• 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.

• BMB Reports
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• v.45 no.4
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• pp.242-246
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• 2012

The use of ionizing radiation (IR) is essential for treating many human cancers. However, radioresistance markedly impairs the efficacy of tumor radiotherapy. IR enhances the production of reactive oxygen species (ROS) in a variety of cells which are determinant components in the induction of apoptosis. Much interest has developed to augment the effect of radiation in tumors by combining it with radiosensitizers to improve the therapeutic ratio. In the current study, the radiosensitizing effects of resveratrol and piperine on cancer cells were evaluated. Cancer cell lines treated with these natural products exhibited significantly augmented IR-induced apoptosis and loss of mitochondrial membrane potential, presumably through enhanced ROS generation. Applying natural products as sensitizers for IR-induced apoptotic cell death offers a promising therapeutic approach to treat cancer.

• Natural Product Sciences
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• v.7 no.2
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• pp.60-62
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• 2001

Ulmus davidiana, Formitella fraxinea, and Aloe vera extracts were detected to have inhibitory effects against topoisomerase I at treatment of $5{\mu}g$. Ulmus davidiana and Aloe vera extracts were found to show inhibitory effect similar to camptothecin, Formitella fraxinea extract was found to have weak activity. We also found the potential use of those extracts as a radiation sensitizer. Radiosensitizing effect at combination treatment was increased more than 2 times at single treatment of radiation, Ulmus davidiana or Formitella fraxinea extracts. Ulmus davidiana and Formitella fraxinea extracts were found to have significant radiosensitizing effect on test tumor cell line. But, Aloe vera extract was not detected to have activity as a radiosensitizer. Ulmus davidiana and Formitella fraxinea extracts are potent radiosensitizers on tumor cell lines and should be considered for further study of active compounds.

• Biomolecules & Therapeutics
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• v.23 no.5
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• pp.428-433
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• 2015

Acetylshikonin, a natural naphthoquinone derivative compound, has been used for treatment of inflammation and cancer. In the present study, we have investigated whether acetylshikonin could regulate the NF-${\kappa}B$ signaling pathway, thereby leading to suppression of tumorigenesis. We observed that acetylshikonin significantly reduced proliferation of several cancer cell lines, including human pancreatic PANC-1 cancer cells. In addition, acetylshikonin inhibited phorbol 12-myristate 13-acetate (PMA) or tumor necrosis-${\alpha}$ (TNF-${\alpha}$)-induced NF-${\kappa}B$ reporter activity. Proteome cytokine array and real-time RT-PCR results illustrated that acetylshikonin inhibition of PMA-induced production of cytokines was mediated at the transcriptional level and it was associated with suppression of NF-${\kappa}B$ activity and matrix metalloprotenases. Finally, we observed that an exposure of acetylshikonin significantly inhibited the anchorage-independent growth of PANC-1 cells. Together, our results indicate that acetylshikonin could serve as a promising therapeutic agent for future treatment of pancreatic cancer.

• YAKHAK HOEJI
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• v.47 no.6
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• pp.376-381
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• 2003

2-Arylchromones, also known as flavones, are among the most ubiquitous classes of natural products occurring in the plant kingdom. On the other hand, 2-styrylchromones are relatively scarce in nature and only a few compounds has been isolated from the blue-green algae species. Therefore, new 2-arylethenylchromone derivatives ( 4a∼n, 5a∼f) were synthesized by the aldol condensation of 2-methylchromone ( 3) with several aromatic aldehydes in order to evaluate their cytotoxicities using a MTT assay on three tumor cells. 2-Arylethenylchromone derivative 4a showed the significant cytotoxic activities on KB, HL-60 and P-388 cell lines with $IC_{50}$/ values of 25.2, 63.59 and 49.51 $\mu$M, respectively, indicating that 2-arylethenylchromone skeleton has a potential anti-tumor application.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.190.1-190.1
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• 2003

A bioassay-guided fractionation of the stem bark extract of Eucommia ulmoides Oliver (Eucommiaceae) led to the isolation of three iridoid constituents, genipin (1), geniposide (3), geniposidic acid (4) as well as (${\pm}$)-guaiacylglycerol (2) and fatty acid mixtures as active ingredients of the extract responsible for the antitumoral property. The EtOAc soluble part and BuOH soluble part of the extract demonstrated a significant inhibition on the proliferation of cultured human tumor cells such as A549 (non small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central nerve system) and HCT-15 (colon) in vitro, whereas the remaining water soluble part exhibited a poor inhibition. (omitted)

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.202.2-202.2
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• 2003

A bioassay-guided fractionation of the whole extract of Viscum album (a parasitic plant : Loranthaceae) led to the isolation of two triterpenoidal components, oleanolic acid (1), ${\beta}$-amyrin acetate (2), homoflavoyadorinin B (3) as well as large quantity of free fatty acid mixtures as active ingredients of the extract responsible for the antitumoral property. The EtOAc soluble part and BuOH soluble part of the extract demonstrated a significant inhibition on the proliferation of cultured human tumor cells such as A549 (non small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central nerve system) and HCT-15 (colon) in vitro, whereas the remaining water soluble part exhibited a poor inhibition. (omitted)

• Tuberculosis and Respiratory Diseases
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• v.40 no.6
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• pp.653-658
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• 1993

Background: Recent advancement of molecular genetics has revealed that malignant transformation of a cell may be a complex multistep process and this process is grouped, in general, into two distinct categories, activation of protooncogenes and inactivation of tumor suppressor genes. This study was focused on the mutation of p53 tumor suppressor gene, because p53 gene mutation is now generally accepted to be one of the most frequent genetic changes in a variety of human cancers. Although lung cancer is one of the common cancers in Korea, the genetic change in the carcinogenesis process is not yet known clearly. To investigate the role of p53 gene mutation in lung cancer, we examined the mutations of exon 4-8 of the p53 gene in humna lung cancer cell lines, because most of the mutations of p53 gene have been reported to develop in exon 4-8. Method: Genomic DNA was obtained by the digestion of proteinase K and the extraction by phenol-chloroform-ethanol method from two human pulmonary adenocarcinoma cell lines, PC-9 and PC-14, and one human small cell lung cancer cell line, H69. To detect the mutations of exon 4-8 of the p53 gene, polymerase chain reaction single-strand conformation polymorphism(PCR-SSCP) analysis was performed with the DNA extracted from the cells. Results: The mutation of p53 gene was present in all three cell lines tested. In PC-9, PC-14 and H69, the altered mobility was detected in exon 7, 7 and 5, respectively. Conclusion: These results suggest that p53 gene mutation plays an important role in certain steps of the carcinogenesis of human non-small cell and small cell lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1715-1717
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• 2014

The overall incidence and mortality of renal cell carcinoma (RCC), the most common kidney cancer, are steadily increasing for reasons that are not fully explained. Our aim was to explore the expression of membrane MHC class I chain-related gene A (mMICA) in human RCC cell lines and tissue specimens, and to determine expression of soluble MICA (sMICA) in serum of patients with renal cell carcinoma, we used flow cytometry (FCM) and immunohistochemistry as well as an enzyme linked immunosorbent assay (ELISA). The results showed that percentage of mMICA expression was significantly increased in human kidney cancer tissues and RCC cell lines (786-O and Ketr-3) than that in healthy adults and human embryonic kidney 293 (HEK293) cell line individuality (P<0.05). sMICA content in healthy adults was negative, but in renal cancer patients was significantly elevated (P<0.05). Our research showed that high expression of MICA in human kidney cancer, this results show that MICA might serve as potential tumor-associated antigen (TAA) in RCC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7553-7558
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• 2014

The Piwi subfamily comprises two argonaute (Ago) family proteins, which are defined by the presence of PAZ and Piwi domains, with well known roles in RNA silencing. Hiwi, a human Piwi subfamily member, has been shown to play essential roles in stem cell self-renewal and gametogenesis. Recently, accumulating reports have indicated that abnormal hiwi expression is associated with poorer prognosis of multiple types of human cancers, including examples in the breast. However, little is known about details of the oncogenic role of hiwi in breast cancers. In present study, we confirmed overexpression of hiwi in breast cancer specimens and breast cancer cell lines at both mRNA and protein levels. Thus both RT-qPCR and Western blot data revealed significantly higher hiwi in intratumor than peritumor specimens, overexpression being associated with tumor size, lymph node metastasis and histological grade. Hiwi overexpression was also identified in breast cancer cell lines, MDA-MB-231 and MCF-7, and gain-of-function and loss-of-function strategies were adopted to identify the role of hiwi in the MCF-7 cell growth. Results demonstrated that hiwi expression in MCF-7 cells was significantly up- or down-regulated by the two strategies. We next evaluated the influence of hiwi overexpression or knockdown on the growth of breast cancer cells. Both cell count and colony formation assays confirmed promoting roles of hiwi in MCF-7 cells, which could be inhibited by hiwi specific blockage by siRNAs. In summary, the present study confirmed overexpression of hiwi in breast cancer specimens and breast cancer cell lines, and provided e vidence of promotion by hiwi of cell growth. The results imply an oncogenic role of hiwi in breast cancers.