There is a growing interest regarding the use of camptothecins (CPTs) for the management of
ovarian cancer. Since
topoisomerase I has been established as a prime target of these drugs in other experimental models, it was important to determine whether sensitivity to CPTs in
ovarian cancer cells is also correlated with the cellular level of this
enzyme. Despite the 7-fold increase in topoisomerase expression achieved by adenovirus-mediated expression, the sensitivity to a
CPT derivative (
topotecan), was not improved compared with control cells harboring an endogenous level of the
enzyme. This observation is in accordance with the similar level of
topoisomerase I activity found in control and overexpressing cells and suggests that these cells may efficiently regulate the
enzyme activity. Indeed,
topoisomerase I overexpressing cells are characterized by a lack of
alkaline phosphatase sensitivity and elimination of the hyperphosphorylated form of the
protein. Taken together, these observations strongly suggest that an alteration in the phosphorylation state of
topoisomerase I could limit its activity and prevent improvement of
CPT response in
ovarian cancer cells. In addition, a limited extent of
topoisomerase I phosphorylating activity was found in nuclear extract of OVCAR-3 cells. Hence, providing enhancement in
topoisomerase I expression may not result in improvement of
CPT response in
ovarian cancer cells because of an efficient control of the phosphorylation state of the
enzyme.