• Fisheries and Aquatic Sciences
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• 제24권1호
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• pp.1-9
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• 2021

Human prostate cancer is the second most frequently diagnosed cancer worldwide, and its incidence rate continues to increase. Advanced prostate cancer is more difficult to treat than early forms due to its chemotherapy resistance. There is need for more effective agents that can inhibit the progression of advanced prostate cancer. Demethoxyfumitremorgin C (DMFTC) was isolated from the fermentation extract of the marine fungus Aspergillus fumigatus. Antiproliferative activity of DMFTC against human prostate cancer PC3 cells was examined through cell cycle analysis by flow cytometry, the fluorescent nuclear imaging analysis with propidium iodide (PI), and proteins expression related to cell cycle arrest and apoptosis were investigated via Western blotting. DMFTC inhibited PC3 cells growth through G1 phase cell cycle arrest and apoptosis induction. It activated the tumor suppressor p53 and the Cdk inhibitor p21, which regulate the cell progression into the G1 phase. Additionally, PI-positive late apoptotic non-viable cells were increased and the expression levels of the G1-positive downstream regulators cyclin D, cyclin E, Cdk2, and Cdk4 were decreased by DMFTC treatment. These results suggest that DMFTC induces G1 arrest and apoptosis induction through regulation of p53/p21-dependent cyclin-Cdk complexes, and it may be a useful therapeutic agent for the treatment of human advanced prostate cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1423-1428
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• 2014

Iso-suillin, a natural product isolated from Suillus luteus, has been shown to inhibit the growth of some cancer cell lines. However, the molecular mechanisms of action of this compound are poorly understood. The purpose of this study was to investigate how iso-suillin inhibits proliferation and induces apoptosis in a human hepatoma cell line (SMMC-7721). We demonstrated the effects of iso-suillin on cell proliferation and apoptosis in SMMC-7721 cells, with no apparent toxicity in normal human lymphocytes, using colony formation assays and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis. Western blotting was used to examine the expression of $G_1$ phase-regulated and apoptosis-associated protein levels in iso-suillin treated SMMC-7721 cells. The results indicated that iso-suillin significantly decreased viability, induced $G_1$ phase arrest and triggered apoptosis in SMMC-7721cells. Taken together, these results suggest the potential of iso-suillin as a candidate for liver cancer treatment.

• 약학회지
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• 제55권5호
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• pp.391-397
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• 2011

KML001 reduced the proliferation of HCT116 cells in a concentration- and time-dependent manner without change of cell viability. Beclin-1 expression was significantly attenuated by KML001 (P<0.05), but no significant changes were observed in KML001-treated cells. The number of cells in G1 phase was increased 48 hr after KML001 treatment. Furthermore, a dramatic reduction in the frequency of beating and the number of embryoid bodies of the cells was noted after treatment. Taken together, KML001 suppresses the proliferation of HCT116 cells, which might be due to G1 phase arrest.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.1655-1659
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• 2016

Celecoxib, a selective inhibitor of COX-2, showed cytotoxic effects in many cancer cell lines including cervical cancer cells. This study investigated the effect of celecoxib on cell cycle arrest in HeLa cervical cancer cells through p53 expression. In vitro anticancer activity was determined with the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) method. A double staining method was applied to investigate the mechanism of cell death, cell cycling was analyzed by flow cytometryand immunocytochemistry was employed to stain p53 expression in cells. Celecoxib showed strong cytotoxic effects and induced apoptosis with an $IC_{50}$ value of $40{\mu}M$. It induced cell cycle arrest at G2/M phase by increasing level of p53 expression on HeLa cells.

• Journal of Pharmaceutical Investigation
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• 제35권5호
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• pp.361-367
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• 2005

In this study, we evaluated and compared the pharmacodynamics of paclitaxel (PTX) in human A549 NSCLC cells grown as monolayers or as three-dimensional histocultures. Growth inhibitory effects were determined after incubating cells in drug free medium until 96 hr post drug exposure initiation. Cell cycle arrest and apoptosis were measured by flow cytometry. The growth inhibition induced by PTX was significantly different in monolayers and histocultures, and PTX showed significantly less cytotoxicity in histocultures where large resistant fractions were observed. Moreover, although PIX induced significant $G_{2}/M$ arrest followed by apoptosis in monolayers in a drug concentration-dependant manner, $G_{2}/M$ arrest was not elicited in histocultures. However, apoptotic cells appeared from the $G_{2}/M$ phase in histocultures. In this study, we provide first evidence that PIX in three-dimensional histocultures, does not induce $G_{2}/M$ arrest, but rather that it induces $G_{2}/M$ phase specific apoptosis. Overall, our data demonstrate different pharmacodynamics of PTX in traditional monolayer and three-dimensional histocultures.

• 한방안이비인후피부과학회지
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• 제32권4호
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• pp.1-12
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• 2019

Objectives : The purpose of this study was to identify the anticancer effect of biological substances of ethylacetate(EtOAc) fraction from Orostachys japonicus(OJEF), their effect on human melanoma A375 cells and the related molecular mechanisms. Methods : The MTS assay was used to confirm the inhibition of cancer cell proliferation in A375 cells. And the $MUSE^{TM}$ analyzer was used to determine the ability of OJEF to induce cell cycle arrest. Western blotting was used to determine the changes in protein expression in A375 cells after treatment with OJEF. Results : OJEF showed cytotoxicity to A375 cells. And cell cycle arrest occurred in G1 phase and G2/M phase owing to inhibition of CDK1, cyclin B1, CDK4, and cyclin D, which are related to cell cycle regulation and cell division control. Conclusion : OJEF is effective in regulating cell cycle of human melanoma cells and thus can be a good theraputic agent to treat patients with melanoma.

• Toxicological Research
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• 제21권1호
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• pp.77-85
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• 2005

Cadmium is an environmental pollutant exposed from contaminated foods or cigarette smoking and known to cause oxidative damage in organs. We investigated the cadmium-induced apoptosis and cell arrest in human breast cancer cells, MCF-7 cells and MDA-MB-231 cells. Obvious apoptotic cell death was shown in CdCl₂ 100 μM treatment for 12 hr, which were determined by DAPI staining and flow cytometric analysis. In cell cycle analysis, MCF-7 cells and MDA-MB-231 cells were arrested in S phase and G2/M phase respectively. These could be explained by the induction of cell cycle inhibitory protein, p21/sup Waf1/Cip1/ and p27/sup Kip1/, expression and reduction of cyclin/Cdk complexes in both cell lines. The decreased expression of cyclin A and Cdk2 in MCF-7 cells and cyclin B1 and Cdc2 in MDA-MB-231 cells were consistent with the flow cytometric observation. p-ERK expression was increased dose-dependent manner in both cell lines. It suggests that ERK MAPK pathway are involved in cadmium-induced cell cycle arrest and apoptosis. Moreover, cotreatment of zinc (100 μM, 12 hr) recovered the cadmium-induced cell arrest in both cells, which shows cadmium-induced oxidative stress mediates apoptosis and cell cycle arrest in human breast cancer cells.

• 동의생리병리학회지
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• 제27권1호
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• pp.43-48
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• 2013

Cisplatin is a anti-neoplastic agent which is commonly used for the treatment of solid tumor. Cisplatin activates multiple signal transduction pathways involved in the stress-induced apoptosis in a variety of cell types. Previous study reported that cisplatin induces apoptosis through activation of ERK, p38 and JNK in rat mesangial cells, but apoptotic pathway remain known. The present study investigated the apoptotic pathway for cisplatin-indcued apoptosis in rat mesangial cells. cisplatin-induced apoptosis was associated with activation of caspase-3, caspase-8, caspase-9. Caspase-8 inhibition prevented the activation of both caspase-3 and caspase-9. In addition, cisplatin-induced apoptosis increased the expression of Bax, but not the level of Bcl-2. These change of Bax/bcl-2 ratio caused the release of cytochrome c from mitochondria into cytosol. In previous study, the ethanol extract of Bojungbangam-tang (EBJT) inhibited cisplatin-induced apoptosis in rat mesangial cells through inhibition of ERK and JNK activation. However, EBJT did not increase cell proliferation, because it did not prevent cisplatin-induced G2/M phase arrest. These effect of EBJT may be related to p38 activation. Cisplatin-induced G2/M phase arrest are inhibited by treatment with p38 inhibitor and EBJT in rat mesangial cells. Also, p38 inhibition and EBJT treatment on cisplatin-induced G2/M phase arrest are markedly increased the G0/G1 phase and reduced the sub-G1. In conclusion, anti-apoptotic effet of EBJT did not increases cell proliferation, because EBJT did not reduce p38 activation related to cisplatin-induced G2/M phase arrest.

• Asian Pacific Journal of Cancer Prevention
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• 제16권18호
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• pp.8313-8319
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• 2016

We have recently shown that thymoquinone (TQ) has a potent cytotoxic effect and induces apoptosis via caspase-3 activation with down-regulation of XIAP in mouse neuroblastoma (Neuro-2a) cells. Interestingly, our results showed that TQ was significantly more cytotoxic towards Neuro-2a cells when compared with primary normal neuronal cells. In this study, the effects of TQ on cell-cycle regulation and the mechanisms that contribute to this effect were investigated using Neuro-2a cells. Cell-cycle analysis performed by flow cytometry revealed cell-cycle arrest at G2/M phase and a significant increase in the accumulation of TQ-treated cells at sub-G1 phase, indicating induction of apoptosis by the compound. Moreover, TQ increased the expression of p53, p21 mRNA and protein levels, whereas it decreased the protein expression of PCNA, cyclin B1 and Cdc2 in a dose-dependent manner. Our finding suggests that TQ could suppress cell growth and cell survival via arresting the cell-cycle in the G2/M phase and inducing apoptosis of neuroblastoma cells.

• 생명과학회지
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• 제26권9호
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• pp.1015-1021
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• 2016

Pyrimidine 유도체의 일종인 5-fluorouracil (5-FU)은 광범위하게 사용되는 항암제의 일종으로, thymidylate synthase의 활성을 억제시켜 핵산의 합성 및 대사기능 자애 유발 물질이다. 본 연구에서는 Ewing′s 육종 CHP-100 세포에서 5-FU의 증식억제와 연관된 기전 해석으로 시도하였다. 본 연구의 결과에 의하면, 5-FU 처리 시간의 경과에 따른 CHP-100 세포의 증식억제가 세포주기 G1 arrest 유발에 따른 것임을 알 수 있었다. 5-FU에 의한 CHP-100 세포의 G1 arrest는 retinoblastoma protein (pRB)의 탈인산화에 따른 전사인자 E2F-1 및 E2F-4와의 결합 촉진과 연관성이 있었다. 비록 5-FU 처리가 cyclin-dependent kinases의 발현에는 크게 영향을 주지 않았으나, 정상배지에서 배양된 대조군에 비하여 cyclin A 및 B의 발현이 5-FU 처리 시간 의존적으로 억제되었다. 또한 5-FU에 의한 CHP-100 세포의 G1 arrest는 apoptosis 유도와 연관이 있음을 핵 내 염색질의 응축에 따른 apoptotic body의 형성증가, poly (ADP-ribose) polymerase의 단편화 및 annexin V 염색 등을 통하여 확인하였다. 아울러 5-FU는 pro-apoptotic Bax 단백질의 발현 증가 및 anti-apoptotic Bcl-2의 발현 감소를 통한 mitochondrial membrane potential의 소실을 촉진시켰으며, 이로 인하여 미토콘드리아에서 세포질로의 cytochrome c 유리가 증가시켰음을 알 수 있었다. 따라서 본 연구의 결과는 5-FU에 의한 CHP-100 세포의 증식억제와 연관된 G1 arrest 및 apoptosis 유도에는 pRB의 인산화 억제 및 미토콘드리아 기능의 손상이 최소한 관여하고 있음을 의미하는 것이다.