• Journal of Microbiology and Biotechnology
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• v.33 no.4
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• pp.449-462
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• 2023

Previously, we confirmed that Mychonastes sp. 246 methanolic extract (ME) markedly reduced the viability of BxPC-3 human pancreatic cancer cells. However, the underlying mechanism ME remained unclear. Hence, we attempted to elucidate the anticancer effect of ME on BxPC-3 human pancreatic cancer cells. First, we investigated the components of ME and their cytotoxicity in normal cells. Then, we confirmed the G1 phase arrest mediated growth inhibitory effect of ME using a cell counting assay and cell cycle analysis. Moreover, we found that the migration-inhibitory effect of ME using a Transwell migration assay. Through RNA sequencing, Gene Ontology-based network analysis, and western blotting, we explored the intracellular mechanisms of ME in BxPC-3 cells. ME modulated the intracellular energy metabolism-related pathway by altering the mRNA levels of IGFBP3 and PPARGC1A in BxPC-3 cells and reduced PI3K and mTOR phosphorylation by upregulating IGFBP3 and 4E-BP1 expression. Finally, we verified that ME reduced the growth of three-dimensional (3D) pancreatic cancer spheroids. Our study demonstrates that ME suppresses pancreatic cancer proliferation through the IGFBP3-PI3K-mTOR signaling pathway. This is the first study on the anticancer effect of the ME against pancreatic cancer, suggesting therapeutic possibilities and the underlying mechanism of ME action.

• Biomolecules & Therapeutics
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• v.31 no.1
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• pp.68-72
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• 2023

Pancreatic cancer is one of the most fatal cancers with a poor prognosis. Standard chemotherapies have proven largely ineffective because of their toxicity and the development of resistance. Therefore, there is an urgent need to develop novel therapies. In this study, we investigated the antitumor activity of MS-5, a naphthalene derivative, on BxPC-3, a human pancreatic cancer cell line. We observed that MS-5 was cytotoxic to BxPC-3 cells, as well as inhibited the growth of cells in a concentration- and time- dependent manner. Flow cytometry analysis revealed that the percentage of annexin V-positive cells increased after MS-5 treatment. We also observed cleavage of caspases and poly (ADP-ribose) polymerase, and downregulation of Bcl-xL protein. Flow cytometry analysis of intracellular levels of reactive oxygen species (ROS) and mitochondrial superoxide suggested that MS-5 induced the generation of mitochondrial superoxide while lowering the overall intracellular ROS levels. Thus, MS-5 may be potential candidate for pancreatic cancer treatment.

• YAKHAK HOEJI
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• v.49 no.4
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• pp.335-339
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• 2005

In this study we investigated the effect of 3-methoxy-6-allylthiopyridazine on cell growth in BxPC3 and PANC1 human pancreatic cancer cells. The treatment with 3-methoxy-6-allylthiopyridazine for 48h decreased cell viability and induced apoptotic cell death in a dose-dependent manner, assessed by using the MTT assay and the flow cytometry, respectively. These results suggest that 3-methoxy-6-allylthiopyridazine may be a good candidate for the therapeutic management of human pancreatic cancers.

• Korean Journal of Food Science and Technology
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• v.49 no.2
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• pp.222-227
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• 2017

Red ginseng prepared from fresh 6-year-old ginseng treated with colloidal gold nanoparticles was extracted using hot water to evaluate its total phenolic and flavonoid contents, antioxidant capacity, and neuroprotective effects. Water extract of red ginseng treated with gold nanoparticles (WERGGN) had total phenolic and total flavonoid contents of 212.2 mg gallic acid equivalents/$^{\circ}Bx$ and 3.5 mg catechin equivalents/$^{\circ}Bx$, respectively. The antioxidant capacities of WERGGN measured using ABTS, DPPH, and ORAC assays were 272.3, 141.2, and 868.4 mg vitamin C equivalents/$^{\circ}Bx$, respectively. The WERGGN showed protective effects on the viability of neuron-like PC-12 cells against oxidative stress induced by hydrogen peroxide in a dose-dependent manner, partly because of a reduction in intracellular oxidative stress. Acetylcholinesterase and butyrylcholinesterase, which degrade the neurotransmitter acetylcholine to terminate neurotransmission, were inhibited by treatment with WERGGN. These results suggest that WERGGN is useful as a functional material to decrease oxidative stress and neuronal damage.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.416.3-417
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• 2002

Among the promising cancer therapy is targeting of the drug to tumor cells via receptor specific ligands. CR2945, $\beta$-2-( ［2-(8-azaspiro ［4.5］ dec-8-ylcarbony!)-4.6-dimethylphenyl］amino-2-oxoethyl］ -(R)-1-naphthalenepropanoic acid. is known to have an inhibitory effect on a gastrin receptor of colorectal cancer cells. As the human pancreatic cancer cells (BxPC-3) express gastrin receptors. interruption of binding of gastrin with gastrin receptor of human pancreatic cancer cells by CR2945 inhibits the growth of human pancreatic cancer cells. (omitted)

• Journal of Microbiology and Biotechnology
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• v.32 no.5
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• pp.645-656
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• 2022

Gossypol, a natural phenolic aldehyde present in cotton plants, was originally used as a means of contraception, but is currently being studied for its anti-proliferative and anti-metastatic effects on various cancers. However, the intracellular mechanism of action regarding the effects of gossypol on pancreatic cancer cells remains unclear. Here, we investigated the anti-cancer effects of gossypol on human pancreatic cancer cells (BxPC-3 and MIA PaCa-2). Cell counting kit-8 assays, annexin V/propidium iodide staining assays, and transmission electron microscopy showed that gossypol induced apoptotic cell death and apoptotic body formation in both cell lines. RNA sequencing analysis also showed that gossypol increased the mRNA levels of CCAAT/enhancer-binding protein homologous protein (CHOP) and activating transcription factor 3 (ATF3) in pancreatic cancer cell lines. In addition, gossypol facilitated the cleavage of caspase-3 via protein kinase RNA-like ER kinase (PERK), CHOP, and Bax/Bcl-2 upregulation in both cells, whereas the upregulation of ATF was limited to BxPC-3 cells. Finally, a three-dimensional culture experiment confirmed the successful suppression of cancer cell spheroids via gossypol treatment. Taken together, our data suggest that gossypol may trigger apoptosis in pancreatic cancer cells via the PERK-CHOP signaling pathway. These findings propose a promising therapeutic approach to pancreatic cancer treatment using gossypol.

• Journal of The Korean Astronomical Society
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• v.34 no.4
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• pp.309-311
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• 2001

Strong thermal X-ray emission, called Galactic Ridge X-ray Emission, is observed along the Galactic plane (Koyama et al. 1986). The origin of hot ($\~$7 keV) component of GRXE is not known, while cool ($\~$0.8 keV) one is associated with supernovae (Kaneda et al. 1997, Sugizaki et al. 2001). We propose a possible mechanism to explain the origin; locally strong magnetic fields of $B_{local}\;\~30{\mu}G$ heat interstellar gas to $\~$7 keV via magnetic reconnection (Tanuma et al. 1999). There will be the small-scale (< 10 pc) strong magnetic fields, which can be observed as $(B)_{obs} \;\~3{\mu}G$ by integration of Faraday Rotation Measure, if it is localized by a volume filling factor of f $\~$ 0.1. In order to examine this model, we solved three-dimensional (3D) resistive magnetohydrodynamic (MHD) equations numerically to examine the magnetic reconnect ion triggered by a supernova shock (fig.l). We assume that the magnetic field is Bx = 30tanh(y/20pc) $\mu$G, By = Bz = 0, and the temperature is uniform, at the initial condition. We put a supernova explosion outside the current sheet. The supernova-shock, as a result, triggers the magnetic reconnect ion, and the gas is heatd to > 7 keV. The magnetic reconnect ion heats the interstellar gas to $\~$7 keV in the Galactic plane, if it occurs in the locally strong magnetic fields of $B_{local}\;\~30{\mu}G$. The heated plasma is confined by the magnetic field for $\~10^{5.5} yr$. The required interval of the magnetic reconnect ions (triggered by anything) is $\~$1 - 10 yr. The magnetic reconnect ion will explain the origin of X-rays from the Galactic ridge, furthermore the Galactic halo, and clusters of galaxies.

• Journal of Ginseng Research
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• v.46 no.5
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• pp.636-645
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• 2022

Background: Ginsenoside Rg3 and gemcitabine have mutual enhancing antitumor effects. However, the underlying mechanisms are not clear. This study explored the influence of ginsenoside Rg3 on Zinc finger protein 91 homolog (ZFP91) expression in pancreatic adenocarcinoma (PAAD) and their regulatory mechanisms on gemcitabine sensitivity. Methods: RNA-seq and survival data from The Cancer Genome Atlas (TCGA)-PAAD and Genotype-Tissue Expression (GTEx) were used for in-silicon analysis. PANC-1, BxPC-3, and PANC-1 gemcitabine-resistant (PANC-1/GR) cells were used for in vitro analysis. PANC-1 derived tumor xenograft nude mice model was used to assess the influence of ginsenoside Rg3 and ZFP91 on tumor growth in vivo. Results: Ginsenoside Rg3 reduced ZFP91 expression in PAAD cells in a dose-dependent manner. ZFP91 upregulation was associated with significantly shorter survival of patients with PAAD. ZFP91 overexpression induced gemcitabine resistance, which was partly conquered by ginsenoside Rg3 treatment. ZFP91 depletion sensitized PANC-1/GR cells to gemcitabine treatment. ZFP91 interacted with Testis-Specific Y-Encoded-Like Protein 2 (TSPYL2), induced its poly-ubiquitination, and promoted proteasomal degradation. Ginsenoside Rg3 treatment weakened ZFP91-induced TSPYL2 poly-ubiquitination and degradation. Enforced TSPYL2 expression increased gemcitabine sensitivity of PAAD cells and partly reversed induced gemcitabine resistance in PANC-1/GR cells. Conclusion: Ginsenoside Rg3 can increase gemcitabine sensitivity of pancreatic adenocarcinoma at least via reducing ZFP91 mediated TSPYL2 destabilization.

• Journal of the Korean Physical Society
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• v.73 no.11
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• pp.1619-1624
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• 2018

Laser ablation may provide a minimally invasive palliative treatment for pancreatic cancer. The aim of the current study was to assess the feasibility of a 532-nm laser equipped with a cylindrical light diffuser for the treatment of pancreatic cancer. Monolayers of BxPC-3 human pancreatic cancer cell were exposed to 532 nm laser light. Power levels of 5 - 7 W were used to uniformly target the entire cell colonies for 60 and 120 seconds. The cells were incubated for 24 hours after treatment and viabilities were determined by using a MTT assay. Laser ablation was performed by using the cylindrical light diffuser on six pancreatic tumor tissues obtained from pancreatic cancer xenograft mouse models, which were exposed to the 532 nm light at 5W or 7W for 10 to 30 seconds. In the in vitro study, the survival rates of the pancreatic cancer cells were reduced by 6.6% to 98.9% after the treatment, and the survival rates were reduced by increasing laser power and/or irradiation time. In the pancreatic tumor tissues, a homogenous circular ablation zone was observed in all tumors and the ablation distance induced by the laser irradiation showed to be constant from the diffuser to all directions (standard deviation, 0.3 - 1.3 mm). Ablation distance and area increased with increasing laser power and/or irradiation time. The 532 nm laser effectively killed pancreatic cancer cells, and the cylindrical light diffuser was found to be suitable for laser ablation as it provided uniform ablation in pancreatic cancer.

• Molecules and Cells
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• v.37 no.12
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• pp.888-898
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• 2014

Pancreatic cancer is one of the most fatal cancers and is associated with limited diagnostic and therapeutic modalities. Currently, gemcitabine is the only effective drug and represents the preferred first-line treatment for chemotherapy. However, a high level of intrinsic or acquired resistance of pancreatic cancer to gemcitabine can contribute to the failure of gemcitabine treatment. To investigate the underlying molecular mechanisms for gemcitabine resistance in pancreatic cancer, we performed label-free quantification of protein expression in intrinsic gemcitabine-resistant and -sensitive human pancreatic adenocarcinoma cell lines using our improved proteomic strategy, combined with filter-aided sample preparation, single-shot liquid chromatography-mass spectrometry, enhanced spectral counting, and a statistical method based on a power law global error model. We identified 1931 proteins and quantified 787 differentially expressed proteins in the BxPC3, PANC-1, and HPDE cell lines. Bioinformatics analysis identified 15 epithelial to mesenchymal transition (EMT) markers and 13 EMT-related proteins that were closely associated with drug resistance were differentially expressed. Interestingly, 8 of these proteins were involved in glutathione and cysteine/methionine metabolism. These results suggest that proteins related to the EMT and glutathione metabolism play important roles in the development of intrinsic gemcitabine resistance by pancreatic cancer cell lines.