• Journal of Korean Neurosurgical Society
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• v.38 no.1
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• pp.47-53
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• 2005

Objective : Anti-malaria drugs may modulate tumor resistance to chemotherapeutic agents, but it has not been proven effective in the treatment of malignant gliomas. The aim of this study was to determine whether adequate pre-clinical data on co-administration of chemotherapeutic agents with anti-malaria drugs on malignant cell lines could be obtained that would warrant its further potential consideration for use in a clinical trial for malignant gliomas. Methods : Two malignant glioma cell lines [U87MG, T98G] were treated with chemotherapeutic agents alone or with anti-malaria drugs. Cells were incubated with drugs for 4 days. Following the 4-day incubation, drug sensitivity assays were performed using 3-[4,5-dimethyl-2-thiazol-2-yl] 2,5-diphenyltetrazolium bromide [MTT] assay following optimization of experimental conditions for each cell lines and cell viability was calculated. Results : In all of four chemotherapeutic agents[doxorubicin. vincrisitne, nimustine, and cisplatin], the cell viability was found to be markedly decreased when hydroxychloroquine was co-administered on both U87MG and T98G cell lines. The two way analysis of variance[ANOVA] yielded a statistically significant two-sided p-value of 0.0033[doxorubicin], 0.0005[vincrisitne], 0.0007[nimustine], and 0.0003[cisplatin] on U87MG cell lines and 0.0006[doxorubicin], 0.0421[vincrisitne], 0.0317[nimustine], and 0.0001[cisplatin] on T98G cell lines, respectively. However, treatment with chloroquine and primaquine did not induce a decrease in cell viability on both U87MG and T98G cell lines. Conclusion : Our data support further consideration of the use of hydroxychloroquine prior to systemic chemotherapy to maximize its tumoricidal effect for patients with malignant gliomas.

• Molecules and Cells
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• v.42 no.4
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• pp.292-300
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• 2019

Immunometabolism, defined as the interaction of metabolic pathways with the immune system, influences the pathogenesis of metabolic diseases. Metformin and carbon monoxide (CO) are two pharmacological agents known to ameliorate metabolic disorders. There are notable similarities and differences in the reported effects of metformin and CO on immunometabolism. Metformin, an anti-diabetes drug, has positive effects on metabolism and can exert anti-inflammatory and anti-cancer effects via adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms. CO, an endogenous product of heme oxygenase-1 (HO-1), can exert anti-inflammatory and antioxidant effects at low concentration. CO can confer cytoprotection in metabolic disorders and cancer via selective activation of the protein kinase R-like endoplasmic reticulum (ER) kinase (PERK) pathway. Both metformin and CO can induce mitochondrial stress to produce a mild elevation of mitochondrial ROS (mtROS) by distinct mechanisms. Metformin inhibits complex I of the mitochondrial electron transport chain (ETC), while CO inhibits ETC complex IV. Both metformin and CO can differentially induce several protein factors, including fibroblast growth factor 21 (FGF21) and sestrin2 (SESN2), which maintain metabolic homeostasis; nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of the antioxidant response; and REDD1, which exhibits an anticancer effect. However, metformin and CO regulate these effects via different pathways. Metformin stimulates p53- and AMPK-dependent pathways whereas CO can selectively trigger the PERK-dependent signaling pathway. Although further studies are needed to identify the mechanistic differences between metformin and CO, pharmacological application of these agents may represent useful strategies to ameliorate metabolic diseases associated with altered immunometabolism.

• Journal of Digestive Cancer Research
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• v.12 no.2
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• pp.115-130
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• 2024

The incidence of hepatocellular carcinoma (HCC) is continuously increasing worldwide, with approximately 1 million new cases expected annually by 2025. Data from the Korean Central Cancer Registry in 2023 revealed that the survival rate of patients with HCC was only 40%, unlike patients with other major cancers with a 5-year survival rate of up to 80%, highlighting the need for improved outcomes. The prognosis of HCC significantly changed following research on immune checkpoint inhibitors (ICIs). Several studies have demonstrated that the overall survival of patients treated with first-line combination therapies, such as atezolizumab (anti-PD-L1) and bevacizumab (anti-VEGF) or durvalumab (anti-PD-L1) and tremelimumab (anti-CTLA-4), was higher than that of patients treated with sorafenib. Research to identify biomarkers that can predict ICI responses is ongoing, enabling the selection of suitable patients before drug initiation. Moreover, studies of the tumor microenvironment in HCC enhance our understanding of immune responses, helping us identify new therapeutic strategies. Additionally, clinical trials are being conducted for emerging immunotherapies beyond ICIs, such as adoptive cell therapy. Based on these ongoing scientific researches and the development of various therapeutic modalities, multiple options are being established for patients with HCC who do not respond well to first-line treatments. Consequently, treatment options and survival rates of patients with advanced HCC could be significantly enhanced in the future.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.5
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• pp.687-692
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• 2012

Schizandra chinensis extract has been known to possess a variety of efficacy including antitumor. However, it remains unclear how schizandrin, which is a major biological active ingredient of Schizandra chinensis, exerts antitumor effect. This study was designed to investigate the mechanism by which schizandrin inhibits tumor growth and metastasis. In in vivo test using tumor model mice injected with B16BL6 cell line, mice treated with 10 and 100 ${\mu}g/ml$ schizandrin showed a significant inhibition by $73.79{\pm}6.43%$ and $90.46{\pm}1.72%$, respectively, compared with positive tumor controls. Schizandrin did not exert a significant toxicity for the normal cells (HUVECs) and tumor cell lines (A549, B16BL6, Du145, Huh7). Treatment with schizandrin at 10 and 100 ${\mu}g$/head significantly inhibited the tumor-induced angiogenesis by $68.04{\pm}32.21%$ and $103.8{\pm}34.99%$ compared with the positive control group, respectively. Using in vivo lung metastasis model, tumor metastasis assay revealed that 10 and 100 ${\mu}g$/head schizandrin significantly decreased the metastatic lung tumor by $37.51{\pm}8.15%$ and $75.53{\pm}4.38%$ compared with positive controls, respectively. On the other hand, schizandrin did not affect the adherence of B16BL6 cell line to extracellular matrix protein. These results demonstrate that schizandrin exerts inhibitory effect on tumor growth and metastasis by inhibiting angiogenesis. This study thus suggest that schizandrin may be a candidate molecule target for cancer drug development.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8637-8644
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• 2016

Background: Malignant serous effusions (MSE) are one complication in patients with advanced cancer. Endostar is a new anti-tumor drug targeting vessels which exerts potent inhibition of neovascularization. This study aimed to systematically evaluate the efficacy and safety of intraperitoneal perfusion therapy of Endostar combined with platinum chemotherapy for malignant serous effusions (MSE). Materials and Methods: Randomized controlled trials (RCTs) on intraperitoneal perfusion therapy of Endostar combined with platinum chemotherapy for malignant serous effusions were searched in the electronic data of PubMed, EMBASE, Web of Science, CNKI, VIP, CBM and WanFang. The quality of RCTs was evaluated by two independent researchers and a meta-analysis was performed using RevMan 5.3 software. Results: The total of 25 RCTs included in the meta-analysis covered 1,253 patients, and all literature quality was evaluated as "B" grade. The meta-analysis showed that Endostar combined with platinum had an advantage over platinum alone in terms of response rate of effusions (76% vs 48%, RR=1.63, 95%CI: 1.50-1.78, P<0.00001) and improvement rate in quality of life (69% vs 44%, RR=1.57, 95%CI: 1.42-1.74, P<0.00001). As for safety, there was no significant difference between the two groups in the incidences of nausea and vomiting (35% vs 34%, RR=1.01, 95%CI: 0.87-1.18, P=0.88), leucopenia (38% vs 38%, RR=1, 95%CI: 0.87-1.15, P=0.99), and renal impairment (18% vs 20%, RR=0.86, 95%CI: 0.43-1.74, P=0.68). Conclusions: Endostar combined with platinum by intraperitoneal perfusion is effective for malignant serous effusions, and patient quality of life is significantly improved without the incidence of adverse reactions being obviously increased.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.117-123
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• 2016

Taxol (paclitaxel) is a powerful anti-cancer drug widely used against several types of malignant tumors. Because Taxol may exert several side effects, a variety of formulations have been developed. One of these features liposomes, regarded as one of the most promising drug carriers, biocompatible and best able to reduce drug toxicity without changing efficacy against tumor cells. Eruca sativa seed extract (SE) is considered a promising natural product from cruciferous vegetables against breast cancer, increasing chemotherapeutic and eliminating harmful side effects. The effects of Taxol-encapsulated liposomes (T) alone and in combination between Eruca sativa seed extract on nuclear factor kappa B (NF-${\kappa}B$), cyclooxygenase-2 (COX-2) and B-cell lymphoma-2 (Bcl-2) gene expression levels were investigated in rat mammary gland carcinogenesis induced by 7,12 dimethylbenz(${\alpha}$) anthracene (DMBA) using qRT-PCR. The results showed that DMBA increased NF-${\kappa}B$, COX-2 and Bcl-2 gene expression levels and lipid peroxidation (LP), while decreasing glutathione-S-transferase (GST) and superoxide dismutase (SOD) activities and total antioxidant concentration (TAC) compared to the control group. T and T-SE treatment reduced NF-${\kappa}B$, COX-2 and Bcl-2 gene expression levels and LP. Hence, T and T-SE treatment appeared to reduce inflammation and cell proliferation, while increasing apoptosis, GST and SOD activities and TAC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10705-10711
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• 2015

Oral cancer is one of the most common and lethal cancers in the world. Combination chemotherapy coupled with nanoparticle drug delivery holds substantial promise in cancer therapy. This study aimed to evaluate the efficacy and safety of two dosages of our novel pH and temperature sensitive doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NPs) with attention to the MMP-2 mRNA profile in a 4-nitroquinoline-1-oxide induced oral squamous cell carcinoma (OSCC) model in the rat. Our results showed that both IV and oral dosages of DOX-MTX NP caused significant decrease in mRNA levels of MMP-2 compared to the untreated group (p<0.003). Surprisingly, MMP-2 mRNA was not affected in DOX treated compared to cancer group (p>0.05). Our results indicated that IV dosage of MTX-DOX is more effective than free DOX (12 fold) in inhibiting the activity of MMP-2 in OSCCs (P<0.001). Furthermore, MMP-2 mRNA expression in the DOX-MTX treated group showed a significant relation with histopathological changes (P=0.011). Compared to the untreated cancer group, we observed no pathological changes and neither a significant alteration in MMP-2 amount in either of healthy controls that were treated with oral and IV dosages of DOX-MTX NPs whilst cancer group showed a high level of MMP-2 expression compared to healthy controls (p<0.001).Taking together our results indicate that DOX-MTX NPs is a safe chemotherapeutic nanodrug that its oral and IV forms possess potent anti-cancer properties on aggressive tumors like OSCC, possibly by affecting the expression of genes that drive tumor invasion and metastasis.

• The Journal of Korean Medicine
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• v.27 no.4
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• pp.30-47
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• 2006

Objective : The present study is aimed to elucidate the effects of Cirsium japonicum var. ussuriense on immunomodulation and the potential as an herbal remedy for cancer treatment. Method : It was performed through measurement of effects Cirsium japonicum var. ussuriense extract (CJE) on NO production, NK cell cytotoxicity and cytokine gene expressions related with macrophage and NK cell activity. Result : 1. CJE did not show any direct cytotoxic effects on 7250, HT1080, Hep G2 and CT-26 cells. 2. CJE activated macrophages partially to product NO and up-regulated gene expressions for iNOS in RAW 264.7 cells. 3. CJE promoted cytotoxicity of NK cells against YAC-1 cells at higher concentration than 200 ${\mu}g/ml$. 4. CJE up-regulated gene expressions for $IL-1{\beta}$, IL-2, iNOS, $IFN-{\gamma}$ and $TNF-{\alpha}$ in mice splenocytes.　５. CJE inhibited lung tumor metastasis induced by CT-26 cell transplantation compared with the control group.　Conclusion : It could be concluded that CJE is an effective herbal drug for immune modulating and anti-cancer treatment by promoting activity of macrophages and NK cells.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.213-220
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• 2023

The most common skin disease, acne, often occurs in adolescence, but it is also detected/observed in adults due to air pollution and drug abuse. One of the causative agents of acne, Cutibacterium acnes (C. acnes) plays a role in the development of skin acne by inducing inflammatory mediators. Torreya nucifera (TN) is an evergreen tree of the family Taxaceae, having well reported antioxidant, anti-proliferative, liver protection, and nerve protection properties. Improvement of these bioactive properties of natural products is one of the purposes of natural product chemistry and pharmaceuticals. We believe biorenovation could be one improvement strategy that utilizes microbial metabolism to produce unique derivatives having enhanced bioactivity. Therefore, in this study, the C. acnes-induced RAW264.7 inflammation model was used to evaluate the anti-inflammatory activity of the biorenovated Torreya nucifera product (TNB). The results showed improved viability of TNB-treated cells compared to TN-treated cells in the concentration range of 50, 100, and 200 ㎍/mL. At non-toxic concentrations, TNB inhibited the production of nitric oxide and prostaglandin E2 by suppression of inducible nitric oxide synthase and cyclooxygenase-2 protein expression. TNB also attenuated the expression of interleukin-1β, interleukin-6, interleukin-8, and tumor necrosis factor-α induced by C. acnes. Furthermore, TNB inhibited the nuclear factor-κB signaling pathway, a transcription factor known to regulate inflammatory mediators. Based on these results, this study suggests the potential of using TNB as natural material for the treatment of acnes and thus, supporting our postulation of biorenovation as an bioactivity improvement strategy.

• The Journal of Internal Korean Medicine
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• v.36 no.1
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• pp.13-21
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• 2015

Objectives : In Korea, Rhus verniciflua Stokes (RVS) has been used in traditional medicine for various diseases such as back pain, syndromes of the blood system in women, gastrointestinal disease, and cancer. However, the molecular mechanisms of its anti-cancer activity have not been clearly elucidated yet. Methods : This study investigated the possible mechanisms by which RVS extract (RVE) exerts its anti-proliferative action in cultured human breast carcinoma MCF-7 cells. Results : Treatment with RVE in MCF-7 cells resulted in inhibition of cell viability through G1 arrest of the cell cycle and induction of apoptosis in a time- and concentration-dependent manner, as determined by MTT assay and flow cytometry analysis. The induction of G1 arrest by RVE treatment was associated with the inhibition of cyclin D1, cyclin-dependent kinase (Cdk) 2, retinoblastoma protein (pRB), and mouse double minute 2 (MDM2) expression. Moreover, RVE treatment concentration dependently increased the levels of tumor suppressor p53, which was associated with the marked induction of Cdk inhibitors such as p21 (Waf1/Cip1) and p27 (Kip1). However, the inhibition of p53 function by the wild-type p53-specific inhibitor, pifithrin-α, abolished the above-mentioned effects of RVE, showing that p53 was responsible for the cytotoxicity of RVE Conclusions : These data indicate that a molecular pathway involving p53-dependent G1 cell cycle arrest plays a pivotal role in the cellular response to RVE, and demonstrate the potential applications of RVE as an anti-cancer drug for breast cancer treatment.