Investigation of the Potential Anticancer Effects of Lycopene in Tissue Engineered In vitro and In vivo Models

Abstract

Lycopene, primarily found in tomatoes and tomato-based products, is a phytochemical belonging to the group of carotenoids. Being an excellent antioxidant, it has proven to exert manyfold effects against chronic diseases, such as coronary heart disease or different types of cancer. Most studies investigating anti-cancer effects of lycopene have focused on prostate cancer so far. Within this context, it has been shown that the anti-cancer effects of lycopene are based on its anti-proliferative, anti-migrative, or anti-invasive properties, as well as on its potential to interfere in gap-junctional communication, to induce apoptosis and cell-cycle arrest, and to reduce oxidative DNA damage. The first step of this PhD work comprised the write up of an extensive literature review about lycopene´s molecular mechanisms and clinical effects on prostate cancer. This review summarizes in detail published in vitro, in vivo, and also clinical studies about lycopenes role in prostate cancer treatment and prevention. Based on these studies, it became clear that most of the in vitro and also in vivo data suggest a chemopreventive activity of lycopene against prostate cancer, but that the data is also in large parts inconcistent throughout the literature. In addition, there is still no clearly proven clinical evidence that supports therapeutic or preventive use of lycopene. Further literature search revealed that apart from prostate cancer, there is only few data concerning the usage of lycopene in the treatment and prevention of other cancer entities, such as ovarian cancer so far.For this reason, in order to harmize the data on prostate cancer and to extend the research into the direction of breast and ovarian cancer, we analysed the effects of lycopene in vitro on PC-3 and LNCaP prostate cancer cells, MDA-MB-231 breast cancer cells, and OV-MZ-6 and SKOV-3 ovarian cancer cells using both, a two-, as iii well as a three-dimensional tissue culture approach. These studies revealed significantly reduced cell viability upon treatment with lycopene at physiologically attainable concentrations throughout all cell lines on 2D monolayer cultures.However, there was no impact of lycopene on cell migration and invasion. A spheroid culture approach, using OV-MZ-6 and SKOV-3 ovarian cancer cells resulted in initially decreasing cell survival upon treatment with lycopene for 7 days, but increasing proliferation and viability after 14 days of exposure to the antioxidative compound, confirming the potential of lycopene to reduce cancer cell growth in short term cultures, but also indicating enhanced survival over prolonged exposure. Expanding on these rather heterogeneous results, we decided to perform an in vivo study to answer the question of lycopene´s antitumorigenic potential, as we assumed that the mixed outcome was primarily caused by dissolution problems of lycopene in cell culture. For this study, we used an intraperitoneal humanized animal model to test the preventive and therapeutic effects of lycopene alone or in combinatio...