Cancer Research and Treatment

Review Article

Transcription Factors in the Cellular Signaling Network as Prime Targets of Chemopreventive Phytochemicals: Young-Joon Surh; Cancer Res Treat. 2004;36(5):275-286. Published online October 30, 2004; DOI: https://doi.org/10.4143/crt.2004.36.5.275

Accumulating evidence from epidemiologic and laboratory studies support an inverse relationship between a regular consumption of fruits and vegetables and the risk of specific cancers. Numerous phytochemicals derived from edible plants have been reported to possess ability to interfere with a specific stage of carcinogenic process. Multiple mechanisms have been proposed to account for the anti-carcinogenic actions of dietary constituents, but more attention has recently focussed on intracellular signaling cascades as common molecular targets of a wide variety of chemopreventive phytochemicals.

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Original Articles

Effect on Malignant Phenotype of Gastric Cancer Cell Line after p53 Gene Transduction: Sun Young Rha, Tae Soo Kim, Sook Jung Jeong, Joong Bae Ahn, kwang Yong Shim, Soo Jung Kong, Hwa Young Lee, Nae Choon Yoo, Jin Hyuk Choi, Ho Young Lim, Joo Young Lim, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim, Hyun Cheol Chung; J Korean Cancer Assoc. 1998;30(3):508-520.

Abstract PDF: PURPOSE
To evaluate the effect of wild type p53 gene transduction on the malignant phenotypes for metastasis in gastric cancer, we compared the biological phenpotypes of gastric cancer cell lines based on p53 gene status. Then, after retrovirus-mediated wild-type p53 gene transduction, we compared those phenotypes among parent YCC-3 cell line, vector transduced YCC-3v cell line and a clone of YCC-3C3. MATERIAL AND METHODS: Four human gastric cancer celi lines were used; YCC-l(mutant), YCC-2(wild), YCC-3(mutant) and AGS(wild). DNAs of the cell lines were analyzed to evaluate the mobility shift with PCR-SSCP. Tumorigenecity and proliferation were evaluated by soft agar assay and proliferation assay. Migratory capacity was measured by adhesion assay and Boyden chamber assay. p53 protein expression was measured by Western blot analysis and VEGF, WAF-1 were measured by ELISA assay. Angiogenic activity was measured by cross-feeding assay and cell cycle analysis was performed by flowcytometry. In vivo tumorigenicity was measured by xenograft in nude mice.
RESULTS
YCC-3 cell line with mutant p53 gene expressed all the phenotypes for the metastasis such as tumorigenicity, migration and angiogenesis. In a stable clone of YCC-3C3, no differences were found in proliferation, cell cycle and WAP-1 expression when compared to those of the control YCC-3v and parent YCC-3 cell line, even if increased p53 protein production was found by Western blot analysis. However, both in vitro and in vivo tumorigenicity were decreased in a stably transduced YCC-3C3 clone. The adhesive capacity was also decreased in YCC-3C3 clone whereas the endothelial cell growth stimulatory effect and VEGF production showed no difference compared to those of the YCC-3v cell line.
CONCLUSION
Wild-type p53 gene transduction in gastric cancer cell line decreased tumorigenicity which resulted from decreased colony forming activity and adhesive capacity but not formed changes of angiogenic activity. This suggested the possible application of anti- metastasis strategy with p53 gene therapy in gastric cancer.

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Alteration of Oleate-Phospholipase D Activities in Some Cell Lines after Irradiation: Chul Yong Kim, Myung Un Choi, Myung Sun Choi; J Korean Cancer Assoc. 1997;29(6):944-953.

Abstract PDF: PURPOSE
Phospholipase D (PLD) catalyzes the hydrolytic cleavage of terminal phosphate diester bond of glycerophopholipids to produce phosphatidic acid (PA). PLD plays an important role in signal transduction and is known to be involved closely in cancer promotion, inflammation, and other cell responses. In order to evaluate radiation effect in tumor cells, various cells were screened for PLD activities and examined their radiation effects on PLD following gamma- ray irradiation.
MATERIALS AND METHODS
PLD activities in 19 species of cell were measured by radioactive isotope method with 1,2 - di [1-14C] phosphatidylcholine in the presence of oleate. Among the cell lines examined, VERO 76, L 1210 and P 388 were selected and examined for their effects of metal ions and agonists on PLD activities before and after irradiation by Co-60 teletheraphy unit.
RESULTS
The activities of oleate-PLD were observed in 11 species among 19 cell lines examined. VERO 76 and L 1210 cells showed that the PLD activity increased immediately after irradiation and reached to 150~200% of the control levels. The activation of PLD in response to gamma-ray was maximum at 20 Gy. In irradiated VERO 76, the stimulatory effect of Mg2+ was reduced and the activation of PLD by agonists in irradiated cells vary from those of the control cells.
CONCLUSION
The activation effect of irradiation on PLD activity observed strongly implies that the PLD activity is closely related to the phenomena of cell necrosis. Therefore the cell lines examined here could provide a good source for the study of radiobiology that cover from cell death to cancer promotion.

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Comparison of Efficiency of Infection of Human Cancer Cell Lines Via Retroviral Vector System: Yeon Soo Kim, Hee Kyung Lim, Joo Hang Kim, Jin Sik Min; J Korean Cancer Assoc. 1997;29(1):1-10.

Abstract PDF: PURPOSE
There are several reasons why retroviruses are useful as vectors for gene therapy. However, retroviral vectors also have some limitations. Research in retroviral-mediated gene transfer has struggled with low titer and transduction efficiency on certain human target cells even with the addition of polycations to enhance transduction. Efficient in vivo gene transfer with retroviral vectors will require the availability of large amounts of vector at titers higher than generally possible by most current methods. Therefore, transduction efficiency of various human cell types with retroviral vector system is very important in human gene therapy. In an effort to test the transduction efficiency of a retrovial vector in the human cancer cell lines, a retroviral vector was infected into various human cancer cell lines.
MATERIALS AND METHODS
We generated retrovirus producing cell lines through transfection or infection of amphotropic packaging cell line PA317 with ecotropic retroviruses encoding bacterial lacZ gene. The amphotropic retrovirus vector was used to transduce various human cancer cell lines.
RESULTS
Of eight randomly chosen G418-resistant clones generated by transfection, only two clone produced the vector at up to >10 (6) cfu/ml, while one of five clones generated by infection yielded higher-titer virus in the absence of helper virus, up to 1 X 10 (7) cfu/ml, than the transfected clones. Transduction with supernatant derived from a PA317 producer cell line has resulted in transduction levels from 1% to 15%, 5- to 60-fold lower than those analyzed in NIH3T3 cells.
CONCLUSION
These findings suggest that new improved gene transfer method into human cancer cells using retroviruses is required for efficient in vivo cancer gene therapy.

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Correlation of PLC-γ1 Expression and DNA Ploidy Pattern in Hepatocellular Carcinomas: Sung Sook Kim, Soo Yeon Cho, Kyung Hee Kim, Jung Ran Kim, Young Han Lee, Pann Ghill Suh, Man Ha Huh, Young Hoon Park; J Korean Cancer Assoc. 1994;26(6):885-892.

Abstract PDF: Phospholipase C isozymes (PLCs) play a role in ligand-mediated signal transduction for cellu- lar activity such as proliferation and differentation. However, their biological significance of in carcinogenesis or tumor progression is not fully estabilished, although PLC-rl is known to be related to the cell growth or the oncogene. We examined the relative content of PLC-rl in human hepatocellular carcinoma (HCC) and the adjacent non tumorous liver tissue, by immunoperoxidase staining of paraffin embedded sections. Among 32 cases, 25 demonstrated s significant decrease of PLC-rl content in comparison to the adjacent nontumorous tissue. Seven cases revealed no remarkable change in PLC-rl expression. There was no HCC expressing higher level of PLC-rl. We also performed image cytometric studies to evaluate the relationship between the DNA ploidy pattern and the PLC-yl content. Interestingly, the tumors showing a decreased PLC-rl expression, were mostly diploid and tetraploid (except 3 cases) in contrast to those tumors showing no change in PLC-rl content which were exclusively aneuploid. The results suggest that PLC-rl expression is closely related to DNA ploidy of the tumor, and that there may be two different mechanisms of hepatocarcinogenesis: one is related to PLC-rl associated signal trasduction system, and the other is independent of PLC-rl.

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