• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.2
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• pp.518-522
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• 2007

The cortex and root of Acnthopanax sessiliflorus, a herbal medicine, have been used for several diseases including cancer in Oriental countries. In the previous study, we showed that the cortex of this plant have anti-cancer activity. But its therapeutic efficacy of CORTEX ACANTHOPANAX RADICIS (CAR) is not clarified. For these reasons, we investigated immuno-potentiating and anti-cancer properties of CAR compared with CA, in terms of body and tumor weights, proliferation of thymocytes and tumor cells, and nitric oxide production from macrophages through in vitro and in vivo studies. In our results, administration of CAR reduced tumor mass and increased body weights. CAR also inhibited proliferation of tumor cells in vivo and in vitro dose-dependently. Thymocyte proliferation was accelerated by treatment with CAR and NO production was also promoted by CAR in vivo and vitro. In conclusion, we demonstrated that CAR is useful to treat for cancer as complementary or alternative medicine to Western medication, its therapeutic efficacy is involved in direct inhibition of tumor growth and immuno-potentiating activity.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9249-9258
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• 2014

Background: The encapsulation of curcumin (Cur) in polylactic-co-glycolic acid (PLGA) nanoparticles (Cur-NPs) was designed to improve its solubility and stability. Conjugation of the Cur-NPs with anti-P-glycoprotein (P-gp) antibody (Cur-NPs-APgp) may increase their targeting to P-gp, which is highly expressed in multidrugresistance (MDR) cancer cells. This study determined whether Cur-NPs-APgp could overcome MDR in a human cervical cancer model (KB-V1 cells) in vitro and in vivo. Materials and Methods: First, we determined the MDR-reversing property of Cur in P-gp-overexpressing KB-V1 cells in vitro and in vivo. Cur-NPs and Cur-NPs-APgp, in the range 150-180 nm, were constructed and subjected to an in vivo pharmacokinetic study compared with Cur. The in vitro and in vivo MDR-reversing properties of Cur-NPs and Cur-NPs-APgp were then investigated. Moreover, the stability of the NPs was determined in various solutions. Results: The combined treatment of paclitaxel (PTX) with Cur dramatically decreased cell viability and tumor growth compared to PTX treatment alone. After intravenous injection, Cur-NPs-APgp and Cur-NPs could be detected in the serum up to 60 and 120 min later, respectively, whereas Cur was not detected after 30 min. Pretreatment with Cur-NPs-APgp, but not with NPs or Cur-NPs, could enhance PTX sensitivity both in vitro and in vivo. The constructed NPs remained a consistent size, proving their stability in various solutions. Conclusions: Our functional Cur-NPs-APgp may be a suitable candidate for application in a drug delivery system for overcoming drug resistance. The further development of Cur-NPs-APgp may be beneficial to cancer patients by leading to its use as either as a MDR modulator or as an anticancer drug.

• YAKHAK HOEJI
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• v.53 no.6
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• pp.303-313
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• 2009

Traditionally, Cham dang-gui (Angelica gigas Nakai) is one of the most popular herbal medicines in Asian countries including Korea. A. gigas has been used as a functional food product for treatment anemia, women's health care, a sedative, an anodyne or a tonic agent. Decursin and decursinol angelate isolated from the roots of A. gigas are pyranocoumarin compounds. Recently, as the global herbal medication market is increasing, investigations about pharmacological effects of decursin and decursinol angelate are rapidly increasing. We summarized previous studies about pharmacological effects of decursin and decursinol angelate, and reviewed relation with pharmacological effects of decursin and decursinol angelate on human disorder, focused on the approach for new drug development. Pharmacological effects of decursin and decursinol angelate were classified as anti-tumor activity, anti-bacterial activity, improvements of the circulating system, inhibition of cytochrome P-450 activity, anti-inflammation activity, anti-oxidant activity and cognitive-enhancing activites. The activity of A. gigas with improvement of the circulating system may have wide therapeutic potential for circulatory diseases, including diabetes, hyperlipidemia and atherosclerosis. Also, anti-inflammation activity A. gigas may be beneficial for the treatment and prevention of asthma, atopic dermatitis and rheumatism arthritis. This relation could potentially lead to the development of herbal new drugs. In order to development a new drug containing decursin and decursinol angelate, it is also necessary to consider the safety profile, and the information in this review would contribute to development a new drug from herbal medicine.

• IMMUNE NETWORK
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• v.15 no.2
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• pp.58-65
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• 2015

Melanoma is the most aggressive skin cancer and its incidence is gradually increasing worldwide. Patients with metastatic melanoma have a very poor prognosis (estimated 5-year survival rate of <16%). In the last few years, several drugs have been approved for malignant melanoma, such as tyrosine kinase inhibitors and immune checkpoint blockades. Although new therapeutic agents have improved progression-free and overall survival, their use is limited by drug resistance and drug-related toxicity. At the same time, adoptive cell therapy of metastatic melanoma with tumor-infiltrating lymphocytes has shown promising results in preclinical and clinical studies. In this review, we summarize the currently available drugs for treatment of malignant melanoma. In addition, we suggest cytokine-induced killer (CIK) cells as another candidate approach for adoptive cell therapy of melanoma. Our preclinical study and several previous studies have shown that CIK cells have potent anti-tumor activity against melanomas in vitro and in an in vivo human tumor xenograft model without any toxicity.

• BMB Reports
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• v.56 no.11
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• pp.612-617
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• 2023

Pleiotropic regulator 1 (PLRG1), a highly conserved element in the spliceosome, can form a NineTeen Complex (NTC) with Prp19, SPF27, and CDC5L. This complex plays crucial roles in both pre-mRNA splicing and DNA repair processes. Here, we provide evidence that PLRG1 has a multifaceted impact on cancer cell proliferation. Comparing its expression levels in cancer and normal cells, we observed that PLRG1 was upregulated in various tumor tissues and cell lines. Knockdown of PLRG1 resulted in tumor-specific cell death. Depletion of PLRG1 had notable effects, including mitotic arrest, microtubule instability, endoplasmic reticulum (ER) stress, and accumulation of autophagy, ultimately culminating in apoptosis. Our results also demonstrated that PLRG1 downregulation contributed to DNA damage in cancer cells, which we confirmed through experimental validation as DNA repair impairment. Interestingly, when PLRG1 was decreased in normal cells, it induced G1 arrest as a self-protective mechanism, distinguishing it from effects observed in cancer cells. These results highlight multifaceted impacts of PLRG1 in cancer and underscore its potential as a novel anti-cancer strategy by selectively targeting cancer cells.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4751-4756
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• 2012

Colon cancer continues to be one of the most common cancers, and the importance and necessity of new therapies needs to be stressed. The most important proto-oncogen factors for colon cancer appear to be epidermal growth factor receptor, EGFR, and c-Src with high expression and activity leading to tumor growth and ultimately to colon cancer progression. Application of c-Src and EGFR antisense agents simultaneously should theoretically therefore have major benefit. In the present study, anti-EGFR and c-Src specific antisense oligodeoxynucleotides were combined in a formulation using PAMAM dendrimers as a carrier. Nano drug entry into cells was confirmed by flow cytometry and fluorescence microscopy imaging and real time PCR showed gene expression of c-Src and EGFR, as well as downstream STAT5 and MAPK-1 with the tumor suppressor gene P53 to all be downregulated. EGFR and c-Src protein expression was also reduced when assessed by western blotting techniques. The effect of the antisense oligonucleotide on HT29 cell proliferation was determined by MTT assay, reduction beijng observed after 48 hours. In summary, nano-drug, anti-EGFR and c-Src specific antisense oligodeoxynucleotides were effectively transferred into HT-29 cells and inhibited gene expression in target cells. Based on the results of this study it appears that the use of antisense EGFR and c-Src simultaneously might have a significant effect on colon cancer growth by down regulation of EGFR and its downstream genes.

• Bulletin of the Korean Chemical Society
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• v.35 no.10
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• pp.3030-3034
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• 2014

Bis-chloroethylnitrosourea (BCNU) is currently used as an anti-cancer drug for glioblastoma therapy. In this study, BCNU was loaded into the hydrophobic cores of R3V6 amphiphilic peptide micelles for efficient delivery into brain tumors. The scanning electron microscope (SEM) study showed that the BCNU-loaded R3V6 peptide micelles (R3V6-BCNU) formed spherical micelles. MTT assay showed that R3V6-BCNU more efficiently induced cell death in C6 glioblastoma cells than did BCNU. In the Annexin V assay, R3V6-BCNU more efficiently induced apoptosis than did BCNU alone. Furthermore, the results showed that R3V6 was not toxic to cells. The positive charges of the R3V6 peptide micelles may facilitate the interaction between R3V6-BCNU and the cellular membrane, resulting in an increase in cellular uptake of BCNU. In vivo evaluation with an intracranial glioblastoma rat model showed that R3V6-BCNU more effectively reduced tumor size than BCNU alone. The results suggest that R3V6 peptide micelles may be an efficient carrier of BCNU for glioblastoma therapy.

• Oncology Letters
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• v.18 no.3
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• pp.3256-3264
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• 2019

The induction of apoptosis is a useful strategy in anti-cancer research. Various Moon Hyung Yang (MHY) compounds have been developed as novel anti-cancer drug candidates; in the present study, the pro-apoptotic effects of (Z)-5-(3-ethoxy-4-hydroxybenzylidene)-2-thioxothiazolidin-4-one (MHY695) on HCT116 human colon cancer cells were assessed. MTT assays were performed to investigate the dose-dependent cytotoxic effects of MHY695 on HCT116 cells. Immunofluorescence staining and flow cytometry analyses were performed to identify apoptotic cell death, and western blot analysis was used to investigate the apoptotic-signaling pathways. A mouse xenograft model was also used to determine the effects of MHY695 in vivo. MHY695 decreased the viability of HCT116 cells and induced apoptotic cytotoxicity. The apoptotic mechanisms induced by MHY695 involved the dephosphorylation of Bcl-2-associated agonist of cell death protein following protein kinase B inactivation, induced myeloid leukaemia cell differentiation protein and BH3-interacting domain death agonist truncation, caspase-3 and -9 activation and poly (ADP-ribose) polymerase cleavage. In addition, MHY695 significantly suppressed tumor growth in the mouse xenograft model, compared with the vehicle control. Notably, MHY695 exhibited potent anti-cancer effects in four different types of human colon cancer cell line, including Caco-2, DLD-1, HT-29 and HCT116. Additionally, MHY695 showed reduced cytotoxicity in NCM460, normal colonic epithelial cells. Furthermore, MHY-induced cytotoxicity in colon cancer cells was independent of the tumor suppressor protein p53. Collectively, these observations suggested that MHY695 may be a novel drug for the treatment of colon cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.6991-6996
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• 2015

In the past decade, the incidence and mortality rates of cholangiocarcinoma (CCA) have been increasing worldwide. The relatively low responsiveness of CCA to conventional chemotherapy leads to poor overall survival. Recently, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) has emerged as the most promising anti-cancer therapeutic agent since it is able to selectively induce apoptosis of tumor cells but not normal cells. In this study, we aimed to investigate the therapeutic effect of TRAIL in CCA cell lines (M213, M214 and KKU100) compared with the immortal biliary cell line, MMNK1, either alone or in combination with a subtoxic dose of 5-fluorouracil (5-FU). We found that recombinant human TRAIL (rhTRAIL) was a potential agent which significantly inhibited cell proliferation and mediated caspase activities (caspases 8, 9 and 3/7) and apoptosis of CCA cells. The combined treatment of rhTRAIL and 5-FU effectively enhanced inhibition of CCA cell growth with a smaller effect on MMNK1. Our finding suggests TRAIL to be a novel anti-cancer therapeutic agent and advantage of its combination with a conventional chemotherapeutic drug for effective treatment of CCA.

• Laboraroty Animal Research
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• v.34 no.4
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• pp.160-165
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• 2018

Breast cancer remains the second leading cause of cancer death among woman, worldwide, despite advances in identifying novel targeted therapies and the development of treating strategies. Classification of clinical subtypes (ER+, PR+, HER2+, and TNBC (Triple-negative)) increases the complexity of breast cancers, which thus necessitates further investigation. Mouse models used in breast cancer research provide an essential approach to examine the mechanisms and genetic pathway in cancer progression and metastasis and to develop and evaluate clinical therapeutics. In this review, we summarize tumor transplantation models and genetically engineered mouse models (GEMMs) of breast cancer and their applications in the field of human breast cancer research and anti-cancer drug development. These models may help to improve the knowledge of underlying mechanisms and genetic pathways, as well as creating approaches for modeling clinical tumor subtypes, and developing innovative cancer therapy.