• BMB Reports
• /
• 제54권7호
• /
• pp.335-343
• /
• 2021

Cancer stem cells (CSCs) are a subpopulation of cancer that can self-renew and differentiate into large tumor masses. Evidence accumulated to date shows that CSCs affect tumor proliferation, recurrence, and resistance to chemotherapy. Recent studies have shown that, like stem cells, CSCs maintain cells with self-renewal capacity by means of asymmetric division and promote cell proliferation by means of symmetric division. This cell division is regulated by fate determinants, such as the NUMB protein, which recently has also been confirmed as a tumor suppressor. Loss of NUMB expression leads to uncontrolled proliferation and amplification of the CSC pool, which promotes the Notch signaling pathway and reduces the expression of the p53 protein. NUMB genes are alternatively spliced to produce six functionally distinct isoforms. An interesting recent discovery is that the protein NUMB isoform produced by alternative splicing of NUMB plays an important role in promoting carcinogenesis. In this review, we summarize the known functions of NUMB and NUMB isoforms related to the proliferation and generation of CSCs.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권9호
• /
• pp.5513-5518
• /
• 2013

IFN-${\gamma}$ plays an indirect anti-cancer role through the immune system but may have direct negative effects on cancer cells. It regulates the viability of gastric cancer cells, so we examined whether it affects their proliferation and how that might be brought about. We exposed AGS, HGC-27 and GES-1 gastric cancer cell lines to IFN-${\gamma}$ and found significantly reduced colony formation ability. Flow cytometry revealed no effect of IFN-${\gamma}$ on apoptosis of cell lines and no effect on cell aging as assessed by ${\beta}$-gal staining. Microarray assay revealed that IFN-${\gamma}$ changed the mRNA expression of genes related to the cell cycle and cell proliferation and migration, as well as chemokines and chemokine receptors, and immunity-related genes. Finally, flow cytometry revealed that IFN-${\gamma}$ arrested the cells in the G1/S phase. IFN-${\gamma}$ may slow proliferation of some gastric cancer cells by affecting the cell cycle to play a negative role in the development of gastric cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권3호
• /
• pp.1241-1245
• /
• 2014

Cinobufacin is used clinically to treat patients with many solid malignant tumors. However, the mechanisms underlying action remain to be detailed. Our study focused on miRNAs involved in cinobufacin inhibition of GC cell proliferation. miRNA microarray analysis and real time PCR identified miR-494 as a significant cinobufacin-associated miRNA. In vivo, ectopic expression of miR-494 inhibited the proliferation and induced apoptosis of BGC-823 cells on CCK-8 and flow cytometry analysis. Further study verified BAG-1 (anti-apoptosis gene) to bea target of miR-494 by luciferase reporter assay and Western blotting. In summary, our study demonstrated that cinobufacin may inhibit the proliferation and promote the apoptosis of BGC-823 cells. Cinobufacin-associated miR-494 may indirectly be involved in cell proliferation and apoptosis by targeting BAG-1, pointing to use as a potential molecular target of cinobufacin in gastric cancer therapy.

• BMB Reports
• /
• 제46권1호
• /
• pp.25-30
• /
• 2013

Gap junctions and their structural proteins, connexins (Cxs), have been implicated in carcinogenesis. To explore the involvement of Cx32 in gastric carcinogenesis, immunochemical analysis of Cx32 and proliferation marker Ki67 using tissue-microarrayed human gastric cancer and normal tissues was performed. In addition, after Cx32 overexpression in the human gastric cancer cell line AGS, cell proliferation, cell cycle analyses, and $p21^{Cip1}$ and $p27^{Kip1}$ expression levels were examined by bromodeoxyuridine assay, flow cytometry, real-time RT-PCR, and western blotting. Immunohistochemical study noted a strong inverse correlation between Cx32 and Ki67 expression pattern as well as their location. In vitro, overexpression of Cx32 in AGS cells inhibited cell proliferation significantly. $G^1$ arrest, up-regulation of cell cycle-regulatory proteins $p21^{Cip1}$ and $p27^{Kip1}$ was also found at both mRNA and protein levels. Taken together, Cx32 plays some roles in gastric cancer development by inhibiting gastric cancer cell proliferation through cell cycle arrest and cell cycle regulatory proteins.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권8호
• /
• pp.4007-4011
• /
• 2012

Purpose: Retinoblastoma-interacting zinc finger gene (RIZ1) is a tumor suppressor gene which is highly inactivated by promoter hypermethylation in patients with liver fluke-related cholangiocarcinoma (CCA). Epigenetic aberration of this gene might withdraw the ability to restrain tumor cell proliferation and migration. We aimed to define the role of RIZ1 on cell proliferation and migration in CCA cell line. Materials and methods: Small interference RNA (siRNA) was used to knock down the expression of RIZ1 in a CCA-derived cell line in which cell proliferation and cell migration were performed. Results: A predominant nuclear localization of RIZ1 was observed. Reduction of RIZ1 by siRNA augmented cell proliferation and migration. Conclusion: The result suggested that RIZ1 might play a role in regulating cell proliferation and migration in CCA. Reduction of RIZ1 expression may aggravate the progression of CCA.

• 한국식품영양과학회지
• /
• 제36권8호
• /
• pp.983-988
• /
• 2007

본 연구는 녹차의 폴리페놀 성분 중에서 항암효과가 가장 크다고 알려진 EGCG가 인체 유방암 세포 MDA-MB-231의 세포증식억제 기전을 알아보고자 실시하였다. EGCG 처리 농도가 증가할수록 48시간 후에 유방암 세포의 증식이 유의적으로 감소되었다. 세포증식 관련 단백질인 $ErbB_2$, $ErbB_3$, Akt의 단백질 발현은 EGCG의 첨가농도 10 ${\mu}m$ 이상일 때부터 유의적으로 발현이 감소하였고, mRNA 발현은 5 ${\mu}m$ 이상부터 유의적으로 감소되었다. Py20, p-Akt 로 단백질의 인산화를 알아본 결과 EGCG 첨가농도가 증가할수록 $ErbB_2$, $ErbB_3$, Akt 의 인산화가 감소함을 확인할 수 있었다. 본 연구 결과를 종합해 보면 인체 유방암 세포 MDA-MB-231에서 EGCG는 암세포에서 과발현되는 $ErbB_2$, $ErbB_3$, Akt의 세포신호 전달과정 억제를 통하여 암세포의 증식을 억제시키는 것을 알 수 있었다.

• 한방안이비인후피부과학회지
• /
• 제18권1호
• /
• pp.71-81
• /
• 2005

Objective : This Study was to investigate effects of Takli-San on the anti-cancer and proliferation of immunocytes, nitric oxide(NO) production of peritoneal macrophages. Methods : We used Takli-San extract(TLS) with freeze-dried, 8wks-old male mice and cancer cell lines(L120, Sarcoma-180) for this Study. The cytotoxicity and proliferation of cells were tested using a colorimetric tetrazoliun assay(MTT assay). Results : 1. TLS was significantly showed cytotoxicity on the L1210 cell lines. 2. TLS was significantly increased proliferation of thymocytes and splenocytes in vitro. 3. TLS was significantly increased proliferation of thymocytes by all-dosage, but proliferation of splenocytes by low-dosage in normal mice. 4. TLS was significantly increased NO production from peritoneal macrophages in normal mice. 5. TLS was significantly decreased proliferation of L1210 cells in L1210 cells transplanted mice. 6. TLS was significantly increase proliferation of thymocytes by all-dosage, but proliferation of splenocytes by low-dosage in L1210 cells transplanted mice. 7. TLS was significantly increased NO production from peritoneal macrophages in L1210 cells transplanted mice. Conclusions : The present author thought that TLS had action of anti-cancer by becoming immunocytes activity(NO production, proliferation of thymocytes).

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권12호
• /
• pp.6233-6237
• /
• 2012

Survivin, a new member of the inhibitor of apoptosis protein (IAP) family, both inhibits apoptosis and regulates the cell cycle. It is overexpressed in breast tumor tissues. In this study, we designed two survivin specific DNAzymes (DRz1 and DRz2) targeting survivin mRNA. The results showed that DRz1 could decrease the expression of survivin by nearly 60%. Furthermore, DRz1 significantly inhibited cell proliferation, induced apoptosis and inhibited migration in MCF-7 cells. In addition, down-regulation of survivin expression was associated with increased caspase-3 and -9 activities in MCF-7 cells after 24 h transfection. In our experiments, the efficacy of DRz1 to influence survivin levels and associated effects were better than DRz2. Survivin-DRz1 might have anti-tumorigenic activity and may potentially provide the basis for a novel therapeutic intervention in breast cancer treatment.

• 대한의생명과학회지
• /
• 제27권3호
• /
• pp.134-141
• /
• 2021

c-Jun N-terminal kinases (JNKs) have a Janus face, regulating both cell apoptosis and survival. The present study focused on understanding the function of JNK in tumor development and the chemoresistance underlying JNK-mediated cancer cell survival. We identified an inhibitor of JNK1, an important regulator of cancer cell survival. Kinase assay data showed that JNK1-dependent c-Jun phosphorylation was inhibited by indirubin derivatives. In particular, indirubin-3-monoxime (I3M) directly inhibited the phosphorylation of c-Jun in vitro, with a half inhibition dose (IC₅₀) of 10 nM. I3M had a significant inhibitory effect on JNK1 activity. Furthermore, we carried out assays to determine the viability, migration, and proliferation of breast cancer cells. Our results demonstrated that cell growth, scratched wound healing, and colony forming abilities were inhibited by the JNK inhibitor SP600125 and I3M. The combination of SP600125 and I3M significantly decreased cancer cell proliferation, compared with either SP600125 or I3M alone. Our studies may provide further support for JNK1-targeting cancer therapy using the indirubin derivative I3M in breast cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권7호
• /
• pp.3203-3207
• /
• 2012

Backgrounds: To investigate the inhibiting effects of multi-target anti-microRNA antisense oligonucleotide (MTg-AMOs) on proliferation and migration of human gastric cancer cells. Methods: Single anti-microRNA antisense oligonucleotides (AMOs) and MTg-AMOs for miR-221, 21, and 106a were designed and transfected into SGC7901, a gastric cancer cell line, to target the activity of these miRNAs. Their expression was analyzed using stem-loop RT-PCR and effects of MTg-AMOs on human gastric cancer cells were determined using the following two assay methods: CCK8 for cell proliferation and transwells for migration. Results: In the CCK-8 cell proliferation assay, $0.6{\mu}mol/L$ was selected as the preferred concentration of MTg-AMOs and incubation time was 72 hours. Under these experimental conditions, MTg-AMOs demonstrated better suppression of the expression of miR-221, miR-106a, miR-21 in gastric cancer cells than that of single AMOs (P = 0.014, 0.024; 0.038, respectively). Migration activity was also clearly decreased as compared to those in randomized and blank control groups ($28{\pm}4$ Vs $54{\pm}3$, P <0.01; $28{\pm}4$ Vs $59{\pm}4$, P < 0.01). Conclusions: MTg-AMOs can specifically inhibit the expression of multiple miRNAs, and effectively antagonize proliferation and migration of gastric cancer cells promoted by oncomirs.