Characterization of the Immunoregulatory Action of Saikosaponin-d

Kato, Masashi; Pu, Mei-yi; Isobe, Ken‐ichi; Iwamoto, Takashi; Nagase, Fumihiko; Lwin, Tint; Zhang, Yuehua; Hattori, Taku; Yanagita, Noriyuki; Nakashima, Izumi

doi:10.1006/cimm.1994.1291

Cited by 52 publications

(42 citation statements)

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“…The immunoregulatory action of saikosaponin-d has been demonstrated by Kato et al (1994), who showed that saikosaponin-d uniquely modulates T lymphocyte function and that at least one target for the action of saikosaponin-d is located at, or before, the step of c-fos gene transcription, and following T-cell receptor/CD3-mediated protein tyrosine kinase activation. We have previously reported that the apoptotic e ect of curcumin, a plant phenol, may partly be mediated by a reduction in c-myc and bcl-2 mRNA expression (Chen & Huang, 1998).…”

Section: Discussionmentioning

confidence: 99%

Effect of saikosaponin, a triterpene saponin, on apoptosis in lymphocytes: association with c‐myc, p53, and bcl‐2 mRNA

Hsu

Cheng

Huang

2000

British J Pharmacology

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1 The mechanisms involved in the apoptotic e ect of saikosaponin-d, a triterpene saponin from Bupleurum falcatum L., were studied in human CEM lymphocytes and compared with those of dexamethasone (3610 77 M). 6 Levels of c-myc, p53, and bcl-2 mRNA were analysed by the reverse transcription-polymerase chain reaction. Levels of c-myc and p53 mRNA were signi®cantly increased, while the level of bcl-2 mRNA was decreased, by saikosaponin-d (10 75 M) treatment. Dexamethasone did not signi®cantly change the expression of these genes. 7 It is suggested that the apoptotic e ect of saikosaponin-d may be partly mediated by increases in c-myc and p53 mRNA levels accompanied by a decrease in bcl-2 mRNA level.

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Section: Discussionmentioning

confidence: 99%

Effect of saikosaponin, a triterpene saponin, on apoptosis in lymphocytes: association with c‐myc, p53, and bcl‐2 mRNA

Hsu

Cheng

Huang

2000

British J Pharmacology

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“…(a) The levels of Ret expression (a). The cell lysates (50 mg) from the skin and tumors at each stage were analysed by Western blotting, which was performed as described previously (Kato et al, 1994). Anti-Ret antibody was produced as described previously (Takahashi et al, 1993).…”

Section: D) Tumor Cells Were Stained For S-100 (E)mentioning

confidence: 99%

Transgenic mouse model for skin malignant melanoma

et al. 1998

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We report here on a novel metallothionein-I (MT)/ret transgenic mouse line in which skin melanosis, benign melanocytic tumor and malignant melanoma metastasizing to distant organs develop stepwise. The process of tumor development and its malignant transformation in this line may resemble that of the human giant congenital melanocytic nevus that is present at birth and that frequently gives rise to malignant melanoma during aging. We observed an increase in the expression level and activity of the ret transgene during the disease progression. That increase in transgene expression accompanied an activation of mitogen-activated protein kinases (MAPKs) and c-Jun as well as matrix metalloproteinases. These results suggest that progressive dysregulation of the expression level of the ret transgene might play a crucial role in the malignant transformation of melanocytic tumors developed in the MT/ret transgenic mouse line.

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“…We immunized 10-week-old nontransgenic BCF-1 mice and transgenic mice of lines 304, 192, and 242 with Ret protein, and examined the antigen (Ret)-dependent T-cell proliferation response in Figure 2 Time course of Ret protein expression in skin, thymus and brain from MT/ret transgenic mice of lines 304, 192, and 242. In (a) (line 304), (b) (line 192) and (c) (line 242), levels of Ret protein expression in indicated tissues (Sk, skin; Th, thymus; Br, brain) from the transgenic mice of dierent ages (F, fetus; N, newborn) were determined by Western blotting with anti-Ret antibody (Takahashi et al, 1993) according to the method described previously (Kato et al, 1994). In (d) autophosphorylation levels of Ret tyrosine kinase in the skin from the MT/ret transgenic mice of line 304 (0.0 ± 0.5 day-old), 192 (1.0 ± 1.5 dayold), and 242 (7.0 ± 7.5 day-old) were examined by immunoprecipitation with anti-Ret antibody followed by Western blotting with anti-phosphotyrosine antibody (D1; Transduction Laboratories, Lexington, KY, USA) or anti-Ret antibody (D2) vitro using a previously established method (Corradin et al, 1977;Dai et al, 1994).…”

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confidence: 99%

Linkage between melanocytic tumor development and early burst of Ret protein expression for tolerance induction in metallothionein-I/ret transgenic mouse lines

et al. 1999

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We examined the basis of the all or none dierence in inducing melanocytic tumor development among three transgenic mouse lines (304, 192 and 242) to which the same promoter-enhancer (metallothionein-I) and oncogene (ret) were introduced. We initially demonstrated that both skin melanosis and Ret protein expression in skin, thymus and brain ®rst became detectable before or immediately after birth in the mice of the tumor developing lines (304 and 192), whereas they became detectable a few days after birth in the mice of the nontumor developing line (242) by Western blotting and immunohistochemical analysis. Interestingly, the Ret protein expression in skin developed rapidly after birth as a burst with peak levels on 0.5 ± 1.5 day newborns of lines 304 and 192 and on 7.0 ± 7.5 day-old mice of line 242. The levels of autophosphorylation of Ret kinase in skin were, however, invariable among these three transgenic mouse lines. The mice of line 242, but not those of lines 192 and 304, responded to Ret protein immunization by increased antigen-dependent lymphocyte proliferation and T-cell-mediated tumor growth suppression in vitro. Furthermore, ret-transgenic mice of line 242, but not line 304, rejected the subcutaneously transplanted tumors that had originally developed in a mouse of line 304. These results suggest that whether oncogene product-speci®c-tolerance is established or not to antitumor immunity may be decided by the dynamics of ret oncogene expression before and after delivery and this is the primary factor determining development or non-development of melanoma.

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Characterization of the Immunoregulatory Action of Saikosaponin-d

Cited by 52 publications

References 0 publications

Effect of saikosaponin, a triterpene saponin, on apoptosis in lymphocytes: association with c‐myc, p53, and bcl‐2 mRNA

Effect of saikosaponin, a triterpene saponin, on apoptosis in lymphocytes: association with c‐myc, p53, and bcl‐2 mRNA

Transgenic mouse model for skin malignant melanoma

Linkage between melanocytic tumor development and early burst of Ret protein expression for tolerance induction in metallothionein-I/ret transgenic mouse lines

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