Acetate gossypol

Oncol Rep. 2013 Aug;30(2):731-8.

Induction of apoptosis and antitumor effects of a small molecule inhibitor of Bcl-2 and Bcl-xl, gossypol acetate, in multiple myeloma in vitro and in vivo.[Pubmed: 23708869 ]

The aim of the present study was to investigate the induction of apoptosis and antitumor effects of Acetate gossypol in multiple myeloma and the possible mechanism(s) of action.
METHODS AND RESULTS:
Our results showed that Acetate gossypol resulted in a dose- and time-dependent inhibition of multiple myeloma cell proliferation, with an IC50 value to both U266 and Wus1 cells at 2.4, 2.2 μM at 48 h after treatment. Acetate gossypol effectively induced the apoptosis of multiple myeloma cells as demonstrated by typical morphological changes, DNA ladder formation and increase in the percentage of cells in subdiploid peak. Furthermore, colorimetric assays showed activation of both caspase-3 and caspase-9. Bcl-2 and Bcl-xl expression was decreased by 86.5±1.2% and 35.9±3.6%, respectively, after treatment with Acetate gossypol at 25 μmol/l for 24 h. Preliminary studies in vivo showed that a growth inhibition (T/C) of 30.9% (gossypol acetate 40 mg/kg) was obtained in Balb/C mice bearing Wus1 cells. In addition, there was no body weight loss for the treated group in comparison with the vehicle mice.
CONCLUSIONS:
Our results demonstrated that the potent inhibitor of Bcl-2 and Bcl-xl Acetate gossypol had significant antiproliferative and antiapoptotic effects on multiple myeloma cells in vitro and in vivo. Acetate gossypol may represent a promising new anticancer agent with a novel molecular mechanism and warrants further investigation as a single agent, or in combination with other chemotherapeutics, for human multiple myeloma with Bcl-2 overexpression.

Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2009 Oct;31(5):527-32.

Effect of gossypol acetate on proliferation and apoptosis in Raji lymphoblastoid cell line[Pubmed: 19968063 ]

To investigate the effects of gossypol acetate(Acetate gossypol ) on proliferation and apoptosis in Raji lymphoblastoid cells and explore the possible mechanism.
METHODS AND RESULTS:
Trypan blue staining and ethyl thiazolyl diphenyl-tetrazolium bromide (MTT) assay were performed to measure the effect of gossypol acetate on the growth of Raji cells. The morphologic changes were observed with Wright's staining assay. Apoptosis was identified by agarose-gel electrophoresis and annexin V-FITC marked flow cytometry (FCM) analysis. The distribution of cell cycle, apoptosis rate, and Bcl-2 protein expression were analyzed by FCM. Caspase-3 activity was detected by colorimetric assay. Gossypol acetate inhibited proliferation and induced apoptosis of Raji cells at concentration higher than 5 micromol/L. The effects were both dose- and time- dependent. Cycle analysis indicated the alteration of cell cycle and G0/G1 arrest. The activation of Caspase-3 was observed by colorimetric assay. The results of flow cytometry showed that the down-regulation of Bcl-2 protein expression and the activation of Caspase-3 seemed to occur simultaneously.
CONCLUSIONS:
Gossypol acetate can inhibit the growth of Raji cells and induce their apoptosis. The mechanism may be related to the alteration of cell cycle and the down-regulation of Bcl-2 protein expression.

Contraception. 1992 May;45(5):493-509.

Histopathological and biochemical effects of gossypol acetate on pituitary-gonadal axis of male albino rats.[Pubmed: 1623720]

Histopathological and biochemical effects of gossypol acetate (Acetate gossypol,GA) on pituitary-gonadal axis were investigated.
METHODS AND RESULTS:
10 and 25 mg GA/kg were administered orally to sexually mature adult male Wistar rats for 4 and 5 weeks, respectively. STH and LTH/PRL cells showed no significant changes as compared to those of controls while TSH cells showed hypertrophy, hyperplasia and degranulation in both experimental groups. Pituitary FSH, LH/ICSH cells showed progressive regression. Gonosomatic indices of sex accessory glands at 25 mg showed significant reduction in the experimental animals as compared to those of controls. The diameter of seminiferous tubules reduced and azoospermia developed. Sertoli and Leydig cells also regressed. At 10 and 25 mg GA treatment, spermatogenesis ceased at secondary spermatocytes and spermatogonia stages, respectively. Epididymis and prostate regressed. Seminal vesicle showed no significant histological variations as compared to that of control except reduction in secretion. Biochemical observations revealed increased levels of acid phosphatase, fructose and citric acid and significant reduction in glycerylphosphoryl choline in reproductive glands of both experimental groups as compared to those of controls. Possible mechanism of antifertility action of GA is discussed.

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2012 Apr;20(2):229-34.

Effects of gossypol acetate on apoptosis in primary cultured cells from patients with lymphoid leukemia and its synergy with dexamethasone.[Pubmed: 22541072]

To investigate the effects of Acetate gossypol on apoptosis in primary cultured cells from patients with acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL) and its synergistic effect with dexamethasone.
METHODS AND RESULTS:
The apoptosis-inducing effect of Acetate gossypol on primary cultured leukemia cells was analyzed by flow cytometry (FCM). The effect of Acetate gossypol on survival rates of Raji cells and mononuclear cells (MNC) from normal bone marrow were evaluated by MTT assay. After co-treatment with Acetate gossypol and dexamethasone, the apoptosis rate of Raji cells was detected by FCM. The results showed that Acetate gossypol was able to induce apoptosis in primary cultured ALL cells at concentrations of ≥ 5 μmol/L. The effect was concentration and time dependent. No major growth inhibitory effect was observed in MNC from normal bone marrow when they were exposed to Acetate gossypol at concentrations lower than 10 μmol/L. After exposing for 48 and 72 h, the IC(50) of Acetate gossypol for MNC from normal bone marrow was 7.1 and 9.1 times as much as the IC(50) of Raji cells. Co-treatment with 10 μmol/L Acetate gossypol and dexamethasone remarkably increased the apoptosis rate of Raji cells.
CONCLUSIONS:
It is concluded that the Acetate gossypol has apoptosis-inducing activity in primary cultured leukemia cells from patients diagnosed as ALL and CLL in vitro. The inhibitory effect of Acetate gossypol on MNC from normal bone marrow is less prominent than that on Raji cells. Co-treatment with Acetate gossypol and dexamethasone notably amplified the pro-apoptosis activity of the latter in Raji cells.

J Androl. 1985 Jan-Feb;6(1):45-52.

Effect of gossypol acetate on guinea pig epididymal spermatozoa in vivo and their susceptibility to capacitation in vitro.[Pubmed: 3972719]

METHODS AND RESULTS:
To determine the effects of gossypol acetate(Acetate gossypol ) on guinea pig epididymal and vas deferens sperm maturity and in vivo susceptibility to in vitro capacitation and the acrosome reaction, we examined spermatozoa removed from 37 animals fed gossypol acetate (10-15 mg/kg/day) for 5 to 9 weeks, and 15 vegetable oil-fed, age-paired control animals. In gossypol-treated, reproductively immature guinea pigs, the number of spermatozoa in the epididymis was markedly reduced (P less than 0.01) compared to controls, whereas the presence of spermatids and spermatocytes increased in the epididymis with the duration of gossypol administration. In sexually mature guinea pigs (given 15 mg/kg/day for 5 weeks), the epididymal sperm survival and forward motility were decreased significantly (P less than 0.025 and P less than 0.01, respectively), although the density of mature spermatozoa was the same as in control animals. The percentage of induced acrosome reactions (26.4 +/- 12%) was almost three-fold lower than that of control animals (72.8 +/- 4.6%). Also, in 31.5 +/- 3.8% of spermatozoa from gossypol-treated animals, as compared to only 2.4 +/- 0.7% of controls, the cytoplasmic droplet failed to migrate to its proper position in the midpiece and was retained in the neck region. With a few exceptions, spermatozoa from both experimental and control groups had comparable patterns of freeze-fractured membrane differentiations. Susceptibility to the induced acrosome reactions and the position of the retained cytoplasmic droplet reversed within 3 weeks after the end of gossypol feeding.
METHODS AND RESULTS:
This study helps establish the suitability of the guinea pig for studies on gossypol-induced infertility.