• The Korean Journal of Applied Statistics
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• v.6 no.2
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• pp.383-391
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• 1993

Interaction between anti-cancer agents and various modulators of multidrug resistance in producing their joint effects are of fundamental interest in the chemtherapeutic treatment of cancer. We generate a dose-response curve for each combination of several anti-cancer agents and modulators based on an in-vitro experiment on each of several human cancer cell lines. We employ a log-linear model developed by Wahrendorf et al (1981) and Piegorsch et al (1988) to detect synergism among several compounds. We show two examples of the data analysis and their results. We believe that these results encourage further experiment in-vivo studies.

• Journal of Mushroom
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• v.20 no.3
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• pp.93-101
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• 2022

Cordyceps militaris mycelium extracts containing high amounts of cordycepin were evaluated in vitro for their anti-inflammatory and tumor cell growth-inhibitory activities. All extracts dose dependently inhibited the increased production of inflammatory mediators including reactive oxygen species (ROS), nitric oxide (NO), and 𝛽-hexosaminidase in lipopolysaccharide (LPS)-stimulated inflammatory cells. All extracts were evaluated for anti-proliferative activity against normal RBL-2H3 cells and diverse types of cancer cell lines, including HCT, MC5-7, U-87MG, AGS, and A549 cells. The extract showed the strongest growth inhibition (IC₅₀ = 28.13 ㎍/mL) relative to vehicle-treated control cells against fibrosarcoma (MC5-7). We have demonstrated anti-inflammatory activity of C. militaris via inhibition of NO, ROS production, and 𝛽-hexosaminidase release in activated cells. C. militaris mycelium extract was also evaluated mechanistically and found to exert six types of anti-cancer activity, confirming its pharmacological potential. Our study suggests C. militaris use as a potential source of anti-inflammatory and anti-cancer agents. C. militaris may also be considered a functional food.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5855-5860
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• 2013

Phytochemicals are among the natural chemopreventive agents with most potential for delaying, blocking or reversing the initiation and promotional events of carcinogenesis. They therefore offer cancer treatment strategies to reduce cancer related death. One such promising chemopreventive agent which has attracted considerable attention is sulforaphane (SFN), which exhibits anti-cancer, anti-diabetic, and anti-microbial properties. The present study was undertaken to assess effect of SFN alone and in combination with a chemotherapeutic agent, gemcitabine, on the proliferative potential of MCF-7 cells by cell viability assay and authenticated the results by nuclear morphological examination. Further we analyzed the modulation of expression of Bcl-2 and COX-2 on treatment of these cells with SFN by RT-PCR. SFN showed cytotoxic effects on MCF-7 cells in a dose- and time-dependent manner via an apoptotic mode of cell death. In addition, a combinational treatment of SFN and gemcitabine on MCF-7 cells resulted in growth inhibition in a synergistic manner with a combination index (CI)<1. Notably, SFN was found to significantly downregulate the expression of Bcl-2, an anti-apoptotic gene, and COX-2, a gene involved in inflammation, in a time-dependent manner. These results indicate that SFN induces apoptosis and anti-inflammatory effects on MCF-7 cells via downregulation of Bcl-2 and COX-2 respectively. The combination of SFN and gemcitabine may potentiate the efficacy of gemcitabine and minimize the toxicity to normal cells. Taken together, SFN may be a potent anti-cancer agent for breast cancer treatment.

• Fisheries and Aquatic Sciences
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• v.21 no.8
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• pp.22.1-22.7
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• 2018

Background: Apoptosis is a process of programmed cell death, and apoptosis defect results in serious diseases such as cancer. Apoptosis induction is one of the key mechanisms of anti-cancer agents. This study was aimed to find anti-prostate cancer compounds from marine-derived fungus Microsporum sp. Results: We found that physcion isolated from the fermentation broth extract of the marine fungus Microsporum sp. strain MFS-YL decreases the cell proliferation of PC3 human prostate cancer cells. Physcion induced cell apoptosis as determined by Annexin V/propidium iodide double staining. Physcion downregulated the anti-apopotoic proteins such as Ras, Bcl-xL, and Bcl-2, whereas upregulated the pro-apoptotic Bax. Physcion also activated caspase-3, caspase-8, and caspase-9. Conclusion: These results suggest that physcion from Microsporum sp. inhibits the proliferation of PC3 human prostate cancer cells via the pathway leading to apoptotic cell death. Physcion may be a potential candidate in the field of anticancer drug discovery against human prostate cancer.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.5
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• pp.377-387
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• 2022

Benzimidazole anthelmintic agents have been recently repurposed to overcome cancers resistant to conventional therapies. To evaluate the anti-cancer effects of benzimidazole on resistant cells, various cell death pathways were investigated in 5-fluorouracil-resistant colorectal cancer cells. The viability of wild-type and 5-fluorouracil-resistant SNU-C5 colorectal cancer cells was assayed, followed by Western blotting. Flow cytometry assays for cell death and cell cycle was also performed to analyze the anti-cancer effects of benzimidazole. When compared with albendazole, fenbendazole showed higher susceptibility to 5-fluorouracil-resistant SNU-C5 cells and was used in subsequent experiments. Flow cytometry revealed that fenbendazole significantly induces apoptosis as well as cell cycle arrest at G2/M phase on both cells. When compared with wild-type SNU-C5 cells, 5-fluorouracil-resistant SNU-C5 cells showed reduced autophagy, increased ferroptosis and ferroptosis-augmented apoptosis, and less activation of caspase-8 and p53. These results suggest that fenbendazole may be a potential alternative treatment in 5-fluorouracil-resistant cancer cells, and the anticancer activity of fenbendazole does not require p53 in 5-fluorouracil-resistant SNU-C5 cells.

• Biomolecules & Therapeutics
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• v.20 no.1
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• pp.81-88
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• 2012

Histone deacetylases (HDACs) are enzymes involved in the remodelling of chromatin, and have a key role in the epigenetic regulation of gene expression. Histone deacetylase (HDAC) inhibitors are emerging as an exciting new class of potential anti-cancer agents. In recent years, a number of structurally diverse HDAC inhibitors have been identifi ed and these HDAC inhibitors induce growth arrest, differentiation and/or apoptosis of cancer cells in vitro and in vivo. However, the underlying molecular mechanisms remain unclear. This study aimed at investigating the anti-tumor activity of various HDAC inhibitors, IN-2001, using T47D human breast cancer cells. Moreover, the possible mechanism by which HDAC inhibitors exhibit anti-tumor activity was also explored. In estrogen receptor positive T47D cells, IN-2001, HDAC inhibitor showed anti-proliferative effects in dose-and time-dependent manner. In T47D human breast cancer cells showed anti-tumor activity of IN-2001 and the growth inhibitory effects of IN-2001 were related to the cell cycle arrest and induction of apoptosis. Flow cytometry studies revealed that IN-2001 showed accumulation of cells at $G_2$/M phase. At the same time, IN-2001 treatment time-dependently increased sub-$G_1$ population, representing apoptotic cells. IN-2001-mediated cell cycle arrest was associated with induction of cdk inhibitor expression. In T47D cells, IN-2001 as well as other HDAC inhibitors treatment significantly increased $p21^{WAF1}$ and $p27^{KIP1}$ expression. In addition, thymidylate synthase, an essential enzyme for DNA replication and repair, was down-regulated by IN-2001 and other HDAC inhibitors in the T47D human breast cancer cells. In summary, IN-2001 with a higher potency than other HDAC inhibitors induced growth inhibition, cell cycle arrest, and eventual apoptosis in human breast cancer possibly through modulation of cell cycle and apoptosis regulatory proteins, such as cdk inhibitors, cyclins, and thymidylate synthase.

• Advances in nano research
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• v.10 no.2
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• pp.139-150
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• 2021

In this study, phytochemicals present in Propolis Extract (PE) were employed as reducing and stabilizing reagents to synthesize silver nanoparticles. Three propolis-reduced silver nanoparticles (P-AgNPs1-3) were synthesized using increasing amounts of PE. P-AgNPs were treated with different cancer cells-lung (A549), cervix (HeLa) and colon (WiDr) - for 24, 48 and 72 h to evaluate their anti-proliferative activities. A non-cancerous cell type (L929) was also used to test whether suppressive effects of P-AgNPs on cancer cell proliferation were due to a general cytotoxic effect. The characterization results showed that the bioactive contents in propolis successfully induced particle formation. As the amount of PE increased, the particle size decreased; however, the size distribution range expanded. The antioxidant capacity of the particles increased with increased propolis amounts. P-AgNP1 exhibited almost equal inhibitory effects across all cancer cell types; however, P-AgNP2 was more effective on HeLa cells. P-AgNPs3 showed greater inhibitory effects in almost all cancer cells compared to other NPs and pure propolis. Consequently, the biological effects of P-AgNPs were highly dependent on PE amount, NP concentration, and cell type. These results suggest that AgNPs synthesized utilizing propolis phytochemicals might serve as anti-cancer agents, providing greater efficacy against cancer cells.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1331-1336
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• 2015

Natural glycoproteins can induce apoptosis of tumor cells and exert anti-tumor activity by immunomodulatory functions, cytotoxic and anti-inflammation effects, and inhibition of endothelial growth factor. Given their prospects as novel agents, sources of natural antitumor glycoproteins have attracted attention and new research directions in glycoprotein biology are gradually shifting to the direction of cancer treatment and prevention of neoplastic disease. In this review, we summarize the latest findings with regard to the tumor suppressor signature of glycoproteins and underlying regulatory mechanisms.

• IMMUNE NETWORK
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• v.20 no.1
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• pp.3.1-3.20
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• 2020

Immune checkpoint inhibitors (ICIs), including anti-PD-1 and anti-CTLA-4 therapeutic agents, are now approved by the Food and Drug Administration for treatment of various types of cancer. However, the therapeutic efficacy of ICIs varies among patients and cancer types. Moreover, most patients do not develop durable antitumor responses after ICI therapy due to an ephemeral reversal of T-cell dysfunction. As co-stimulatory receptors play key roles in regulating the effector functions of T cells, activating co-stimulatory pathways may improve checkpoint inhibition efficacy, and lead to durable antitumor responses. Here, we review recent advances in our understating of co-stimulatory receptors in cancers, providing the necessary groundwork for the rational design of cancer immunotherapy.

• Biomolecules & Therapeutics
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• v.29 no.3
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• pp.331-341
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• 2021

Liver cancer is a common tumor and currently the second leading cause of cancer-related mortality globally. Liver cancer is highly related to inflammation as more than 90% of liver cancer arises in the context of hepatic inflammation, such as hepatitis B virus and hepatitis C virus infection. Despite significant improvements in the therapeutic modalities for liver cancer, patient prognosis is not satisfactory due to the limited efficacy of current drug therapies in anti-metastatic activity. Therefore, developing new effective anti-cancer agents with anti-metastatic activity is important for the treatment of liver cancer. In this study, SP-8356, a verbenone derivative with anti-inflammatory activity, was investigated for its effect on the growth and migration of liver cancer cells. Our findings demonstrated that SP-8356 inhibits the proliferation of liver cancer cells by inducing apoptosis and suppressing the mobility and invasion ability of liver cancer cells. Functional studies revealed that SP-8356 inhibits the mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways, which are related to cell proliferation and metastasis, resulting in the downregulation of metastasis-related genes. Moreover, using an orthotopic liver cancer model, tumor growth was significantly decreased following treatment with SP-8356. Thus, this study suggests that SP-8356 may be a potential agent for the treatment of liver cancer with multimodal regulation.