Supervisors: dr hab. Anna Ptak, prof. UJ (anna.ptak@uj.edu.pl)

Institute of Zoology and Biomedical Research

Background information:

Despite continued efforts and steady improvements in treatment over the past decades, ovarian cancer remains the deadliest malignancy in women. Worldwide, there are 313,959 new cases (1.6% of all cancers) and 207,252 deaths (2.1% of all cancer deaths) each year (Globocan 2020). This means that more than 66% of patients die from the disease. Recently, natural product therapy has received increased attention in an effort to improve the therapeutic index of certain antineoplastic drugs. Importantly, evidence suggests that dysregulated metabolism in cancer cells is more than a hallmark of cancer, but may be the underlying cause of the tumor [1]. We believe that in this context the bioactive compounds of sheep's milk may have an effective outcome and should be carefully considered. Sheep's milk has health-promoting properties, mainly due to the presence of bioactive and antioxidant substances that have a positive effect on metabolic processes. Sheep's milk is an important natural source of conjugated linoleic acid (CLA) and orotic acid (OA). Some studies have shown that c9,t11 CLA isomers reduce breast cancer progression in vivo by affecting hormone receptor levels and cell proliferation, while our pilot studies have shown that OA at a lower dose than sheep's milk can selectively reduce the viability of ovarian granulosa tumor cells by inducing caspase-3 activity, without negative effects on non-cancerous granulosa cells [2].

The main question to be addressed in the project:

The main aim of the project is to test whether bioactive constituents of sheep's milk, such as CLA and OA, which act via metabolic pathway regulation, can be used as a powerful weapon to support standard ovarian cancer therapy.

Information on the methods/description of work:

Our proposed research will use three experimental systems to define the universal mechanism of action of the components of sheep's milk: human ovarian cell lines grown in vitro, mice with experimentally induced human ovarian cancer (in vivo) and ovarian cancer organoids derived from patient biopsies.

Additional information (e.g Special requirements from the student):

- experience in cell culture, molecular biology techniques like ELISA, fluorometric and/or colorimetric analysis, and proteomic analysis; - completed courses on Tissue Culture and Hormonally Active Compounds in the Environment.

References:

[1] Gyamfi J, Kim J, Choi J. Cancer as a Metabolic Disorder. Int J Mol Sci. 2022 Jan 21;23(3):1155. doi: 10.3390/ijms23031155.

[2] Marynowicz W, Borski N, Flis Z, Ptak A, Molik E. Orotic acid induces apoptotic death in ovarian adult granulosa tumour cells and increases mitochondrial activity in normal ovarian granulosa cells. Reprod Biol. 2023 Sep;23(3):100790. doi: 10.1016/j.repbio.2023.100790.