT-obatoclax combination treatments showed reduction of viability. Treatment with obatoclax showed variation in the expression of some proteins. Both treatments in breast cancer cells induced apoptosis.

Citation Format: Andrea Santos Coy-Arechavaleta, Eva Ramon-Allegos, Melisa A. Martinez-Paniagua. Role of Obatoclax (GX15-070) and photodynami therapy, in vitro induction of apoptosis in breast cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1607. doi:10.1158/1538-7445.AM2013-1607