Growth Inhibition and Apoptosis Induction of Human Umbilical Vein Endothelial Cells by Apogossypolone

Zhan, Yonghua; Huang, Xiaofeng; Hu, Xingbin; An, Qing; Liu, Zhixin; Zhang, Xianqing

doi:10.7314/apjcp.2013.14.3.1791

Cited by 3 publications

(4 citation statements)

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“…Apogossypolone (ApoG2) is a novel derivative of gossypol, which is a polyphenolic substance extracted from cottonseed (7). ApoG2 is an effective inhibitor of cancer cell proliferation and suppresses tumor growth by inducing apoptosis (7).…”

Section: Introductionmentioning

confidence: 99%

“…ApoG2 is an effective inhibitor of cancer cell proliferation and suppresses tumor growth by inducing apoptosis (7). Additionally, ApoG2 is less toxic to normal cells than gossypol.…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, ApoG2 is less toxic to normal cells than gossypol. In laboratory and clinical studies, ApoG2 has shown potent antitumor activity for several types of malignant tumors including prostate (7), breast (8), gastric (9) and pancreatic cancer (10), myeloma (11) and chronic lymphocytic leukemia (12). Several studies have now demonstrated that ApoG2 induces tumor cell apoptosis by blocking the B-cell lymphoma-2 (Bcl-2) signaling pathway (13,14).…”

Section: Introductionmentioning

confidence: 99%

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Apogossypolone induces apoptosis and autophagy in nasopharyngeal carcinoma cells in an in vitro and in vivo study

et al. 2017

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Nasopharyngeal carcinoma (NPC) has a high incidence and mortality rate, particularly in Southern China. Apogossypolone (ApoG2) is a novel derivative of gossypol with antitumor activity and less toxicity. The human NPC CNE-2 cell line was studied in the in vitro model; whilst 4 week-old male nude mice (BALB/c-nu) were inoculated subcutaneously with CNE-2 cells, and xenograft tumors were studied in the in vivo model. Graded concentrations of ApoG2 were used in treatment studies. In ApoG2-treated and control in vitro and in vivo tumor cells, cell apoptosis, and autophagy were evaluated and quantified using fluorescent and transmission electron microscopy and flow cytometry. Hoechst-33258 fluorescence staining was used to evaluate apoptosis in treated and non-treated cell culture and xenograft NPC cells. Western blotting was performed on lysed tumor cells using primary antibodies to B-cell lymphoma-2 (Bcl-2), beclin-1, and β-actin, and flow cytometry results indicated cell apoptosis rates of 3.90±0.34 and 19.52±1.18% in the control and ApoG2-treated cells, respectively (F=485.294, P<0.001). Western blot analysis showed that ApoG2 significantly decreased expression of the Bcl-2 protein in CNE-2 cells, when compared with control cells (F=68.909, P=0.001) and flow cytometry showed cell autophagy rates of 0.92±3.10% of control cells compared with 28.24±7.35% of ApoG2-treated cells (F=31.035, P=0.003). ApoG2 treatment significantly increased beclin-1 protein expression in CNE-2 cells (F=497.906, P<0.001). ApoG2 treatment inhibited NPC xenograft tumor growth by 65.49% (P<0.05). In conclusion, these results support a role for ApoG2 in inhibiting the growth of human NPC cells by inducing apoptosis and autophagy. Future controlled clinical studies could be planned, to define safety, efficacy and dosing regimens for ApoG2 as a potential treatment for patients with NPC.

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Section: Introductionmentioning

confidence: 99%

“…ApoG2 is an effective inhibitor of cancer cell proliferation and suppresses tumor growth by inducing apoptosis (7). Additionally, ApoG2 is less toxic to normal cells than gossypol.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Apogossypolone induces apoptosis and autophagy in nasopharyngeal carcinoma cells in an in vitro and in vivo study

et al. 2017

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“…Furthermore, (±)-gossypol can bind to Bcl-2, Bcl-xL, and Mcl-1, which suggests that (±)-gossypol might be an alternative treatment approach associated with apoptosis (Shen et al 2018). Zhan et al (2013) have demonstrated that apogossypolone, a gossypol derivative, induces apoptosis by inhibiting the growth and angiogenesis of HUVECs. Studies have also shown that (±)-gossypol has anti-proliferative effects on various cancer cell lines, such as MCF-7 human breast cancer cells (Jaroszewski et al 1990); PC3 human prostate cancer cells (Jiang et al 2004); WM164, WM56, and WM9 human melanoma cells; human ovarian cancer cells (Wang and Rao 1984); and SW1116, SW1084, and SW407 colon carcinoma cells (Tuszynski and Cossu 1984).…”

Section: Introductionmentioning

confidence: 99%

The anti-angiogenic potential of (±) gossypol in comparison to suramin

et al. 2018

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Cotton, a staple fiber that grows around the seeds of the cotton plants (Gossypium), is produced throughout the world, and its by products, such as cotton fibers, cotton-seed oil, and cottonseed proteins, have a variety of applications. Cotton-seed contains gossypol, a natural phenol compound. (±)-Gossypol is a yellowish polyphenol that is derived from different parts of the cotton plant and contains potent anticancer properties. Tumor growth and metastasis are mainly related to angiogenesis; therefore, anti-angiogenic therapy targets the new blood vessels that provide oxygen and nutrients to actively proliferating tumor cells. The aim of the present study was to evaluate the anti-angiogenic potential of (±)-gossypol in vitro. (±)-Gossypol has anti-proliferative effects on cancer cell lines; however, its anti-angiogenic effects on normal cells have not been studied. Anti-proliferative activities of gossypol assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, anti-angiogenic activities using tube formation assay, and cell migration inhibition capability using a wound-healing assay on human umbilical vein endothelial cells (HUVECs) were revealed. (±)-Gossypol displayed the following potent anti-angiogenic activities in vitro: it inhibited the cell viability of HUVECs, it inhibited the migration of HUVECs, and disrupted endothelial tube formation in a dose-dependent manner. In addition, the anti-angiogenic effects of (±)-gossypol were investigated in ovo in a model using a chick chorioallantoic membrane (CAM). Decreases in capillary density were assessed and scored. (±)-Gossypol showed dose-dependent anti-angiogenic effects on CAM. These findings suggest that (±)-gossypol can be used as a new anti-angiogenic agent.

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In vitro Study of the Antagonistic Effect of Low-dose Liquiritigenin on Gemcitabine-induced Capillary Leak Syndrome in Pancreatic Adenocarcinoma via Inhibiting ROS-Mediated Signalling Pathways

Wu¹,

Xia²,

Luo³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Growth Inhibition and Apoptosis Induction of Human Umbilical Vein Endothelial Cells by Apogossypolone

Cited by 3 publications

References 31 publications

Apogossypolone induces apoptosis and autophagy in nasopharyngeal carcinoma cells in an in vitro and in vivo study

Apogossypolone induces apoptosis and autophagy in nasopharyngeal carcinoma cells in an in vitro and in vivo study

The anti-angiogenic potential of (±) gossypol in comparison to suramin

In vitro Study of the Antagonistic Effect of Low-dose Liquiritigenin on Gemcitabine-induced Capillary Leak Syndrome in Pancreatic Adenocarcinoma via Inhibiting ROS-Mediated Signalling Pathways

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