Extract of Solanum muricatum (Pepino/CSG) inhibits tumor growth by inducing apoptosis

Background. Apoptosis, or programmed cell death, is characterized by certai n distinct morphological and biochemical features. Most chemotherapeutic dr ugs exert their anti-tumor effects by inducing apoptosis. Therefore, an eff ective compound inducing apoptosis appears to be a relevant strategy to sup press various human tumors. In a search for tumor inhibitors from various k inds of plants, we found that extracts from Solanum muricatum (CSC) can inh ibit tumor growth both in vivo and in vitro by inducing apoptosis. Material s and Methods. A lyophilized aqueous fr action extracted from Solanum muric atum (CSG(4)) was used in this study. The human cell lines tested include: prostate (PC3, DU145), stomach (MKN45), liver (QCY-7721, SK-HEP-IJ, breast (MDA-MB-435), ovarian (OVCAR), colon (HT29) and lung (NCI-H209) cancer cell s, NHP (prostate), HUVEC (umbilical vein endothelial cell), and WI-38 (lung diploid fibroblasts) normal cells. The cell survival was deter-mined by ei ther Cell Titer MTS cell proliferation kit or trypan blue dye exclusion ass ay. The apoptosis was analyzed by (a) apoptotic morphology by light microsc opy; (b) DNA ladder formation; (c) PARP cleavage assay. Results. a) CSG pos sesses selective cytotoxic activity against all the tumor cell lines being tested. The LD50 value is 561-825 mu g/ml. b) CSG showed a much lower cytot oxity to NHP, HUVEC and WI-38 normal cell lines with LD50 value being 2.8-3 .2 mg/ml, which is 3-6 fold higher than on tumor cells, c) The in vivo stud y demonstrated that injection of CSG (100 mu g) directly into tumor mass ca n reduce the tumor volume dramatically in nude mice inoculated with MKN45 g astric cancer cells. ci) CSG-mediated tumor growth inhibition is through in duction of apoptotic cell death, as manifested by (nj typical apoptotic mor phology; (b) DNA ladder formation; and (c) PARP cleavage assay. Conclusion. Taken together; the present study suggests, for the first time, that CSG m ay represent promising new chemical entity which preferentially targets var ious tumor cells by triggering apoptosis.