Parameters of Reserpine Analogs That Induce MSH2/MSH6-Dependent Cytotoxic Response
Figure 6
(a) Derivatives of reserpine and rescinnamine diminish cell viability in an MSH2-independent manner as shown by MTS assays with an exception of 3,4-dimethoxy reserpine, which demonstrates a slight dependence on MSH2. Evodiamine has an insignificant effect on cell viability. One representative from each of the predicted binding mode groups is shown. MSH2-deficient cells (■) and MSH2-proficient (▴) cell response is shown. (b) Caspase-3 cleavage was assessed in Hec59 (MSH2-deficient; left panel) and Hec59(2) (MSH2-proficient; right panel) cells when treated with various compounds. The 17 and 19 kDa cleavage products of caspase-3 are depicted. Staurosporine (STS) was used as a positive control; actin was used as a loading control. Lisinopril is an ACE inhibitor, like rescinnamine, and demonstrates rescinnamine’s action as being independent of its antihypertensive properties.
