• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2485-2489
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• 2012

Purpose: Notch is an important signaling pathway that regulates cell fate, stem cell maintenance and the initiation of differentiation in many tissues. It has been reported that activation of Notch-1 contributes to tumorigenesis. However, whether Notch signaling might have a role in chemoresistance of prostate cancer is unclear. This study aimed to investigate the effects of Notch-1 silencing on the sensitivity of prostate cancer cells to docetaxel treatment. Methods: siRNA against Notch-1 was transfected into PC-3 prostate cancer cells. Proliferation, apoptosis and cell cycle distribution were examined in the presence or absence of docetaxel by MTT and flow cytometry. Expression of $p21^{waf1/cip1}$ and Akt as well as activation of Akt in PC-3 cells were detected by Western blot and Real-time PCR. Results: Silencing of Notch-1 promoted docetaxel induced cell growth inhibition, apoptosis and cell cycle arrest in PC-3 cells. In addition, these effects were associated with increased $p21^{waf1/cip1}$ expression and decreased Akt expression and activation in PC-3 cells. Conclusion: Notch-1 promotes chemoresistance of prostate cancer and could be a potential therapeutic target.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.05a
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• pp.9-13
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• 2001

Genistein, a natural isoflavonoid phytoestrogen, is a strong inhibitor of protein tyrosine kinase and DNA topoisomerase II activities. Genistein has been shown to have anticancer proliferation, differentiation and chemopreventive effects. In the present study, we have addressed the mechanism of action by which genistein suppressed the proliferation of p53-null human prostate carcinoma cells.(omitted)

• Radiation Oncology Journal
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• v.17 no.1
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• pp.70-77
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• 1999

Purpose : The expression of p53, P211WAF/CIP, Bcl-2, and Bax underlying the radiation-induced apoptosis in different pH environments using SCK mammary adenocarcinoma cell line was investigated. Materials and Methods Mammary adenocarcinoma cells of hi) mice (SCK cells) in exponential growth phase were irradiated with a linear accelerator at room temperature. The cells were irradiated with 12 Gy and one hour later, the media was replaced with fresh media at a different pHs. After Incubation at 37Microbioiogy, College of Medicine Dong A University for 0$\~$48 h, the extort of apoptosis was determined using agarose gel electrophoresis and flow cytometry. The progression of cells through the cell cycle after irradiation in different pHs was also determined with flow cytometry. Western blot analysis was used to monitor p53, p211WAFfCIP, Bcl-2, and Bu protein levels. Results : The induction of apoptosis by irradiation in pH 6.6 medium was markedly less than that in pH 7.5 medium. The radiation-induced G2IM arrest in pH 6.6 medium lasted markedly longer than that in pH 7.5 medium. Considerable amounts of p53 and p21 proteins already existed at pH 7.5 and increased the level of p53 and p21 significantly after 12 Gy X-irradiation. An incubation at pH 6.6 after 12 Gy X-irradiation did not change the level of p53 and p21 protein levels significantly. Bcl-2 proteins were not significantly affected by radiation and showed no correlation with cell susceptibility to radiation-induced apoptosis in different pHs. An exposure to 12 Gy of X-rays increased the level of Bax protein at pH 7.5 but at pH 6.6, it was slight. Conclusions : The molecular mechanism underlying radiation-induced apoptosis in dinerent pH environments using SCK mammary adenocarcinoma cell line was dependent of the expression p53 and P211YVAF/CIP proteins. We may propose following hypothesis that an acidic stress augments the radiation-induced G2iM arrest, which inhibiting the irradiated cells undergo post-mitotic apoptosis. The effects of environmental acidity on anti-apoptotic and pro-apoptotic function of Bcl-2 family was unclear in SCK mammary adenocarcinoma cell line.

• Proceedings of the Zoological Society Korea Conference
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• 2001.04a
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• pp.88-88
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• 2001

No Abstract, See Full Text

• BMB Reports
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• v.53 no.5
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• pp.272-277
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• 2020

Protein kinase CK2 downregulation induces premature senescence in various human cell types via activation of the reactive oxygen species (ROS)-p53-p21^Cip1/WAF1 pathway. The transcription factor "nuclear factor erythroid 2-related factor 2" (Nrf2) plays an important role in maintaining intracellular redox homeostasis. In this study, Nrf2 overexpression attenuated CK2 downregulation-induced ROS production and senescence markers including SA-β-gal staining and activation of p53-p21^Cip1/WAF1 in human breast (MCF-7) and colon (HCT116) cancer cells. CK2 downregulation reduced the transcription of Nrf2 target genes, such as glutathione S-transferase, glutathione peroxidase 2, and glutathione reductase 1. Furthermore, CK2 downregulation destabilized Nrf2 protein via inhibiting autophagic degradation of Kelch-like ECH-associated protein 1 (Keap1). Finally, CK2 downregulation decreased the nuclear import of Nrf2 by deactivating AMP-activated protein kinase (AMPK). Collectively, our data suggest that both Keap1 stabilization and AMPK inactivation are associated with decreased activity of Nrf2 in CK2 downregulation-induced cellular senescence.

• Proceedings of the Ginseng society Conference
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• 2006.05a
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• pp.3-12
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• 2006

1 The present work was performed to investigate the effects of ginsenoside Rh2 on proliferation, cell cycle-regulation and differentiation of human leukemia HL-60 cells as well as the underlying mechanisms for these effects. 2 Ginsenoside Rh2 potently inhibited the proliferation of HL-60 cells in both a dose- and time-dependent manner with an $IC_{50}$, $20{\mu}M$. 3 DNA flow-cytometry indicated that ginsenoside Rh2 markedly induced a $G_1$ phase arrest of HL-60 cells. 4 Among the $G_1$ phase cell cycle-related proteins, the levels of cyclin-dependent kinase(CDK)4, 6 and cyclin D1, cyclin D2, cyclin D3 were reduced by ginsenoside Rh2, whereas the steadystate levels of CDK2 and cyclin E were unaffected. 5 The protein levels of a CDK inhibitor p16, $p21^{CIP1/WAF1}$ and $p27^{KIP1}$ were markedly increased by ginsenoside Rh2. 6 Ginsenoside Rh2 markedly enhanced the binding of $p21^{CIP1/WAF1}$ and $p27^{KIP1}$ with CDK2 and CDK6, resulting in the reduced activity of both kinases and the hypophosphorylation of Rb protein. 7 We furthermore suggest that ginsenoside Rh2 is a potent inducer of the differentiation of HL-60 cells, based on observations such as a reduction of the nitroblue tetrazolium level, an increase in the esterase activities and phagocytic activity, morphology changes, and the expression of CD11b, CD14, CD64 and CD66b surface antigens. 8 In conclusion, the onset of ginsenoside Rh2-induced the $G_0/G_1$ arrest of HL-60 cells prior to the differentiation is linked to a sharp up-regulation of the $p21^{CIP1/WAF1}$ level and a decrease in the CDK2, CDK4 and CDK6 activities. This is the first report demonstrating that ginsenoside Rh2 potently inhibits the proliferation of human promyelocytic HL-60 cells via the $G_1$ phase cell cycle arrest and differentiation induction.

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.210.1-210.1
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• 2001

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.5
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• pp.2655-2660
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• 2016

Background: Prostate cancer is the second most common male cancer and remains a leading cause of cancer death worldwide. Heterogeneity regarding recurrence, tumor progression and therapeutic response reflects the inadequacy of traditional prognostic factors and underlies interest in new genetic and molecular markers. In this work, we studied the prognostic value of the expression of 9 proteins, Ki-67, p53, Bcl-2, PSA, HER2, E-cadherin, $p21^{WAF1/Cip1}$, $p27^{Kip1}$ and $p16^{ink4a}$ in prostate cancer. Materials and Methods: We conducted a retrospective study of 50 prostate cancers diagnosed in Pathology Department of Farhet Hached Hospital, Sousse, Tunisia, during a period of 12 months. Clinico-pathological data and survival were investigated. Protein expression was analyzed by immunohistochemistry on archived material. Results: Expression or over-expression of Ki-67, p53, Bcl-2, PSA, HER2, E-Cadherin, $p21^{WAF1/Cip1}$, $p27^{Kip1}$ and $p16^{ink4a}$ was observed in 68%, 24%, 32%, 78%, 12%, 90%, 20%, 44% and 56% of cases, respectively. Overall five-year survival was 68%. A statistically significant correlation was observed between death occurrence and advanced age (p=0.018), degree of tumor differentiation (p=0.0001), perineural invasion (p=0.016) and metastasis occurrence (p=0.05). Death occurrence was significantly correlated with the expression of p53 (p=0.007), Bcl-2 (p=0.02), Ki-67 (p=0.05) and $p27^{Kip1}$ (p=0.04). Conclusions: The p53, Bcl-2, Ki-67 and $p27^{Kip1}$ proteins may be useful additional prognostic markers for prostate cancer. The use of these proteins in clinical practice can improve prognosis prediction, disease screening and treatment response of prostatic cancer.

• Journal of Environmental Science International
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• v.16 no.2
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• pp.219-225
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• 2007

Endocrine disrupting compounds (EDC's) are chemicals that either mimic endogenous hormones interfering with pharmacokinetics or act by other mechanisms. Some endocrine disrupters were reported to be chemical substances that cause apoptosis in cells. A number of reports have indicated that 1,3-DCP, one of the EDC's may act as an endocrine disrupter and also has possible carcinogenic effects. 1,3-DCP, present in commercial protein hydrolysates used for human nutrition, are genotoxic and 1,3-dichloro-2-propanol induced tumors in rats. In the present study, it was investigated whether 1,3-DCP induces ROS generation and apotosis in A549 adenocarcinoma cells. Here we show that 1,3-DCP inhibits the growth of lung cancer cell lines and generates reactive oxygen species (ROS), a major cause of DNA damage and genetic instability, It was investigated that 1,3-DCP increases G1 phase cells after 12 hours, thereafter abruptly draws A549 cells to G0 state after 24 hours by flow cytometric analysis. 1,3-DCP induces p53 and $p21^{Cip1/WAF1}$ activation time- and dose-dependently by 24 hours, while the level $p21^{Cip1/WAF1}$ was decreased after 48 hours. These results suggest that 1,3-DCP, an EDC's generates ROS and regulates genes involved with cell cycle and apoptosis.

• Proceedings of the PSK Conference
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• 2000.10a
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• pp.182.2-182.2
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• 2000