Expression of the Anti-metastatic Effect Induced by Juzen-taiho-to is Based on the Content of Shimotsu-to Constituents.

Onishi, Yuki; Yamaura, Takeshi; Tauchi, Katsunori; Shimoyama, Takashi; Tsukada, Kazuhiro; Nunome, Shinyu; Komatsu, Yasuhiro; Saiki, Ikuo

doi:10.1248/bpb.21.761

Cited by 52 publications

(29 citation statements)

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“…On the other hand, Keishibukuryogan has been shown to suppress renal fibrosis, which is caused by TGF-β-induced EMT (17). Despite the inhibitory activity of CC extract, the possibility can not be excluded that other herbal medicines might play a role in concert with CC extract, because of the harmonization effects among various herbal medicines (11,12).…”

Section: Discussionmentioning

confidence: 99%

“…Our previous studies showed that Juzentaihoto, a Japanese Kampo medicine, prevents metastasis in mouse models (10)(11)(12). Because Juzentaihoto contains ten ('Ju' means 'ten' in Japanese) kinds of herbal ingredients, we thus investigated whether each component can suppress TGF-β-induced EMT.…”

Section: Cinnamomi Cortex (Cc) Extract Suppresses Tgf-β-induced Emtmentioning

confidence: 99%

“…Interestingly, our previous studies showed that Juzentaihoto indirectly inhibited cancer metastasis through the activation of macrophages and T cells in mouse models (10)(11)(12). Although Juzentaihoto could suppress cancer metastasis, it is not well known how Juzentaihoto can directly affect tumor cells during the metastasis process and which herbal ingredients of Juzentaihoto are involved in the regulation of EMT.…”

Section: Introductionmentioning

confidence: 99%

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Procyanidin C1 from Cinnamomi Cortex inhibits TGF-β-induced epithelial-to-mesenchymal transition in the A549 lung cancer cell line

Kin

Kato

Kaneto

et al. 2013

International Journal of Oncology

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Abstract. Cancer metastasis is one of the most critical events in cancer patients, and the median overall survival of stage IIIb or IV patients with metastatic lung cancer in the TNM classification is only 8 or 5 months, respectively. We previously demonstrated that Juzentaihoto, a Japanese traditional medicine, can inhibit cancer metastasis through the activation of macrophages and T cells in mouse cancer metastatic models; however, the mechanism(s) through which Juzentaihoto directly affects tumor cells during the metastasis process and which herbal components from Juzentaihoto inhibit the metastatic potential have not been elucidated. In this study, we focused on the epithelial-to-mesenchymal transition (EMT), which plays an important role in the formation of cancer metastasis. We newly determined that only the Cinnamomi Cortex (CC) extract, one of 10 herbal components of Juzentaihoto, inhibits TGF-β-induced EMT. Moreover, the contents of catechin trimer in CC extracts were significantly correlated with the efficacy of inhibiting TGF-β-induced EMT. Finally, the structure of the catechin trimer from CC extract was chemically identified as procyanidin C1 and the compound showed inhibitory activity against TGF-β-induced EMT. This illustrates that procyanidin C1 is the main active compound in the CC extract responsible for EMT inhibition and that procyanidin C1 could be useful as a lead compound to develop inhibitors of cancer metastasis and other diseases related to EMT.

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Section: Discussionmentioning

confidence: 99%

Section: Cinnamomi Cortex (Cc) Extract Suppresses Tgf-β-induced Emtmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Procyanidin C1 from Cinnamomi Cortex inhibits TGF-β-induced epithelial-to-mesenchymal transition in the A549 lung cancer cell line

Kin

Kato

Kaneto

et al. 2013

International Journal of Oncology

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“…On the other hand, TJ-41 has recently been reported to activate macrophages and natural killer (NK) cells (13)(14)(15). Moreover, some studies have demonstrated that TJ-41 inhibits experimental liver metastasis (16) and also exerts an anti-neoplastic effect in several kinds of malignant tumors, including skin cancer, hepatoma, ovarian cancer, and uterine cancer (17)(18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

Chemopreventative Effect of Hochu-ekki-to (TJ-41) on Chemically Induced Biliary Carcinogenesis in Hamsters

Tsuneoka

Tajima

Kitasato

et al. 2009

Journal of Surgical Research

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“…[6][7][8][9] Among them, Juzen-taiho-to reduces liver metastasis by colon 26-L5 carcinoma cells as well as pulmonary metastasis by B16-BL6 melanoma cells, and its antimetastatic effect appears likely to be mediated by the activation of macrophages and/or T cells in the host immune system. 7) Keishi-ka-kei-to is also able to inhibit the pulmonary metastasis of B16 melanoma cells and its effect is in part due to the stimulation of CD8 ϩ T cells. 6) Shosaiko-to suppresses pulmonary metastasis induced by Lewis lung carcinoma cells, and the enhanced number of peritoneal macrophages and elevated binding of C3 cleavage products to macrophages after Shosaiko-to treatment may be related to its antimetastatic effects.…”

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confidence: 99%

Suppressive Effect of Shichimotsu-koka-to (Kampo Medicine) on Pulmonary Metastasis of B16 Melanoma Cells.

Ohno

Ogihara

2002

Biological & Pharmaceutical Bulletin

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The lung, as well as the liver, is one of the organs most frequently involved in metastatic deposits from primary tumors.1-3) Tumor cell metastasis is a complex, multistep process that involves cell separation from the primary tumor, entry into the vascular and lymphatic systems, transport to and arrest within the microcirculation of distant organs, and extravasation. 4,5) The emergence of metastasis in organs distant from the primary tumor is the most devastating aspect of cancer. From this point of view, various inhibitors, such as inhibitors of angiogenesis and matrix metalloproteinase, are presently being developed as novel therapeutic drugs.Several Kampo medicines, such as Keishi-ka-kei-to, Juzen-taiho-to, Shimotsu-to, Unsei-in, Hochu-ekki-to, and Shosaiko-to have been so far reported to exhibit an antimetastatic effect.6-9) Among them, Juzen-taiho-to reduces liver metastasis by colon 26-L5 carcinoma cells as well as pulmonary metastasis by B16-BL6 melanoma cells, and its antimetastatic effect appears likely to be mediated by the activation of macrophages and/or T cells in the host immune system. 7) Keishi-ka-kei-to is also able to inhibit the pulmonary metastasis of B16 melanoma cells and its effect is in part due to the stimulation of CD8 ϩ T cells. 6) Shosaiko-to suppresses pulmonary metastasis induced by Lewis lung carcinoma cells, and the enhanced number of peritoneal macrophages and elevated binding of C3 cleavage products to macrophages after Shosaiko-to treatment may be related to its antimetastatic effects. 9) However, there have been few studies of Kampo medicines in the metastatic setting.Shichimotsu-koka-to (SKT), which is used to treat hypertension, especially essential and renal hypertension, and atherosclerosis, consists of seven medicinal plants (Paeoniae Radix, Angelicae Radix, Astragali Radix, Rehmanniae Radix, Cnidii Rhizoma, Phellodendri Cortex, and Uncariae Uncus et Ramulus), some of which have been studied to clarify their pharmacological actions. SKT shares four medicinal plants (Rehmanniae radix, Paeoniae radix, Cnidii rhizoma, Angelicae radix) with Shimotsu-to and Unsei-in, which exhibit antimetastatic effects against colon26-L5 carcinoma cells-induced liver metastasis. In addition, SKT shares five medicinal plants (Astragali Radix, Rehmanniae Radix, Paeoniae Radix, Cnidii Rhizoma, Angelicae Radix) with Juzentaiho-to, which also has antimetastatic effects. However, in addition to its antimetastatic effect, the pharmacological and biological actions of SKT have not been thoroughly investigated to date. A few reports found that SKT decreases systolic blood pressure and attenuates glomerular sclerotic lesions in the kidney after 4 weeks of treatment in salt-induced hypertensive Dahl strain rats, 10) and shows radical scavenging activity by increasing superoxide dismutase activity and decreasing xanthine oxidase activity in the brain. 11) SKT is able to quench superoxide anion as determined by electronspin resonance analysis in vitro. Considering that reactive oxygen species play an agg...

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Expression of the Anti-metastatic Effect Induced by Juzen-taiho-to is Based on the Content of Shimotsu-to Constituents.

Cited by 52 publications

References 0 publications

Procyanidin C1 from Cinnamomi Cortex inhibits TGF-β-induced epithelial-to-mesenchymal transition in the A549 lung cancer cell line

Procyanidin C1 from Cinnamomi Cortex inhibits TGF-β-induced epithelial-to-mesenchymal transition in the A549 lung cancer cell line

Chemopreventative Effect of Hochu-ekki-to (TJ-41) on Chemically Induced Biliary Carcinogenesis in Hamsters

Suppressive Effect of Shichimotsu-koka-to (Kampo Medicine) on Pulmonary Metastasis of B16 Melanoma Cells.

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