Novel suppressive effects of cardamonin on the activity and expression of transglutaminase-2 lead to blocking the migration and invasion of cancer cells

Park, Mi Kyung; Jo, Seongil; Lee, Hye Ja; Kang, June Hee; Kim, You Ri; Kim, Hyun Ji; Lee, Eun Ji; Koh, Jun Seok; Ahn, Kyung Ok; Jung, Kyung Chae; Oh, Seung Hyun; Kim, Soo Youl; Lee, Chang Hoon

doi:10.1016/j.lfs.2012.11.009

Cited by 27 publications

(31 citation statements)

References 34 publications

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“…24) Additionally, Park et al recently found that cardamonin inhibits the invasion of cancer cells by suppressing transglutaminase-2 expression and inhibiting its activity. 25) In this study, we demonstrated, for the first time, that cardamonin suppresses the proliferation of colon cancer cells by promoting the degradation of intracellular β-catenin, which is abnormally accumulated in colon cancer cells.…”

Section: Discussionmentioning

confidence: 71%

Cardamonin Suppresses the Proliferation of Colon Cancer Cells by Promoting β-Catenin Degradation

Park

Gwak

Han

et al. 2013

Biological & Pharmaceutical Bulletin

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Aberrant accumulation of intracellular β-catenin and subsequent activation of β-catenin response transcription (CRT) in intestinal epithelial cells is a frequent early event during the development of colon cancer. Here we show that cardamonin, a chalcone isolated from Aplinia katsumadai Hayata, inhibited CRT in SW480 colon cancer cells that carry inactivating mutation in the adenomatous polyposis coli (APC) gene. Cardamonin also down-regulated intracellular β-catenin levels in SW480 cells without affecting its mRNA levels. Interestingly, pharmacological inhibition of the proteasome prevented the cardamonin-induced downregulation of β-catenin. In addition, cardamonin suppressed the expression of cyclin D1 and c-myc, which are known β-catenin/T cell factor (TCF)-dependent genes. Moreover, cardamonin inhibited the growth of various colon cancer cells and induced G2/M cell cycle arrest in SW480 colon cancer cells. These findings indicate that cardamonin is a potential chemotherapeutic agent against colon cancer.

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Section: Discussionmentioning

confidence: 71%

Cardamonin Suppresses the Proliferation of Colon Cancer Cells by Promoting β-Catenin Degradation

Park

Gwak

Han

et al. 2013

Biological & Pharmaceutical Bulletin

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“…Three essential amino acid residues including Lys-591, Arg-609, and Ser-613 were identified to form hydrogen bond between STAT3 and cardamonin. Previous study has shown STA-21, which was selected from 429,000 compounds by computational screening also interacts with STAT3 directly [21]. However, the binding site in STAT3 of STA-21 includes the amino acid residues, Arg609, Arg595, and Ile635.…”

Section: Discussionmentioning

confidence: 99%

“…Mechanically, Leu-706, Thr-708, and Phe-710 bind to a cavity on the SH2 domain of the other monomer, in combination with phosphorylated Tyr-705 [21]. Small molecules specifically binding to this cavity are supposed to block STAT3 dimerization by competing with the amino acid residues.…”

Section: Cardamonin Directly Interacts With Stat3 By Docking Analysismentioning

confidence: 99%

“…Recent studies revealed that cardamonin not only possesses anti-inflammation activity, but also suppresses the proliferation of human tumor cells, including myeloma and colorectal carcinoma [16][17][18][19]. However, the mechanism underlying the inhibition effects of cardamonin on the cancer cells is not well documented, although inhibition of mTOR, Tgase-2, and NF-kB may be associated with its bioactivity [20][21][22]. In the present study, we investigated the effects of cardamonin on the self-renewal and cell apoptosis in GSCs and its association with STAT3 pathway.…”

Section: Introductionmentioning

confidence: 99%

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Cardamonin induces apoptosis by suppressing STAT3 signaling pathway in glioblastoma stem cells

Liu

Zhao

et al. 2015

Tumor Biol.

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Glioblastoma stem cells (GSCs) are the initiating cells in glioblastoma multiforme (GBM) and contribute to the resistance of GBM to chemotherapy and radiation. In the present study, we investigated the effects of cardamonin (3,4,2,4-tetrahydroxychalcone) on the self-renewal and apoptosis of GSCs, and if its action is associated with signal transducer and activator of transcription 3 (STAT3) pathway. CD133(+) GSCs, a kind of GSCs line, was established from human glioblastoma tissues. Cardamonin inhibited the proliferation and induced apoptosis in CD133+ GSCs. The proapoptotic effects of temozolomide (TMZ) were further enhanced by cardamonin in CD133+ GSCs and U87 cells in vitro. For in vivo study, injection of 5 × 10(5) cells of CD133+ GSCs subcutaneously (s.c.) into nude mice, 100 % of large tumors were developed within 8 weeks in all mice; in contrast, only one out of five mice developed a small tumor when 5 × 10(5) cells of CD133(-) GMBs cells were injected. Cardamonin also inhibited STAT3 activation by luciferase assay and suppressed the expression of the downstream genes of STAT3, such as Bcl-XL, Bcl-2, Mcl-1, survivin, and VEGF. Furthermore, cardamonin locked nuclear translocation and dimerization of STAT3 in CD133(+) GSCs. Docking analysis confirmed that cardamonin molecule was successfully docked into the active sites of STAT3 with a highly favorable binding energy of -10.78 kcal/mol. The study provides evidence that cardamonin is a novel inhibitor of STAT3 and has the potential to be developed as a new anticancer agent targeting GSCs. This study also reveals that targeting STAT3 signal pathway is an important strategy for the treatment of human GBM.

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“…The cells that failed to pass through the filters were removed by scrubbing with cotton swabs after 24 h (invasion assay). The cells on the undersurface were fixed in methanol and stained with 0.5% Crystal Violet (Beijing Chemical works, Beijing, China), then images were captured and the cells were quantified in 10 random fields per membrane (13). …”

Section: Methodsmentioning

confidence: 99%

A novel taspine derivative suppresses human liver tumor growth and invasion in vitro and in vivo

et al. 2013

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Taspine is an attractive target of research due to the anticancer and anti-angiogenic effects shown by in vitro and in vivo experiments. The present study investigated the role of tas1611, which is a derivative of taspine that has increased activity and solubility, in the regulation of the invasive properties of the SMMC-7721 liver cell line in vitro and in tumor inhibition in vivo. The proliferation of the SMMC-7721 cells was examined using the tetrazole blue colorimetric method. Matrigel® invasion chamber assays and zymogram analyses were performed to assess the inhibitory effect of tas1611 on cell invasion. Finally, a solid tumor athymic mouse model was employed to further investigate the anti-tumor effect of this compound. The results revealed that tas1611 had a marked inhibitory effect on the invasion of the SMMC-7721 cells and that this effect was associated with the activity and expression levels of matrix metalloproteinase (MMP)-2 and MMP-9. Furthermore, tas1611 was able to inhibit tumor growth effectively in a solid tumor SMMC-7721 athymic mouse model. In conclusion, tas1611 may serve as a promising novel therapeutic candidate for the treatment of metastatic liver cancer.

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Novel suppressive effects of cardamonin on the activity and expression of transglutaminase-2 lead to blocking the migration and invasion of cancer cells

Cited by 27 publications

References 34 publications

Cardamonin Suppresses the Proliferation of Colon Cancer Cells by Promoting β-Catenin Degradation

Cardamonin Suppresses the Proliferation of Colon Cancer Cells by Promoting β-Catenin Degradation

Cardamonin induces apoptosis by suppressing STAT3 signaling pathway in glioblastoma stem cells

A novel taspine derivative suppresses human liver tumor growth and invasion in vitro and in vivo

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