Aim:

To evaluate the anti-proliferative activity and mitochondrial toxicity of gossypol in endometrioma cells maintained in short-term cultures.

Methods:

(A) Three endometrioma cell lines from patients were treated with 25 or 50 nmol/L gossypol for up to 12 days. The effect of gossypol on the cell growth was recorded. (B) A phosphorescence oxygen analyzer was used to determine the effects of gossypol on mitochondrial oxygen consumption of six endometrioma cell lines from patients. (C) Cellular gossypol accumulations in three endometrioma cell lines from patients were measured by high-pressure liquid chromatography.

Results:

Proliferation of the endometrioma cells was inhibited by 25 and 50 nmol/L gossypol. Respiration of the endometrioma cells was inhibited by 10 mol/L gossypol. Cellular gossypol was detected in the endometrioma cell lines that were treated for 24 h with 10 and 0.3 mol/L gossypol.

Conclusion:

Gossypol invokes a potent toxicity on cultured endometrioma cells.

References

1. Withers WA, Carruth FE. Gossypol-a toxic substance in cottonseed meal. A preliminary note. Science 1915 41: 324.  | Article | PubMed | ChemPort |
2. Poso H, Wichmann K, Janne J, Luukkainen T. Gossypol, a powerful inhibitor of human spermatozoal metabolism. Lancet 1980; 1: 885–6. | Article | PubMed | ChemPort |
3. Tuszynski GP, Cossu G. Differential cytotoxic effect of gossypol on human melanoma, colon cancer, and other tissue culture cell lines. Cancer Res 1984; 44: 768–71. | PubMed | ISI | ChemPort |
4. Wu D. An overview of the clinical pharmacology and therapeutic potential of gossypol as a male contraceptive agent and in gynecological disease. Drugs 1989; 38: 333–441. | PubMed | ChemPort |
5. Bushunow P, Reidenberg MM, Wasenko J, Winfield J, Lorenzo B, Lemke S, et al. Gossypol treatment of recurrent adult malignant gliomas. J Neurooncol. 1999; 43: 79–86.  | Article | PubMed | ChemPort |
6. Benz CC, Keniry MA, Ford JM, Townsend AJ, Cox FW, Palayoor S, et al. Biochemical correlates of the antitumor and antimitochondria properties of gossypol enantiomers. Mol Pharmacol 1990; 37: 840–7.  | PubMed | ChemPort |
7. Qian SZ, Wang ZG. Gossypol: a potential antifertility agent for males. Ann Rev Pharmacol Toxicol 1984; 24: 329–60. | Article | ChemPort |
8. Wang YE, Luo YG, Tang XC. Studies on the antifertility actions of cottonseed meal and gossypol. Document of First National Conference on Male Antifertility Agents, Wuhan (September 1972). Acta Pharm Sin 1979; 14: 662–9.  | ChemPort |
9. Xue SP, Zang SD, Su SY, Wu YW, Lin Y, Zhou ZH, Antifertility effect of gossypol on the germinal epithelium of the rat testis. A cytological, autoradiographical and ultrastructural observation. Document of Second National Conference on Male Antifertility Agents, Qingdao (1973). Sci Siu 1979; 9: 915–28.
10. Xue SP. Studies on the antifertility effect of gossypol, a new contraceptive for males. Symposium on Recent Advances in Fertility Regulation. 2–5 September, Beijing, China. 1980; 122–46.
11. Dai RX, Pang SN, Liu ZL. Studies on the antifertility effect of gossypol. II. A morphological analysis of the antifertility effect of gossypol. Document of Fourth National Conference on Male Antifertility Agents, Suzhou (1975). Acta Biol Exp Siu 1978; 11: 27–36.
12. Han ML, Wang YF, Tang MY, Ge QS, Zhou LF, Zhu PD, et al. Gossypol in the treatment of endometriosis and uterine myoma. Contrib Gynecol Obstet 1987; 268–70.
13. Abou-Donia MB, Dieckert JW. Gossypol: uncoupling of respiratory chain and oxidative phosphorylation. Life Science 1974; 14: 1955–63. | Article | ChemPort |
14. Cuellar A, Ramirez J. Further studies on the mechanism of action of gossypol on mitochondrial membrane. Internat J Biochem 1974; 25: 1149–55. | Article |
15. Petit PX, Zamzami N, Vayssiere JL, Mignotte B, Kroemer G, Castedo M. Implication of mitochondria in apoptosis. Mol Cell Biochem 1997; 174: 185–8. | Article | PubMed | ISI | ChemPort |
16. Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, et al. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell1997; 91: 479–89.  | Article | PubMed | ISI | ChemPort |
17. Badawy SZ, Holland J, Landis S, Frankel L, Cuenca V, Khan S. Role of estradiol, progesterone and transforming factor on human endometrioma cell culture. J Reproductive Immunol 1996; 36: 58–63. | ChemPort |
18. Souid AK, Tacka KA Galvan KA, Penefsky HS. Immediate effects of anticancer drugs on mitochondrial oxygen consumption. Biochem Pharmacol 2003; 66: 977–98. | Article | PubMed | ChemPort |
19. Lo LW, Koch CJ, Wilson DF. Calibration of oxygen-dependent quenching of the phosphorescence of Pd-meso-tetra (4-carboxyphenyl) porphine: a phosphor with general application for measuring oxygen concentration in biological systems. Anal Biochem 1996; 236: 153–60. | Article | PubMed | ChemPort |
20. Marcelle GB, Ahmed MS, Pezzuto JM, Cordell GA, Waller DP, Soejarto DD, et al. Analysis of gossypol and gossypol-acetic acid by high performance liquid chromatography. J Pharm Sci 1984; 3: 396–8.  | Article |
21. Hubei Pronvical Hancuan "Disease of Burning Sensation", Treatment and Prevention Group. Collected material about disease of burning sensation. Document of Conference on Disease of Burning Sensation, Hubei1970.
22. Flack MR, Pyle RG, Mullen NM, Lorenzo B, Wu YW, Knazek RA, et al. Oral gossypol in the treatment of metastatic adrenal cancer. J Clin Endocrinol Metab 1993; 76: 1019–24.  | Article | PubMed | ChemPort |
23. Cheng KF, Wu WY, Tang MY, Chu PT. Endometrial changes after administration of gossypol for menorrhagia. Am J Obstet Gynecol 1980; 138: 1227–9. | PubMed | ChemPort |
24. Liu YX, Jia XC, Zhou SW, Zhou M. Effect of gossypol on the steroid receptors of the endometrium. Chinese J Obstet Gynecol 1981; 16: 129–31. | ChemPort |
25. Xue SP, Liang DC, Fei RR, Chen XM, Ye SJ, Liu Y, et al. Subcellular site of antisprematogenic effect of Gossypol and its possible molecular mechanism of action. Sci Sin (B) 1988; 26: 614–33.