• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.399-402
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• 2012

Bufalin is a traditional oriental medicines which induces apoptosis in some lines of human tumor cells. It constitutes the major digoxin-like immunoreactive component of Chan Su, obtained from the skin and parotid venom glands of toads. Bufalin is cardioactive C-24 steroids that exhibits a variety of biological activities, such as cardiotonic, anaesthetic, blood pressure stimulatory, respiratory and antineoplastic effects. In terms of its anti-tumor activity, bufalin has been demonstrated to inhibit the growth of tumors, such as endometrial and ovarian cancers. This commentary introduces biologic and therapeutic effects of bufalin in treating some cancers. The compound is able to mediate inhibition of cell growth, cell cycle arrest, apoptosis, and expression of genes related to the malignant phenotype in human cancer cells.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.765-768
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• 2013

Background and Aims: Prostate cancer is the most commonly diagnosed cancer in males in many populations. Metformin is the most widely used anti-diabetic drug in the world, and there is increasing evidence of a potential efficacy of this agent as an anti-cancer drug. Metformin inhibits the proliferation of a range of cancer cells including prostate, colon, breast, ovarian, and glioma lines. MicroRNAs (miRNAs) are a class of small, non-coding, single-stranded RNAs that downregulate gene expression. We aimed to evaluate the effects of metformin treatment on changes in miRNA expression in PC-3 cells, and possible associations with biological behaviour. Materials and Methods: Average cell viability and cytotoxic effects of metformin were investigated at 24 hour intervals for three days using the xCELLigence system. The $IC_{50}$ dose of metformin in the PC-3 cells was found to be 5 mM. RNA samples were used for analysis using custom multi-species microarrays containing 1209 probes covering 1221 human mature microRNAs present in miRBase 16.0 database. Results: Among the human miRNAs investigated by the arrays, 10 miRNAs were up-regulated and 12 miRNAs were down-regulated in the metformin-treated group as compared to the control group. In conclusion, expression changes in miRNAs of miR-146a, miR-100, miR-425, miR-193a-3p and, miR-106b in metformin-treated cells may be important. This study may emphasize a new role of metformin on the regulation of miRNAs in prostate cancer.

• Korean Journal of Clinical Laboratory Science
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• v.47 no.4
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• pp.298-305
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• 2015

Stem cell-like tumor cells are reported to be the main reason for tumor recurrence and metastasis. As one of the new approaches to overcome cancer, studies are emerging to inhibit the expressions of stem cell transcriptional factors (Oct4, Sox2, Klf-4, and Lin28) in cancer cells. MicroRNAs are master genetic regulators that can control development and differentiation of stem cells. In this study using various ovarian tumors (Skov3, Ovcar3, Tov112D, Tov21G, PA-1 and Hsc832(c)T), we examined the expressions of stem cell-related transcription factors, and the biological changes in cell survival and growth by miR-126 that targets stem cell transcriptional factors. We observed that treatment of miR-126 induced the morphological changes and cell suspension in most cells. In addition, miR-126 induced gradual regression of cell division except Skov3 cells, especially significant time-dependent reduction in Tov112D, Tov21G and PA-1. When we examined the expression of stem cell transcriptional factors, Sox2 was shown to be down-regulated after miR-126. Our results demonstrate that miR-126 treatment can provide the reversible environment to regulate cell division and to induce cell death of ovarian tumors, suggesting the molecular biological clues for clinical usage.

• Biomolecules & Therapeutics
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• v.30 no.3
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• pp.265-273
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• 2022

Resistance to chemotherapeutic drugs is a significant problem in the treatment of colorectal cancer, resulting in low response rates and decreased survival. Recent studies have shown that shikonin, a naphthoquinone derivative, promotes apoptosis in colon cancer cells and cisplatin-resistant ovarian cells, raising the possibility that this compound may be effective in drug-resistant colorectal cancer. The aim of this study was to characterize the molecular mechanisms underpinning shikonin-induced apoptosis, with a focus on endoplasmic reticulum (ER) stress, in a 5-fluorouracil-resistant colorectal cancer cell line, SNU-C5/5-FUR. Our results showed that shikonin significantly increased the proportion of sub-G₁ cells and DNA fragmentation and that shikonin-induced apoptosis is mediated by mitochondrial Ca²⁺ accumulation. Shikonin treatment also increased the expression of ER-related proteins, such as glucose regulatory protein 78 (GRP78), phospho-protein kinase RNA-like ER kinase (PERK), phospho-eukaryotic initiation factor 2 (eIF2α), phospho-phosphoinositol-requiring protein-1 (IRE1), spliced X-box-binding protein-1 (XBP-1), cleaved caspase-12, and C/EBP-homologous protein (CHOP). In addition, siRNA-mediated knockdown of CHOP attenuated shikonin-induced apoptosis, as did the ER stress inhibitor TUDCA. These data suggest that ER stress is a key factor mediating the cytotoxic effect of shikonin in SNU-C5/5-FUR cells. Our findings provide an evidence for a mechanism in which ER stress leads to apoptosis in shikonin-treated SNU-C5/5-FUR cells. Our study provides evidence to support further investigations on shikonin as a therapeutic option for 5-fluorouracil-resistant colorectal cancer.

• Journal of Microbiology and Biotechnology
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• v.32 no.4
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• pp.493-503
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• 2022

Forkhead transcription factor 3a (Foxo3a) is believed to be a tumor suppressor as its inactivation leads to cell transformation and tumor development. However, further investigation is required regarding the involvement of the activating transcription factor 3 (ATF3)-mediated Tat-interactive protein 60 (Tip60)/Foxo3a pathway in cancer cell apoptosis. This study demonstrated that Chelidonium majus upregulated the expression of ATF3 and Tip60 and promoted Foxo3a nuclear translocation, ultimately increasing the level of Bcl-2-associated X protein (Bax) protein. ATF3 overexpression stimulated Tip60 expression, while ATF3 inhibition by siRNA repressed Tip60 expression. Furthermore, siRNA-mediated Tip60 inhibition significantly promoted Foxo3a phosphorylation, leading to blockade of Foxo3a translocation into the nucleus. Thus, we were able to deduce that ATF3 mediates the regulation of Foxo3a by Tip60. Moreover, siRNA-mediated Foxo3a inhibition suppressed the expression of Bax and subsequent apoptosis. Taken together, our data demonstrate that Chelidonium majus induces SKOV-3 cell death by increasing ATF3 levels and its downstream proteins Tip60 and Foxo3a. This suggests a potential therapeutic role of Chelidonium majus against ovarian cancer.

• Journal of Life Science
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• v.21 no.7
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• pp.923-931
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• 2011

In the present study, we investigated the effect of indole-3-carbinol (I3C), a natural compound present in vegetables, on the cell migration and invasion of OVCAR-3 ovarian cancer cells. Our results indicated that I3C inhibited the proliferation of OVCAR-3 cells, a process which was associated with inhibition of cell motility as determined by wound healing experiments and cell invasion studies. I3C treatment increased the tightness of the tight junctions (TJs), which was demonstrated by an increase in transepithelial electrical resistance and a decrease in paracellular permeability. The RT-PCR and immunoblotting results indicated that I3C repressed the levels of claudin-3 as well as claudin-4, proteins that comprise a major part of TJs and play a key role in the control and selectivity of paracellular transport. Furthermore, the activities of matrix metalloproteinase (MMP)-2 and MMP-9 were also decreased by treatment with I3C, which was connected with the down-regulation of their mRNAs and protein expression. The results suggest that I3C may be expected to inhibit cancer cell metastasis and invasion by restoring TJs and decreasing MMP activity in ovarian cancer cell line OVCAR-3.

• Toxicological Research
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• v.27 no.4
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• pp.253-259
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• 2011

Transforming growth factor ${\beta}$ (TGF-${\beta}$) is involved in cellular processes including growth, differentiation, apoptosis, migration, and homeostasis. Generally, TGF-${\beta}$ is the inhibitor of cell cycle progression and plays a role in enhancing the antagonistic effects of many growth factors. Unlike the antiproliferative effect of TGF-${\beta}$, E2, an endogeneous estrogen, is stimulating cell proliferation in the estrogen-dependent organs, which are mediated via the estrogen receptors, $ER{\alpha}$ and $ER{\beta}$, and may be considered as a critical risk factor in tumorigenesis of hormone-responsive cancers. Previous researches reported the cross-talk between estrogen/$ER{\alpha}$ and TGF-${\beta}$ pathway. Especially, based on the E2-mediated inhibition of TGF-${\beta}$ signaling, we examined the inhibition effect of 4-tert-octylphenol (OP) and 4-nonylphenol (NP), which are well known xenoestrogens in endocrine disrupting chemicals (EDCs), on TGF-${\beta}$ signaling via semi-quantitative reverse-transcription PCR. The treatment of E2, OP, or NP resulted in the downregulation of TGF-${\beta}$ receptor2 (TGF-${\beta}$ R2) in TGF-${\beta}$ signaling pathway. However, the expression level of TGF-${\beta}1$ and TGF-${\beta}$ receptor1 (TGF-${\beta}$ R1) genes was not altered. On the other hand, E2, OP, or NP upregulated the expression of a cell-cycle regulating gene, c-myc, which is a oncogene and a downstream target gene of TGF-${\beta}$ signaling pathway. As a result of downregulation of TGF-${\beta}$ R2 and the upregulation of c-myc, E2, OP, or NP increased cell proliferation of BG-1 ovarian cancer cells. Taken together, these results suggest that E2 and these two EDCs may mediate cancer cell proliferation by inhibiting TGF-${\beta}$ signaling via the downregulation of TGF-${\beta}$ R2 and the upregulation of c-myc oncogene. In addition, it can be inferred that these EDCs have the possibility of tumorigenesis in estrogen-responsive organs by certainly representing estrogenic effect in inhibiting TGF-${\beta}$ signaling.

• Journal of the Korean Society of Visualization
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• v.18 no.3
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• pp.84-89
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• 2020

Cancer cells secrete angiogenic factors, and nearby vasculatures make new blood vessels essential for cancer development and metastasis in response to these soluble factors. Many efforts have been made to elucidate cancer-endothelial cell interactions in vitro. However, not much is known due to the lack of a suitable co-culture platform. Here, we introduce a 3D printing-based microfluidic system that mimics the in vivo-like cancer-endothelial cell interactions. The tumoroids and endothelial cells are co-cultured, physically separated by porous fibrin gel, allowing communication between two cell types through soluble factors. Using this microfluidic system, we were able to visualize new vessel formation induced by tumoroids of different origins, including liver, breast, and ovary. We confirmed that the ovarian tumoroids most induced angiogenesis while the other two cancer types suppressed it. Utilization of the proposed co-culture platform will help the researchers unveil the underlying mechanisms of the dynamic interplay between tumor and angiogenesis.

• Journal of Microbiology and Biotechnology
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• v.13 no.4
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• pp.517-521
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• 2003

Telomerase is a ribonucleoprotein complex whose function is to add telomeric repeats to chromosomal ends. Telomerase consists of two essential components, telomerase RNA template (hTR) and catalytic subunit (hTERT). hTERT is expressed only in cells and tissues positive for telomerase activity, i.e., tumor and fetal cells. In this report, the possibility of utilization of the hTERT promoter in targeted cancer gene therapy was tested. The hTERT promoter was cloned in the replacement of the CMV promoter, and the HSV-TK gene was subcloned to be controlled by the hTERT gene promoter in the adenovirus shuttle plasmid. Then, the recombinant adenovirus Ad-hT-TK was constructed and was infected into normal and human gynecological cancer cell lines. The selective tumor specific cell death by Ad-hT-TK was identified through these experiments, showing that Ad-hT-TK could be used for targeted cancer gene therapy.

• BMB Reports
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• v.56 no.3
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• pp.184-189
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• 2023

Ovarian cancer (OC) is the most common gynecological malignancy worldwide, and chemoresistance occurs in most patients, resulting in treatment failure. A better understanding of the molecular processes underlying drug resistance is crucial for development of efficient therapies to improve OC patient outcomes. Circular RNAs (circRNAs) and ferroptosis play crucial roles in tumorigenesis and resistance to chemotherapy. However, little is known about the role(s) of circRNAs in regulating ferroptosis in OC. To gain insights into cisplatin resistance in OC, we studied the ferroptosis-associated circRNA circSnx12. We evaluated circSnx12 expression in OC cell lines and tissues that were susceptible or resistant to cisplatin using quantitative real-time PCR. We also conducted in vitro and in vivo assays examining the function and mechanism of lnc-LBCSs. Knockdown of circSnx12 rendered cisplatin-resistant OC cells more sensitive to cisplatin in vitro and in vivo by activating ferroptosis, which was at least partially abolished by downregulation of miR-194-5p. Molecular mechanics studies indicate that circSnx12 can be a molecular sponge of miR-194-5p, which targets SLC7A11. According to our findings, circSnx12 ameliorates cisplatin resistance by blocking ferroptosis via a miR-194-5p/SLC7A11 pathway. CircARNT2 may thus serve as an effective therapeutic target for overcoming cisplatin resistance in OC.