Verotoxin induces rapid elimination of human renal tumor xenografts in SCID mice.
OBJECTIVE
Verotoxins (VTs) are subunit toxins produced by enteropathogenic Escherichia coli. The VT receptor glycolipid Gb3, which mediates the cytotoxicity of VTs, has been reported to be elevated on the surface of several tumor cell lines. In this study the effect of VT1 as an antineoplastic agent was assessed using various human urological cancer cell lines.


METHODS
The expression of Gb3 on human cancer cell lines originating from renal cell carcinoma (ACHN, A-704, CAKI-1 and CAKI- 2), prostate cancer (LNCaP and PC3) and testicular tumor (2102Ep) were examined by FACScan (Becton Dickinson, Sunnyvale, California). These cell lines were cultured with various concentrations of VT1 and subjected to microculture tetrazolium dye assay for determination of cell viability. Furthermore, ACHN cells were inoculated into the backs of SCID mice and intratumor injection of VT1 was performed. Pathological samples were examined by hematoxylin and eosin staining as well as by TUNEL assay.


RESULTS
The growth of ACHN, CAKI-1, A-704, 2102Ep and LNCaP but not CAKI-2 and PC3 was significantly inhibited by co-incubation with VT1, as determined by microculture tetrazolium dye assays, consistent with FACScan results for Gb3 expression. When mice bearing ACHN tumors were injected with VT1, rapid reduction in the size of subcutaneous tumors was observed with complete regression within 5 to 7 days. Pathological examination by the TUNEL method indicated that the cytotoxicity of VT1 was mediated by apoptosis.


CONCLUSIONS
These results suggest that VTs could be candidates for antineoplastic agents against Gb3 expressing tumors for clinical use.
Ishitoya
Satoshi
S
Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Kurazono
Hisao
H
Nishiyama
Hiroyuki
H
Nakamura
Eijiro
E
Kamoto
Toshiyuki
T
Habuchi
Tomonori
T
Terai
Akito
A
Ogawa
Osamu
O
Yamamoto
Shingo
S
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy*; D051379:Mice; D016513:Mice, SCID; D022603:Shiga Toxins / Q000627:therapeutic use*; D013997:Time Factors; D023041:Xenograft Model Antitumor Assays
D022603:Shiga Toxins