Attenuating Effect of Gossypol on Tumor Growth in Systemic Malignancies

Kapoor, Shailendra

doi:10.1007/s12013-013-9673-x

Cited by 7 publications

(3 citation statements)

References 7 publications

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“…Gossypol is as a Bcl-2 homology domain 3 (BH3)-mimetic inhibitor of antiapoptotic Bcl-2 family members, including Bcl-2, Bcl-xL and Mcl-1, and induces apoptosis in various types of cancer ( 2 – 4 ). Gossypol also mediates a number of signaling pathways, including inhibiting the growth of prostate cancer cells by modulation of the TGF-β/Akt signaling pathway ( 5 ) and activation of TP53 ( 6 ), and enhancement of radiation-induced apoptosis through the SAPK/JNK pathway ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

Preparation of novel (-)-gossypol nanoparticles and the effect on growth inhibition in human prostate cancer PC-3 cells in vitro

Jin

Chen

Wáng

et al. 2015

Experimental and Therapeutic Medicine

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The aim of the present study was to investigate the antitumor effects and possible mechanism of (-)-gossypol nanoparticles, loaded with vv polyethylene glycol-maleimide (mPEG-Mal), in vitro. Emulsification-volatilization was used to prepare the loaded (-)-gossypol nanoparticles. The toxicity of blank nanoparticles on human prostate cancer PC-3 cells and human prostate RWPE-1 cells was measured. The antitumor effects of the nanoparticles on PC-3 cells were evaluated by an MTT assay, acridine orange staining and transmission electron microscopy in vitro, and the results were compared with those of free (-)-gossypol. In addition, the mRNA expression levels of Bcl-2 and Bak were measured using semi-quantitative reverse transcription polymerase chain reaction. The growth inhibition activity of the loaded (-)-gossypol nanoparticles was found to be dose- and time-dependent, and similar to the activity of free (-)-gossypol. The nanoparticles induced apoptotic morphological changes on the PC-3 cells, downregulating the mRNA expression level of Bcl-2 and upregulating the mRNA expression level of Bak. Blank nanoparticles exhibited no evident toxicity on PC-3 and RWPE-1 cells at a high dose. Therefore, the mPEG-Mal loaded (-)-gossypol nanoparticles demonstrated a favorable antitumor activity and no toxicity. The nanoparticles were able to induce the apoptosis of prostate cancer cells; thus, may be a potential antitumor nanodrug.

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Section: Introductionmentioning

confidence: 99%

Preparation of novel (-)-gossypol nanoparticles and the effect on growth inhibition in human prostate cancer PC-3 cells in vitro

Jin

Chen

Wáng

et al. 2015

Experimental and Therapeutic Medicine

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“…As the exclusive repository of toxic gossypol, pigment glands contribute to the resist of cotton against pathogens, pests, herbivores, and abiotic stresses [ 50 , 51 , 52 ]. However, the presence of toxic gossypol hinders the utilization of cottonseed rich in protein and oil.…”

Section: Discussionmentioning

confidence: 99%

Comparative Transcriptome Analysis Revealed Key Genes Regulating Gossypol Synthesis in Tetraploid Cultivated Cotton

Kong

Qian

et al. 2023

Genes

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Tetraploid cultivated cotton (Gossypium spp.) produces cottonseeds rich in protein and oil. Gossypol and related terpenoids, stored in the pigment glands of cottonseeds, are toxic to human beings and monogastric animals. However, a comprehensive understanding of the genetic basis of gossypol and gland formation is still lacking. We performed a comprehensive transcriptome analysis of four glanded versus two glandless tetraploid cultivars distributed in Gossypium hirsutum and Gossypium barbadense. A weighted gene co-expression network analysis (WGCNA) based on 431 common differentially expressed genes (DEGs) uncovered a candidate module that was strongly associated with the reduction in or disappearance of gossypol and pigment glands. Further, the co-expression network helped us to focus on 29 hub genes, which played key roles in the regulation of related genes in the candidate module. The present study contributes to our understanding of the genetic basis of gossypol and gland formation and serves as a rich potential source for breeding cotton cultivars with gossypol-rich plants and gossypol-free cottonseed, which is beneficial for improving food safety, environmental protection, and economic gains of tetraploid cultivated cotton.

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“…In addition, gossypol has been identified to reduce the activity of DNA polymerase α and β, inhibit DNA synthesis and block the cell cycle in the S phase, thus indicating gossypol as a specific inhibitor of DNA synthesis (31). Certain studies have reported that gossypol does not appear to alter the cell cycle (32,33), however, these discrepancies are speculated to be due to the impact of gossypol on the cell cycle being cell type-specific, or due to differences among gossypol and its derivatives.…”

Section: Discussionmentioning

confidence: 99%

Combination of L-gossypol and low-concentration doxorubicin induces apoptosis in human synovial sarcoma cells

Baoleri

Dong

Zhou

et al. 2015

Molecular Medicine Reports

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The current study aimed to investigate the function of L-gossypol and low‑concentration doxorubicin (LCD) in the apoptosis of SW982 human synovial sarcoma cells (HSSCs). Wright‑Giemsa staining, Hoechst 33258 staining and transmission electron microscopy were used to identify cellular morphological alterations. In addition, an MTT assay was performed to measure the inhibitory rate of the drug, flow cytometry was used to detect alterations in apoptosis and the cell cycle, and western blot analysis was used to detect Bcl‑2 and Bax protein expression levels. Furthermore, the activity levels of caspase‑3 and ‑9 were measured in apoptotic cells. Following combination therapy, significant alterations in cellular morphology were observed, including condensation of the nucleus and formation of apoptotic bodies. Cell growth was demonstrated to be inhibited significantly in a dose‑ and time‑dependent manner. Flow cytometry results indicated that L‑gossypol administration resulted in G1 phase arrest, whereas doxorubicin led to S phase arrest. Combination therapy resulted in a significant increase in the number of S phase‑arrested cells. Following treatment with the drugs, Bcl‑2 protein levels were observed to be reduced whilst Bax levels increased, and significant caspase‑3 and ‑9 activation was observed during combination therapy. Combination therapy with L‑gossypol and LCD inhibited cell proliferation and induced apoptosis in SW982 HSSCs at a significantly greater level compared with either treatment alone. It was hypothesized that these effects are mediated via downregulation of the Bcl-2 protein and upregulation of Bax protein.

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Attenuating Effect of Gossypol on Tumor Growth in Systemic Malignancies

Cited by 7 publications

References 7 publications

Preparation of novel (-)-gossypol nanoparticles and the effect on growth inhibition in human prostate cancer PC-3 cells in vitro

Preparation of novel (-)-gossypol nanoparticles and the effect on growth inhibition in human prostate cancer PC-3 cells in vitro

Comparative Transcriptome Analysis Revealed Key Genes Regulating Gossypol Synthesis in Tetraploid Cultivated Cotton

Combination of L-gossypol and low-concentration doxorubicin induces apoptosis in human synovial sarcoma cells

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