Dissertation committee:
Θεόδωρος Τρουπής, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Βασίλειος Πρωτογέρου Αναπληρωτής Καθηγητής Ανατομίας, Ιατρική Σχολή, ΕΚΠΑ
Αντώνιος Μαζαρακης Αναπληρωτής Καθηγητής Ανατομίας, Ιατρική Σχολή, ΕΚΠΑ
Μάρα Πιαγκου. Επίκουρη Καθηγήτρια Ανατομίας, Ιατρική Σχολή, ΕΚΠΑ
Αναστάσης Στεφάνου, Καθηγητής, Ιατρική Σχολή, Ευρωπαϊκό Πανεπιστήμιο Κύπρου
Ιωάννης Πατρίκιος, Καθηγητής, Ιατρική Σχολή, Ευρωπαϊκό Πανεπιστήμιο Κύπρου
Ελισάβετ Τζόνσον, Καθηγήτρια Ανατομίας, Ιατρική Σχολή, Ευρωπαϊκό Πανεπιστήμιο Κύπρου, Επιβλέπουσα
Summary:
Cancer is a leading cause of death and mortality in the world and by 2030 the numbers of new cancer cases is expected to rise 23.6 million. Although conventional chemotherapy is still the first choice of treatment, such procedures is associated with major cytotoxic side effects. In the present study it was shown that the phyto-compound annonacin (found in the fruit Graviola / Annona muricata) promotes anti-cancer activity in cancer cell lines. In contrast, annoancin showed limited toxicity in normal and non-transformed cells. In order to identify the cellular and molecular target of annonacin an in silico approach was undertaken. Such study revealed that annonacin, seem to target P-type ATPase pump family, that include the sodium potassium ATPase (NKA) and Sarco/endoplasmic reticulum calcium ATPase (SERCA) family members. Furthermore, the in silico data was validated by showing that annonacin is indeed a potent inhibitor of NKA and SERCA pumps. Moreover, annonacin also reduced tumor growth in a xenograft cancer model. Finally, bioinformatics analysis showed strong correlation between NKA or SERCA expressions in cancer patient’s survival. Overall, this study strongly suggests that annonacin targets both the NKA and SERCA pumps as novel pathways for cancer treatment
