The
tumor suppressor
Fhit protein lost in many human pre-malignant tissues, possesses
diadenosine triphosphate activity regulated by a
photosensitizer,
protoporphyrin IX (
PpIX) in vitro. Interestingly, when exogenously restored, the
protein suppresses the growth of human cervical
carcinoma HeLa cells which is further enhanced by
PpIX. Additionally, Fhit production enhances the overall response of cells to
PpIX-mediated photodynamic reaction. In the present study, we have estimated, for the first time, the
biological activity of two Fhit mutated forms exhibiting aberrant Ap(3)A
hydrolase activity in vitro which emphasizes the recent findings that hydrolysis of Ap(3)A is not necessary for Fhit
tumor suppression function. Using several biophysical methods we revealed the dynamic nature of mutant Fhit-
PpIX complexes in vitro which support our previous hypothesis that Fhit-Ap(3)A-PpIX might be a signaling molecule driving apoptosis in
cancer cells. Moreover, according to our findings, substitution at histidine94 in Fhit active site induces the vulnerability of HeLa cells to
PpIX-
PDT in a similar manner to that caused by wild-type
Fhit protein. These results support the view that inhibition of Fhit
hydrolase activity might be a crucial
element in a Fhit-driven
cancer cells death.