• Molecules and Cells
• /
• v.43 no.7
• /
• pp.662-670
• /
• 2020

We have investigated the involvement of the pre-mRNA processing factor 4B (PRP4) kinase domain in mediating drug resistance. HCT116 cells were treated with curcumin, and apoptosis was assessed based on flow cytometry and the generation of reactive oxygen species (ROS). Cells were then transfected with PRP4 or pre-mRNA-processing-splicing factor 8 (PRP8), and drug resistance was analyzed both in vitro and in vivo. Furthermore, we deleted the kinase domain in PRP4 using Gateway™ technology. Curcumin induced cell death through the production of ROS and decreased the activation of survival signals, but PRP4 overexpression reversed the curcumin-induced oxidative stress and apoptosis. PRP8 failed to reverse the curcumin-induced apoptosis in the HCT116 colon cancer cell line. In xenograft mouse model experiments, curcumin effectively reduced tumour size whereas PRP4 conferred resistance to curcumin, which was evident from increasing tumour size, while PRP8 failed to regulate the curcumin action. PRP4 overexpression altered the morphology, rearranged the actin cytoskeleton, triggered epithelial-mesenchymal transition (EMT), and decreased the invasiveness of HCT116 cells. The loss of E-cadherin, a hallmark of EMT, was observed in HCT116 cells overexpressing PRP4. Moreover, we observed that the EMT-inducing potential of PRP4 was aborted after the deletion of its kinase domain. Collectively, our investigations suggest that the PRP4 kinase domain is responsible for promoting drug resistance to curcumin by inducing EMT. Further evaluation of PRP4-induced inhibition of cell death and PRP4 kinase domain interactions with various other proteins might lead to the development of novel approaches for overcoming drug resistance in patients with colon cancer.

• Journal of Industrial Technology
• /
• v.25 no.B
• /
• pp.241-251
• /
• 2005

Exopolysaccharide (CBP) from submerged culture broth of Ganoderma lucidum mycelium and the water soluble (BWS) and water insoluble (BWI) fractions of CBP were prepared by gel filtration. Antitumor activity and effects on proliferation and differenciation of human cancer cells and mouse NIH 3T3 cells were studied. Cytotoxicity test of CBP, BWS and BWI fractions on human cancer cell lines was performed by using sulforhodamine B (SRB) assay. A549 (lung carcinoma), Colo320 DM and HSR (colon carcinoma), and NIH 3T3 cells were used. BWI fraction showed the strongest cytotoxicity (maximum 20% survival) to all human cells tested. However it did not induced apoptosis. Interestingly BWI fraction did not exert cytotoxic effect on NIH 3T3 cells at low concentration of cells ($5{\times}10^4$) but strong toxic effect at high concentration of cells($5{\times}10^5$) which showed transformed morphology. These results suggest that BWI may have cancer cell specific anticancer activity. However, BWI fraction did not effect the amount of pRb and c-myc protein, which implied that BWI fraction did not act at the early stage of signal transduction pathway. CBP fraction induced differenciation of human leukemic cell line, HL-60 cells suggesting the carcinogenesis prevention of normal cell and possible induction of normalization for cancer cell.

• Korean Journal of Medicinal Crop Science
• /
• v.20 no.3
• /
• pp.153-158
• /
• 2012

In order to develop as a natural source of anticancer materials of Cudrania tricuspidata, the cytotoxicity of methanol extracts by harvesting parts and times against 8 cell lines including 293 (normal kidney cells) and A-431 (epidermoid carcinoma cells) were investigated using MTT assay. All harvesting parts had hardly cytotoxicity against 293. And methanol extracts of stem bark and root bark showed very high cytotoxicities against 7 cancer cell lines. The cytotoxicity was the highest against HeLa (cervix adenocarcinoma cells) and followed by MCF-7 (breast adenocarcinoma cells), AGS (stomach adenocarcinoma cells), HT-29 (colon adenocarcinoma cells), HepG2 (hepatoblastoma cells), A549 (lung carcinoma cells) and A-431. By the way, leaf extract had a cytotoxicity against only AGS and ripe fruit extract had no cytotoxicity. Among harvesting times, the cytotoxicity of root bark were high from April to September but that of stem bark showed a little difference. These results showed that anticancer activities of Cudrania tricuspidata extracts were eventful changes by harvesting parts and times.

• Korean Journal of Medicinal Crop Science
• /
• v.22 no.5
• /
• pp.369-377
• /
• 2014

In order to find out anticancer activity of Korean pepper (Capsicum annuum L.), the cytotoxicity against 8 cell lines including 293 (normal kidney cells) and A-431 (epidermoid carcinoma cells) of extracts by extraction solvents and plant parts were investigated using MTT assay. Also the correlation between content of capsaicin known as anticancer ingredient and cytotoxicity of extracts from pepper were analyzed. The distilled water extracts from seed and germinated seed showed very high cytotoxicity against 6 cancer cell lines including A549 (lung carcinoma cells), AGS (stomach adenocarcinoma cells), HeLa (cervix adenocarcinoma cells), HepG2 (hepatoblastoma cells), HT-29 (colon adenocarcinoma cells), and MCF-7 (breast adenocarcinoma cells). But 80% ethanol and methanol extracts showed cytotoxicity against 293 and AGS. The $RC_{50}$, that was, the concentration of sample required for 50% reduction of cell viability, of seed and germinated seed extracts against AGS were $33.4{\sim}389.1{\mu}g/m{\ell}$ and $63.9{\sim}1,316.7{\mu}g/m{\ell}$, respectively, so anticancer activity was higher in seed than in germinated seed. In capsaicin contents, seed with high cytotoxicity and pericarp with a little cytotoxicity contained $47.4{\sim}1,260.0{\mu}g/g$ and $58.3{\sim}1,498.0{\mu}g/g$, respectively. As these results, the correlation was not between cytotoxicity and capsaicin content.

• Nuclear Medicine and Molecular Imaging
• /
• v.41 no.3
• /
• pp.263-264
• /
• 2007

Splenic metastasis from colon carcinoma are rare and usually occur in the presence of disseminated visceral metastasis. The liver is the most common site of metastatic spread from colon cancer. Several hypotheses have attempted to explain the low incidence of splenic metastasis. It should be difficult for colorectal cancer cells to reach the spleen through the portal venous system, in which the blood flow is usually from the spleen to the liver. Reticuloendothelial system or rhythmic contraction of the spleen may squeeze out the tumor in the spleen. The absence of afferent lymphatic to the spleen, phagocytic activity and humoral anticancer substances are considered to be other reason for low incidence of splenic metastasis. We report the case of $^{18}F-FDG$ PET/CT finding in a 70-year-old woman who develop isolated splenic metastasis of sigmoid colon cancer.

• Journal of Korea Entertainment Industry Association
• /
• v.13 no.1
• /
• pp.217-223
• /
• 2019

Colon cancer is the most common form of cancer diagnosis in worldwide. There are growing interests in the health benefits associated with consumption of fruits and vegetables, especially for the prevention of cancer, cardiovascular or other chronic diseases. The objective of the present study was to investigate the antioxidant and anticancer activities of natural product, guarana(GR) and graviola(GV) in human colon carcinoma HCT-116 cells. MTT assay, flow cytometry analysis were employed to investigate the anticancer mechanism and DPPH assay was determined to the antioxidant activity to scavenge free radicals in extract of these. All two extracts showed significantly antioxidant activity at 50mg/ml of concentration. GR and GV reduced HCT-116 cell proliferation in a dose dependent manner. Specially GR treatment(96.65±3.71) also significantly increased the sub-G1 population more than GV(79.58±2.87) treatment in HCT-116 at the concentration of 10mg/ml, as shown by flow cytometry assay. Statistical analyses revealed GR and GV exhibited significantly high (P < 0.05) cytotoxicity in HCT-116. These findings indicate that GN and GV may serve as novel therapeutic agents for colon cancer treatment and future leads for drug development.

• Journal of Life Science
• /
• v.19 no.9
• /
• pp.1209-1217
• /
• 2009

Many cancer cells are sensitive to the TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. However, some cancer cells show either partial or complete resistance to TRAIL. Human colon carcinoma KM12 cells have been shown to be insensitive to TRAIL-induced apoptosis. To overcome TRAIL resistance in KM12 cells, we targeted key anti-apoptotic molecules involved in the modulation of TRAIL resistance in the cells, and evaluated the effects of quercetin as a TRAIL sensitizer in the cells. We found that quercetin acted in synergy with TRAIL to enhance TRAIL-induced apoptosis in KM12 cells by the down-regulation of c-FLIP and DNA-PKcs/Akt and up-regulation of death receptors (DR4/DR5), which led to the enhancement of TRAIL-mediated activation of caspases and subsequent cleavage of PARP, as well as up-regulation of Bax. These findings suggest that the DNA-PKcs/Akt signaling pathway, as well as c-FLIP, play essential roles in regulating cells in the escape from TRAIL-induced apoptosis. Based on these results, this study provides a potential application of quercetin in combination with TRAIL in the treatment of human colon cancer.

• Journal of Life Science
• /
• v.21 no.2
• /
• pp.194-201
• /
• 2011

Caudal-related homeodomain proteins play critical roles in intestine development and maintenance from Drosophila to humans. The loss or reduction of CDX1 and CDX2 are known to be associated with colon cancers. It has been well known that colorectal carcinogenesis is associated with serious oxidative stress and that catalase is decreased in colon carcinomas. However, the underlying molecular mechanisms remain elusive. Here, we report that Caudal-related homeodomain proteins positively regulate catalase expression in both Drosophila and humans. We found that Drosophila caudal heterozygotes have a decreased catalase expression and increased ROS generation in the hindgut, and that the overexpression of Caudal increases catalase promoter activity and catalase mRNA levels. We also found that CDX1 and CDX2 up-regulate catalase promoter activity and protein levels in HCT116 cells - human colorectal carcinoma cell lines. The level of catalase protein in several colorectal carcinoma cell lines was associated with CDX1 expression. These results suggest that CDX1 and CDX2 may be involved in intestinal homeostasis and tumorigenesis via regulation of catalase expression.

• Molecules and Cells
• /
• v.42 no.12
• /
• pp.869-883
• /
• 2019

Interleukin (IL)-15 is an essential immune-modulator with high potential for use in cancer treatment. Natural IL-15 has a low biological potency because of its short half-life and difficulties in mass-production. IL-15Rα, a member of the IL-15 receptor complex, is famous for its high affinity to IL-15 and its ability to lengthen the half-life of IL-15. We have double-transfected IL-15 and its truncated receptor IL-15Rα into CT26 colon cancer cells to target them for intracellular assembly. The secreted IL-15:IL-15Rα complexes were confirmed in ELISA and Co-IP experiments. IL-15:IL-15Rα secreting clones showed a higher anti-tumor effect than IL-15 secreting clones. Furthermore, we also evaluated the vaccine and therapeutic efficacy of the whole cancer-cell vaccine using mitomycin C (MMC)-treated IL-15:IL-15Rα secreting CT26 clones. Three sets of experiments were evaluated; (1) therapeutics, (2) vaccination, and (3) long-term protection. Wild-type CT26-bearing mice treated with a single dose of MMC-inactivated secreted IL-15:IL-15Rα clones prolonged survival compared to the control group. Survival of MMC-inactivated IL-15:IL-15Rα clone-vaccinated mice (without any further adjuvant) exceeded up to 100%. This protection effect even lasted for at least three months after the immunization. Secreted IL-15:IL-15Rα clones challenging trigger anti-tumor response via CD4⁺ T, CD8⁺ T, and natural killer (NK) cell-dependent cytotoxicity. Our result suggested that cell-based vaccine secreting IL-15:IL-15Rα, may offer the new tools for immunotherapy to treat cancer.

• Proceedings of the PSK Conference
• /
• 2003.04a
• /
• pp.148.2-149
• /
• 2003

The inhibitory effect of the lectins (KML-C) isolated from Korean mistletoe (KM; Viscum album coloratum), on tumor metastases produced by highly metastatic murine tumor cells, B 16-BL6 melanoma, colon 26-M3.1 carcinoma and L5178Y-ML25 lymphoma cells, was investigated in syngeneic mice. (omitted)