ANNURCA APPLE POLYPHENOL EXTRACT DECREASES THE IN VITRO MIGRATORY AND INVASIVE POTENTIAL OF TRIPLE NEGATIVE BREAST CANCER CELLS

Breast cancer is the most common invasive cancer among women in the world. Over the past two decades, although the treatment for breast cancer has substantially improved, its metastasis is still a major cause of mortality and poor prognosis. Cancer cell migration is essential for the early steps of metastasis, during which cancer cells move through the primary tumor and reach the blood vessels. Thus, suppression of cancer cell migration and invasion represents an important therapeutic target and the development of new therapeutic agents to prevent cancer cell migration and invasion is highly desirable. Triple-negative breast cancer (TNBC) is a highly invasive subgroup of breast carcinomas that lacks expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2. Proven active targeted therapy is presently unavailable for patients with TNBC and currently, chemotherapy represents the standard of care for patients with early advanced TNBC. Dietary polyphenols are among the naturally-occurring substances that have shown promising anti-cancer properties and low toxicity in comparison to standard chemotherapeutic agents. Previous works from our group led us to select polyphenol extract from Annurca apple (APE) as a potential candidate for drug development against breast cancer. We have indeed reported that APE displays a potent prooxidant cytotoxic effect in MCF-7 human breast carcinoma cells and, more recently, we demonstrated that APE is able to selectively kill MDA-MB-231 TNBC cells through ROS generation, sustained JNK activation and cell growth and survival inhibition while exerting a protective antioxidant effect in normal cells. The wound healing assay is widely used to investigate cell migrationin vitro and video-time lapse microscopy allows to monitor in real time the migration process. Several experimental factors, such as uneven cell density among different samples can affect the reproducibility and reliability of this assay. In this study the dose-dependent inhibitory effect exerted by APE on migration of MDAMB- 231 TNBC cells has been highlighted by means of a novel methodological approach to quantify wound healing process that is based on the analysis of the wound closure as a diffusion reaction process, and the potential underlying molecular mechanisms have been explored.