Extract of Solanum muricatum (Pepino/CSG) inhibits tumor growth by inducing apoptosis.
BACKGROUND
Apoptosis, or programmed cell death, is characterized by certain distinct morphological and biochemical features. Most chemotherapeutic drugs exert their anti-tumor effects by inducing apoptosis. Therefore, an effective compound inducing apoptosis appears to be a relevant strategy to suppress various human tumors. In a search for tumor inhibitors from various kinds of plants, we found that extracts from Solanum muricatum (CSG) can inhibit tumor growth both in vivo and in vitro by inducing apoptosis.


METHODS
A lyophilized aqueous fraction extracted from Solanum muricatum (CSG4) was used in this study. The human cell lines tested include: prostate (PC3, DU145), stomach (MKN45), liver (QGY-7721, SK-HEP-1), breast (MDA-MB-435), ovarian (OVCAR), colon (HT29) and lung (NCI-H209) cancer cells; NHP (prostate), HUVEC (umbilical vein endothelial cell), and WI-38 (lung diploid fibroblasts) normal cells. The cell survival was determined by either Cell Titer MTS cell proliferation kit or trypan blue dye exclusion assay. The apoptosis was analyzed by (a) apoptotic morphology by light microscopy; (b) DNA ladder formation; (c) PARP cleavage assay.


RESULTS
a) CSG possesses selective cytotoxic activity against all the tumor cell lines being tested. The LD50 value is 561-825 micrograms/ml. b) CSG showed a much lower cytotoxicity 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 study demonstrated that injection of CSG (100 micrograms) directly into tumor mass can reduce the tumor volume dramatically in nude mice inoculated with MKN45 gastric cancer cells. d) CSG-mediated tumor growth inhibition is through induction of apoptotic cell death, as manifested by (a) typical apoptotic morphology; (b) DNA ladder formation; and (c) PARP cleavage assay.


CONCLUSIONS
Taken together, the present study suggests, for the first time, that CSG may represent promising new chemical entity which preferentially targets various tumor cells by triggering apoptosis.
Ren
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Virotech Canada Inc., Windsor, ON, Canada. wpren@mnsi.net
Tang
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D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010936:Plant Extracts / Q000494:pharmacology; D010946:Plants, Medicinal; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000473:pathology; D014407:Tumor Cells, Cultured
D016588:Anticarcinogenic Agents; D010936:Plant Extracts