• Herbal Formula Science
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• v.29 no.4
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• pp.267-275
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• 2021

Objectives : Previously, we reported that compound K isolated from fermented ginseng by Aspillus oryzae has a wide biochemical and pharmacological effect, including anti-cancer activity in prostate cancer PC-3 cells. Despite these findings, its signaling pathway and gene expression pattern are not clearly understood. Methods : To confirm the gene expression study of treated with compound K in PC-3 cells, a cDNA microarray chip composed of 44K human cDNA probes was used. MTT assay, western blot analysis, propidium iodide staining, and annexin V/propidium iodide staining were analyzed. Results : We confirmed the differences of gene expression profiles. Then, we analyzed with the cell cycle arrest, cell death and cell proliferation related genes using DAVID database. Conclusions : Our finding should be useful for understanding genome-wide expression patterns of compound K-mediated cell cycle arrest toward induction of cell death and be helpful for finding future cancer therapeutic targets for prostate cancer cells.

• Journal of Nutrition and Health
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• v.41 no.3
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• pp.224-231
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• 2008

We examined the effect of indole-3-carbinol (I3C, $C_9H_9NO$), an autolysis product of a glucosinolate and a glucobrassicin in vegetables, on MMP-2, -9 activities and TIMP-l and -2 inductions via microtubule-associated protein kinase (MAPK) signaling pathway in prostate cancer cell line, PC3 cells. Our results indicated that I3C inhibited cell growth of PC3 cells in dose (0,50, 100 ,${\mu}M$) and time (0,24,48 and 72 h) dependent manners. Using gelatin zymography for MMP activity, we demonstrated that I3C significantly decrease MMP-2 and -9 activities in PC3 cells. We also observed that I3C decreased the proteins and mRNA levels of MMP-2 and -9 in PC3 cells as well. Inversely, expressions of TIMP-l and -2 protein and mRNA in PC3 cells were increased by I3C in a dose dependent manner. In another experiment, we showed that I3C inhibited PC3 cells invasiveness by using marigel invasion assay and we also found that I3C suppressed MMP transcriptional activity by MAPK signaling pathways. Taken together, our results suggest that I3C may contribute to the potential beneficial food component to prevent the cancer metastasis in prostate cancer cells. (KoreanJNutr2008; 41(3): 224~23I)

• Korean Journal of Acupuncture
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• v.24 no.2
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• pp.163-184
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• 2007

Objectives & Methods : The purpose of this study is to observe the effects of Phellodendri Cortex Herbal-acupuncture solution (PC-HAS) at Joksamni (ST36) on collagen II induced arthritis in DBA-1J mice. The author performed several experimental items to analyze arthritis evaluation, change of weight, spleen size and adhesion rate, change of cytokine level, IgG, IgM and anti-collagen II, chang of immunocyte count, histological change of CIA mouse joint. Results : 1. In the PC-HA group, arthritis index, the incidence of arthritis and joint edema were significantly decreased. 2. In the PC-HA group, the change of spleen size, spleen adhesion rate and the knee joint were significantly decreased. 3. The levels of $IL-1{\beta}$, IL-6 and INF- in serum of the CIA mouse were significantly decreased by PC-HA. 4. The levels of IgG, IgM and anti-collagen II in serum of the CIA mouse were significantly decreased by PC-HA. 5. In the CIA mouse spleen cell culture, the levels of IFN- , IFN- / IL-4, IL-10 were significantly decreased by PC-HA, but the level of IL-4 was significantly increased by PC-HA. 6. In the PC-HA group, the ratios of $CD3e^+$ to $CD45R^+$ cell, $CD4^+$ to $CD8^+$ cell and $CD4^+/CD25^+$ cell were similarly maintained as normal group in the CIA mouse spleen cell. 7. In the PC-HA group, $CD4^+CD25^+$ and $CD45R^+/CD69^+$ cell were significantly decreased in the lymph nodes. 8. In the PC-HA group, $CD3^+/CD69^+$ and $CD11b^+/Gr-1^+$ cell were significantly decreased in knee joint. 9. In histology, the cartilage destruction and synovial cell proliferation in the PC-HA group were similar with that of the normal group and the collagen fiber expressions in the PC-HA group were similar with that of the normal group. Conclusions : Form the result above, the results suggest that the PC-HA at ST36 has significant effect on collagen-induced arthritis, and can be put to practical use in the future rheumatoid arthritis clinic.

• Journal of Life Science
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• v.23 no.6
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• pp.832-837
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• 2013

In this study, it was investigated the possible mechanisms by which glutamine deprivation exerts its anti-proliferative action in cultured human prostate carcinoma PC3 cells. Glutamine deprivation resulted in inhibition of growth and G2/M arrest of the cell cycle in a time-dependent manner without apoptosis induction, as determined by MTT assay, DAPI staining and flow cytometry analyses. The induction of G2/M arrest by glutamine deprivation was associated with the inhibition of expression of Cdc2, cyclin A and cyclin B1, and up-regulation of the expression of cyclin-dependent kinase (Cdk) inhibitor p21(WAF1/CIP1) in both transcriptional and translational levels. Moreover, glutamine deprivation increased the phosphorylation of checkpoint kinase (Chk)1 and Chk2; however, the levels of Cdc25C phosphorylation were decreased in response to glutamine deprivation in a time-dependent manner. Our data provide a first biochemical evidence that glutamine deprivation suppresses cell viability through G2/M phase arrest without induction of apoptosis in PC3 cells.

• Journal of Korean Medicine Rehabilitation
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• v.19 no.2
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• pp.103-112
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• 2009

Objectives : This study was to evaluate the pharmacological effect of Korea Red Ginseng aqueous extract (KRGE) on serum-deprived apoptosis of neuronal-like pheochromocytoma PC12 cells and to investigate its underlying action mechanism. Methods : KRGE was prepared by extracting Korea Red Ginseng with hot water and concentrating using a vacuum evaporator. Cell viability was determined after incubation of cells with KRGE or chemical inhibitor in serum-deprived medium for 60 h by counting intact nuclei following lysing of the cell membrane. Caspase activities were measured using chromogenic substrates and signal-associated protein phosphorylation and cytochrome c release were determined by Western blot analyses using their specific antibodies. Results : Serum deprivation induced PC12 cell death, which was accompanied by typical morphological features of apoptotic cell, such as nuclear fragmentation, caspase-3 activation, and cytochrome c release. This apoptotic cell death was significantly inhibited by KRGE and caspase-3 inhibitor, but not by the addition of NMA, ODQ, and PD98059. KRGE promoted phosphorylation of Akt and Bad, and this phosphorylation was inhibited by the PI3K inhibitor LY92004. In addition, this inhibitor also reversed KRGE-mediated protection of PC 12 cells from serum deprivation. These results suggested that KRGE protects PC12 cells from serum deprivation-induced apoptosis through the activation of PI3K/Akt-dependent Bad phosphorylation and cytochrome c release, resulting in caspase-3 activation. Conclusions : KRGE should be considered as a potential therapeutic drug for brain diseases including stroke induced by apoptosis of neuronal cells.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6369-6374
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• 2012

Vitexicarpin (3', 5-dihydroxy-3, 4', 6, 7-tetramethoxyflavone), a polymethoxyflavone isolated from Viticis Fructus (Vitex rotundifolia Linne fil.), has long been used as an anti-inflammatory herb in traditional Chinese medicine. It has also been reported that vitexicarpin can inhibit the growth of various cancer cells. However, there is no report elucidating its effect on human prostate carcinoma cells. The aim of the present study was to examine the apoptotic induction activity of vitexicarpin on PC-3 cells and molecular mechanisms involved. MTT studies showed that vitexicarpin dose-dependently inhibited growth of PC-3 cells with an $IC_{50}{\sim}28.8{\mu}M$. Hoechst 33258 staining further revealed that vitexicarpin induced apoptotic cell death. The effect of vitexicarpin on PC-3 cells apoptosis was tested using prodium iodide (PI)/Annexin V-FITC double staining and flow cytometry. The results indicated that vitexicarpin induction of apoptotic cell death in PC-3 cells was accompanied by cell cycle arrest in the G2/M phase. Furthermore, our study demonstrated that vitexicarpin induction of PC-3 cell apoptosis was associated with upregulation of the proapoptotic protein Bax, and downregulation of antiapoptotic protein Bcl-2, release of Cytochrome c from mitochondria and decrease in mitochondrial membrane potential. Our findings suggested that vitexicarpin may become a potential leading drug in the therapy of prostate carcinoma.

• Journal of Life Science
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• v.20 no.7
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• pp.991-998
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• 2010

Hypoxia is an indicative of pro-apoptotic and anti-apoptotic biphasic effects, which appear to be dependent upon the cell type and the condition of the cells. The hypoxia-mimetic agent, cobalt chloride ($CoCl_2$), has been shown to induce apoptosis in a variety of cell types, but the mechanism by which this occurs has yet to be thoroughly elucidated. Puromycin-sensitive aminopeptidase (PSA) gene was decreasingly expressed in response to $CoCl_2$. In this report, puromycin pretreatment applied to PC-3 cells resulted in apoptosis. To determine whether PSA is involved in apoptosis, we examined the apoptotic properties of the PC-3 cells after siRNA knockdown of PSA. PSA siRNA-induced PSA silencing revealed that endogenous PSA may be involved in apoptosis of the PC-3 cells. These results indicated that PSA may perform a vital function in cell survival of the PC-3 cells.

• Nutrition Research and Practice
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• v.1 no.3
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• pp.195-199
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• 2007

Inositol hexaphosphate ($IP_6$) is a major constituent of most cereals, legumes, nuts, oil seeds and soybean. Previous studies reported the anticancer effect of $IP_6$ and suggested that co-treatment of $IP_6$ with inositol may enhance anticancer effect of $IP_6$. Although the anticancer effect of $IP_6$ has been intensively studied, the combinational effect of $IP_6$ and inositol and involved mechanisms are not well understood so far. In the present study, we investigated the effect of $IP_6$ and myo-inositol (MI) on cell cycle regulation and apoptosis using PC3 prostate cancer cell lines. When cell, were co-treated with $IP_6$ and MI, the extent of cell growth inhibition was significantly increased than that by $IP_6$ alone. To identify the effect of $IP_6$ and MI on apoptosis, the activity of caspase-3 was measured. The caspase-3 activity was significantly increased when cells were treated with either $IP_6$ alone or both $IP_6$ and MI, with no significant enhancement by co-treatment. To investigate the effect of $IP_6$ and MI of cell cycle arrest, we measured p21 mRNA expression in PC3 cells and observed significant increase in p21 mRNA by $IP_6$. But synergistic regulation by co-treatment with $IP_6$ and MI was not observed. In addition, there was no significant effect by co-treatment compared to $IP_6$ treatment on the regulation of cell cycle progression although $IP_6$ significantly changed cell cycle distribution in the presence of MI or not. Therefore, these findings support that $IP_6$ has anticancer function by induction of apoptosis and regulation of cell cycle. However, synergistic effect by MI on cell cycle regulation and apoptosis was not observed in PC3 prostate cancer cells.

• Journal of Acupuncture Research
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• v.24 no.2
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• pp.15-29
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• 2007

목적 : 후박(厚朴)(Magnolia Obovata)에서 추출한 낮은 농도의 Obovatol 약침액의 RAW264.7 세포에서 LPS로 유발된 염증，$TNF-{\alpha}$로 유발된 human Prostate carcinoma PC-3 및 LNCap 세포의 세포증식에 대한 영향과 그 기전을 살펴보고자 하였다. 방법 : RAW264.7 세포에서 LPS로 염증을 유발하고 낮은 농도의 Obovatol 약침액을 처리한 후 cell viability, NO 생성량，iNOS와 COX-2의 발현, $NF-{\kappa}B$활성，전사능력을 관찰하기 위해 MTT assay, NO determination assay, western blot analysis, EMSA, luciferase activity assay를 시행하였고，LNCap, PC-3 세포에 $TNF-{\alpha}$로 증식을 유도하고 낮은 농도의 Obovatol 약침액을 처리한 후 cell growth, apoptosis 및 apoptosis와 연관된 $NF-{\kappa}B$의 활성 변화를 관찰하기 위해 WST-1, Cell morphogy test, DAPI staining and TUNEL assay, EMSA, luciferase activity assay를 시행하였다. 결과 : 1. RAW264.7 세포에서 낮은 농도의 Obovatol 약침액 처리는 $NF-{\kappa}B$의 활성 및 전사능력을 낮추고 iNOS와 COX-2의 발현과 NO 생성을 감소시켜 LPS로 유발된 염증을 억제하였다. 2. LNCap, PC-3 세포에서 낮은 농도의 Obovatol 약침액 처리는 $NF-{\kappa}B$의 활성을 낮추어 세포자별사를 촉진함으로써 $TNF-{\alpha}$로 유발된 암세포의 성장을 억제하였다. 결론 : 이상의 결과는 낮은 농도의 Obovatol 약침액이 항염 및 인간 전립선암세포주인 PC-3, LNCap에 대한 증식억제 효과가 있음을 입증한 것이며，향후 이를 바탕으로한 생체 연구에서의 긍정적인 결과는 Obovatol 약침액이 만성염증성 질환 및 전립선암의 예방과 치료에 대한 효과적인 치료제 개발에 초석이 될 것으로 기대된다.

• Toxicological Research
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• v.14 no.3
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• pp.341-348
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• 1998

We established an in vitro experimental system using the following procedure. We first introduced tritium-labelled norepinephrine ([3H]-NE)into PC12 cells. The [3H]-NE incorporated into PC12 cells were then stimulated by a high concentration (60 mM) of $K^+$ during 12 minutes. Then, we counted the amount of [3H]-NE release from PC12 cells with the scintillation counter. After screening fungal, Streptomyces or bacterial product using this experimental system, we obtained S9940 from Streptomyces spp. which inhibited [3H]-NE release from PC12 cells. S9940 also inhibits the release of ATP as a neurotransmitter of PC12 cells and rat cortical neurons. The inhibitory effect was seen even when the PC12 cells were treated with low $K^+$ buffer containing ionomycin $(1\muM)$ as an ionopore. This result suggests that the inhibitory action of S9940 on neurotransmitter release appeared after the influx of $Ca^{2+}$.