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Departments of Radiation Oncology [J. J. M., R. L. J.] and Surgery [R. S. C.], Duke University Medical Center, Durham, North Carolina 27710; Department of Human Oncology, University of Wisconsin-Madison, Madison, Wisconsin 53792 [M. N. G.]; and MITRE Corp., Inc., McLean, Virginia 22102-348 [I. J. B.]
The monoterpenes d-limonene and perillyl alcohol (POH) inhibit the growth of mammary tumors. In this investigation we tested whether POH is also effective in reducing liver tumor growth. Diethylnitrosamine was used to induce liver tumors in male Fischer 344 rats. Two weeks after diethylnitrosamine exposure was discontinued, the animals were divided into POH-treated and untreated groups. The mean liver tumor weight for the POH-treated rats after 19 weeks of POH treatment was 10-fold less than that for the untreated animals. POH did not influence tumor cell proliferation but increased the apoptotic index approximately 10-fold. The mRNA levels for the mannose 6-phosphate/insulin-like growth factor II receptor and the transforming growth factor ß type I, II, and III receptors were also significantly increased in the liver tumors from the POH-treated animals when compared to the corresponding receptor mRNA levels in the normal tissue surrounding the tumors and in the tumors of untreated animals. These results demonstrate that POH does not promote the formation of liver tumors, but rather inhibits their growth by enhancing tumor cell loss through apoptosis.
1 This work was supported by USPHS NIH Grants CA25951 (R. L. J.) and CA38128 (M. N. G.) and by an ILSI Postdoctoral Fellowship (J. J. M.).
2 To whom requests for reprints should be addressed, at Box 3433, Duke University Medical Center, Durham, NC 27710.
Received 12/ 1/94. Accepted 1/18/95.
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