• Natural Product Sciences
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• v.28 no.3
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• pp.115-120
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• 2022

Ten compounds, consisting of neoflavonoids (1-5), isoflavonoids (6 and 7), flavanone (8), and chalcones (9 and 10) were isolated from the ethyl acetate and n-butanol-soluble fractions of the heartwood of Dalbergia melanoxylon. The chemical structures were identified on the basis of spectroscopic evidence and compared to previously reported spectra. Compounds 1-10 were evaluated for cytotoxicity against HCT116 human colorectal cancer, MDA-MB-231 human metastatic breast cancer, and A2058 human melanoma cell lines. Among them, compounds 3 and 10 showed the strongest cytotoxic activity with IC₅₀ values of 11.92±1.07 μM, 10.83±1.02 μM, and 14.37±1.02 μM, 13.62±1.09 μM against HCT116 and MDA-MB-231 cell lines, respectively. Compounds 9 and 10 also had cytotoxic activity with IC₅₀ values of 13.49±1.18 μM and 9.82±0.91 μM against A2058 cell lines, respectively. To the best our knowledge, compounds 2 and 5-10 were isolated from this source for the first time.

• Biomedical Science Letters
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• v.23 no.3
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• pp.238-250
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• 2017

Patient's primary tumor-derived tumor cell lines likely represent ideal tools for human tumor biology in vitro and in vivo. Here, we describe eight human gastric carcinoma cell lines derived from established tumors in vivo upon subcutaneous transplantation of primary gastric carcinoma specimens in BALB/c nude mice. These xenografted gastric tumor cell lines (GTX) displayed close similarity with primary gastric tumor tissues in their in vivo growth pattern and genomic alterations. GTX-085 cells were resistant to cisplatin, while GTX-087 was the most sensitive cell line. GTX-085 was the only cell line showing a metastatic potential. Epithelial cell adhesion molecule (EPCAM) expression was especially strong in all tissue samples, as well as in cell cultures. GTX-139, the largest tumor graft obtained after injection, displayed distinct expression of CD44v6, fibroblast growth factor receptor 2 (FGFR2), and prominin 1 (PROM1, also known as CD133). In summary, we established eight xenograft gastric cancer cell lines from gastric cancer patient tissues, with their histological and molecular features consistent with those of the primary tumors. The established GTX cell lines will enable future studies of their responses to various treatments for gastric cancer.

• Molecules and Cells
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• v.45 no.5
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• pp.329-342
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• 2022

The liver is the predominant metastatic site for pancreatic cancer. However, the factors that determine the liver metastasis and the specific molecular mechanisms are still unclear. In this study, we used human pancreatic cancer cell line Hs766T to establish Hs766T-L3, a subline of Hs766T with stable liver metastatic ability. We performed RNA sequencing of Hs766T-L3 and its parental cell line Hs766T, and revealed huge differences in gene expression patterns and pathway activation between these two cell lines. We correlated the difference in pathway activation with the expression of the four core transcriptional factors including STAT1, NR2F2, GATA2, and SMAD4. Using the TCGA database, we examined the relative expression of these transcription factors (TFs) in pan-cancer and their relationship with the prognosis of the pancreatic cancer. Among these TFs, we considered GATA2 is closely involved in tumor metastasis and may serve as a potential metastatic driver. Further in vitro and in vivo experiments confirmed that GATA2-mediated transcriptional activation of Notch3 promotes the liver metastasis of Hs766T-L3, and knockdown of either GATA2 or Notch3 reduces the metastatic ability of Hs766T-L3. Therefore, we claim that GATA2 may serve as a metastatic driver of pancreatic cancer and a potential therapeutic target to treat liver metastasis of pancreatic cancer.

• Applied Microscopy
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• v.37 no.4
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• pp.239-248
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• 2007

Alteration of temperature is one of cancer therapies. In general, severe hyperthermia(around $43^{\circ}C$) and hypothermia(around $18^{\circ}C$) trigger apoptosis through mitochondria, though the specific mechanism is still unknown. CC-t6 and GB-d1 cell lines, which were originally derived from human cholangiocarcinoma and gall bladder cancer, were established from a metastatic lymph node. To investigate the mechanism of metastatic cancer cell response to thermal stresses, hyperthermia($37^{\circ}C{\rightarrow}43^{\circ}C$) and hypothermia($37^{\circ}C{\rightarrow}17.4^{\circ}C$) were designed. Thermal stresses did not induce apoptosis but necrotic cell death. Any alterations of caspase-3, -9, cytochrome c, Bax, and Bcl-2 were not found in both hyperthermia and hypothermia exposed fells using western blot analysis. In the transmission electron microscopy, typical necrotic, but not apoptotic, changes were observed. These results suggest that temperature changes induce cell death through necrotic pathway in metastatic cancer in vitro, and it can be one of effective anticancer methods.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3751-3755
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• 2012

Aim: Tea polyphenols are known to play roles in critical steps of human lung carcinoma cell metastasis. For understanding the mechanisms whereby they inhibit tumor metastasis, the present study was conducted to investigate their effects on the adhesion of highly metastatic lung carcinoma cell lines (PG cells) to endothelial cells (EC cells) and adhesion molecule expression in vitro. Methods: The expression of CD44 or CD54 in the PG cells was detected by flow cytometry and adhesion of PG cells to EC cells was assessed by confocal microscopy double fluorescence staining. Results: The results showed that tea polyphenols: (1) inhibited the expression of CD44 and CD54, two important adhesion molecules in the PG cells in a dose-dependent manner; (2) significantly blocked the adhesion of PG cells to EC cells not only in a state of rest but also when active; and (3) influenced CD44 and CD54 expression during the adhesion process of PG cells to EC cells. Conclusions: The data indicated that the blocking role of tea polyphenols in the adhesion of PG cells to EC cells is related to CD44 and CD54. The mechanism of tea polyphenol prevention of human lung carcinoma metastasis might be through inhibiting adhesion molecule expression to block cancer cell adhesion.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3667-3671
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• 2015

Invasion and metastasis is the major cause of tumor recurrence, difficulty for cure and low survival rate. Excavating key transcription factors, which can regulate tumor invasion and metastasis, are crucial to the development of therapeutic strategies for cancers. PU.1 is a master hematopoietic transcription factor and a vital regulator in life. Here, we report that, compared to adjacent non-cancerous tissues, expression of PU.1 mRNA in metastatic hepatocellular carcinoma (HCC), but not primary HCC, was significantly down-regulated. In addition, levels of PU.1 mRNA in metastatic hepatoma cell lines MHCC97L and MHCC97H were much lower than in non-metastatic Hep3B cells. Transwell invasion assays after PU.1 siRNA transfection showed that the invasion of hepatoma cell lines was increased markedly by PU.1 knockdown. Oppositely, overexpression of PU.1 suppressed the invasion of these cells. However, knockdown and overexpression of PU.1 did not influence proliferation. Finally, we tried to explore the potential mechanism of PU.1 suppressing hepatoma cell invasion. ChIP-qPCR analysis showed that PU.1 exhibited a high binding capacity with miR-615-5p promoter sequence. Overexpression of PU.1 caused a dramatic increase of pri-, pre- and mature miR-615-5p, as well as a marked decrease of miR-615-5p target gene IGF2. These data indicate that PU.1 inhibits invasion of human HCC through promoting miR-615-5p and suppressing IGF2. These findings improve our understanding of PU.1 regulatory roles and provided a potential target for metastatic HCC diagnosis and therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.6963-6966
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• 2015

Background: During the past few years, Hesa-A, a herbal-marine mixture, has been used to treat cancer as an alternative medicine in Iran. Based on a series of studies, it is speculated that Hesa-A possesses special cytotoxic effects on invasive tumors. To test this hypothesis, we investigated the selective anticancer effects of Hesa-A on several cancer cell lines with different metastatic potential. Materials and Methods: Hesa-A was prepared in normal saline as a stock solution of 10 mg/ml and further diluted to final concentrations of $100{\mu}/ml$, $200{\mu}g/ml$, $300{\mu}g/ml$ and $400{\mu}g/ml$. MTT-based cytotoxicity assays were performed with A549 (lung non small cancer), MCF-7 (breast adenocarcinoma), SKOV3 (ovarian cancer), and PC-3 (prostate adenocarcinoma) cells. Results: All treated cancer cells showed significant (P<0.01) or very significant (P<0.0001) differences in comparison to negative control at almost all of the tested doses ($100-400{\mu}g/ml$). At the lower dose ($100{\mu}g/ml$), Hesa-A reduced cell viability to 66%, 45.3%, 35.5%, 33.2% in SKOV3, A549, PC-3 and MCF-7 cells, respectively. Moreover, at the highest dose ($400{\mu}g/ml$), Hesa-A resulted in 88.5%, 86.6%, 84.9% and 79.3% growth inhibition in A549, MCF-7, PC-3 and SKOV3 cells, respectively. Conclusions: Hesa-A exert potent cytotoxic effects on different human cancer cells, especially those with a high metastatic potential.

• The Korea Genome Conference
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• 2004.07a
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• pp.50.1-50.1
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• 2004

• Proceedings of the PSK Conference
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• 2002.04a
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• pp.165.1-165.1
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• 2002

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.3
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• pp.765-770
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• 2003

To explore the possible cancer agent from oriental prescriptions, we have examined its antitumor and anti metastatic activities of Kamibojungikgi-tang(KBIT). KBIT extracts exhibited cytotoxicity against P388, A549 and B16-F10 cell lines in a dose-dependent manner and showed antiadhesive effect of A549 cell to complex extracellular matrix at 1 ㎎/㎖ in vitro. In DNA topoisomerase I assay, KBIT extracts showed strong inhibitoty effect in a dose-dependent manner. In pulmonary colonization assay with B16BL6, a number of colonies in the lungs were decreased effectively in KBIT treated group as compared with control group. Moreover, in CAM assay, KBIT extracts significantly inhibited angiogenesis at 15㎍/egg as compared with control. The T/C% was 141% in KBIT treated group in S-180 bearing ICR mice. From the above results it was concluded that KBIT had antitumor and anti metastatic activities. So it is expected to be clinically helpful on the prevention and treatment of cancer, although it is still necessary to study its mechanism on molecular biology and immunology.