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An in Vitro and in Vivo Study of Antitumor Effects of Gossypol on Human SW-13 Adrenocortical Carcinoma

Developmental Endocrinology Branch, National Institute of Child Health and Development, Bethesda, Maryland 20892

The present study investigated the in vitro and in vivo antitumor effects of gossypol on human SW-13 adrenocortical carcinoma cells. In vitro gossypol concentrations 0.5 µM reduced the growth rate of the Sw-13 cells. Membrane microviscosity was determined by fluorescence polarization of diphenylhexatriene. The membranes of viable SW-13 cells exposed to gossypol became more rigid after a 1-day exposure to gossypol, the polarization constant, P, increasing from 0.229 to 0.352. Gossypol also increased the microviscosities of isolated mitochondrial and microsomal enriched membrane preparations. Tumor was also transplanted into nude mice by s.c. injection of SW-13 cells. A 1-week pretreatment period followed by daily administration of gossypol in which 30 mg gossypol/kg body weight/day was administered via orogastric tube delayed the onset of visible tumor in the subsequent weeks. Five weeks after transplantation, tumor prevalence rate was 95.8% in the control group and 54.5% in the gossypol-treated group. A second experiment, consisting of 12 weeks of gossypol treatment, reduced a preexisting 71% tumor prevalence to 54% while the tumor prevalence increased to 83% in the control group. This was accompanied by a 41.6% mortality in the control group versus 8.3% in the gossypol-treated group. These data suggest that gossypol may provide a beneficial effect in patients with adrenocortical carcinoma.

¹ Supported in part by a grant from the Diabetes Research and Education Foundation.

² Supported by a fellowship from the Medical Research Council of Canada.

³ To whom requests for reprints should be addressed, at Developmental Endocrinology Branch, NICHD, NIH, Building 10/Room 10N262, 9000 Rockville Pike, Bethesda, MD 20892.

Received 12/ 5/88. Revised 3/31/89. Accepted 4/14/89.