Antispermatogenic action of gossypol in men

Coutinho, Elsimar Metzker; Melo, José Roberto Tude; Barbosa, Ione Cristina; Segal, Sheldon J.

doi:10.1016/s0015-0282(16)48084-2

Cited by 59 publications

(17 citation statements)

References 9 publications

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“…It has been used traditionally to treat bronchitis and to induce abortion and menses, and in the 1970s its male contraceptive properties, including reversible inhibition of spermatogenesis, were identified. 13 Tolerability studies have identified the optimal oral dosage of gossypol to be 20 mg per day. Its use appears to be limited, however, by a 9.9% chance of development of permanent aspermia and hypokalemia which has been observed in 0.75% of cases.…”

Section: Discussionmentioning

confidence: 99%

Synergistic cytotoxicity of Bcl-xL inhibitor, gossypol and chemotherapeutic agents in non-Hodgkin’s lymphoma cells

Li¹,

Jiang²,

Zhu³

et al. 2008

Cancer Biology & Therapy

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Anti-apoptotic proteins Bcl-2 and Bcl-xL are overexpressed in 80% of non-Hodgkin's lymphoma cells and are thought to play an important role in the resistance of lymphoma cells to current chemotherapeutic agents. Gossypol, an orally-active polyphenolic aldehyde derived from the cotton plant, has been known to have potential anti-neoplastic activity. Recently, gossypol was found to bind to the BH3 binding groove of Bcl-xL and with lesser affinity to Bcl-2. The present study was conducted to determine whether gossypol increases the sensitivity of non-Hodgkin's lymphoma cells to the actions of chemotherapeutic agents by potentiating treatment-induced apoptosis. The interactions observed between gossypol and chemotherapeutic drugs were analyzed using the median effect principle (CalcuSyn analysis). Our data showed that treatment of Ramos cells with gossypol not only induced cell arrest on the G 0 /G 1 phase, but also augmented apoptosis and growth inhibition induced by etoposide (VP-16), doxorubicin hydrochloride (ADM), vincristine (VCR), and paclitaxel (taxol). However, when gossypol was combined with cisplatin (DDP) an antagonistic effect was observed. Gossypol-induced cell cycle arrest was accompanied by decreased expression of cyclin D1 in Ramos cells. In addition, the peroxisome proliferator-activated receptor (PARP) pathway is, at least in part, involved in the gossypolinduced apoptosis when combined with VP-16. These data indicate that single-agent gossypol is effective in inhibiting growth of non-Hodgkin's lymphoma cells in vitro and combination studies with certain secondary chemotherapeutic agents further demonstrate it's synergistic cytotoxicity. These findings support future preclinical and clinical studies of gossypol in the treatment of nonHodgkin's lymphoma.

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Section: Discussionmentioning

confidence: 99%

Synergistic cytotoxicity of Bcl-xL inhibitor, gossypol and chemotherapeutic agents in non-Hodgkin’s lymphoma cells

Li¹,

Jiang²,

Zhu³

et al. 2008

Cancer Biology & Therapy

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“…, 1987 ). In a study on 12 Brazilian men given gossypol monoacetic acid at the recommended contraceptive regime for 12 months, all men achieved azoospermia by 4 months; on discontinuation of treatment, six men recovered to pretreatment levels of sperm concentration, two men recovered to only 50% and remained at this level for 2 years, and four men remained azoospermic, one recovering spermatogenesis progressively during 3 years after discontinuation ( Coutinho et al ., 1984 ; Coutinho & Melo, 1988). Thus, an incidence of 25% irreversible sterility was observed in this study.…”

Section: Reversibility: the Risk Of Permanent Sterility And Long‐termmentioning

confidence: 99%

“…Other articles have traced the reaction to the revelation that 8806 men had been given gossypol by mouth to achieve dramatic suppression of sperm production, apparently without major adverse effects ( Prasad & Diczfalusy, 1982). Even as some of the clinical investigators in China were expressing concern about the incidence of hypokalaemia in the men taking part in these trials ( Qian et al ., 1980 ; Qian & Wang, 1984), reports of small‐scale clinical studies outside China, in Austria ( Frick et al ., 1981 ) and in Brazil ( Coutinho, 1982; Coutinho et al ., 1984 ), began to appear.…”

Section: Introductionmentioning

confidence: 99%

Gossypol: reasons for its failure to be accepted as a safe, reversible male antifertility drug

1998

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Following clinical trials conducted in China in the 1970s, gossypol was proposed as a drug for male contraceptive use. This review summarizes the extensive investigations on formal animal toxicology and on the recovery of fertility in men after stopping gossypol treatment which led to the decision by the Special Programme of Research, Development and Research Training in Human Reproduction (HRP) at the World Health Organization (WHO), that gossypol would not be acceptable as an antifertility drug. It is concluded that the assessment of gossypol reinforces the mandatory requirement that future contraceptive drugs must be developed by the established routes of appropriate animal toxicology and phased clinical studies.

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“…Basierend auf den Erfahrungen wurden auch ausserhalb von China einige Studien mit Gossypol begonnen, um über die Dosis, Effektivität und Seiteneffekte entsprechende Informationen zu bekommen [15][16][17].…”

Section: Gossypolunclassified