Müllerian inhibiting substance inhibits an ovarian cancer cell line via β-catenin interacting protein deregulation of the Wnt signal pathway

Park, Sang Ho; Chung, Youn‐Jee; Song, Jae Yen; Kim, Sang Il; Pépin, David; MacLaughlin, David T.; Donahoe, Patricia K.; Kim, Jang Heub

doi:10.3892/ijo.2017.3874

Cited by 16 publications

(15 citation statements)

References 30 publications

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“…We believe that the slight pro‐rAMH activity is due to the presence of a small amount (up to 5%) of half‐cleaved rAMH in the preparation. Note that the biological activity of purified C ‐rAMH was comparable with that of the heterogeneous preparation of full‐length rAMH previously obtained in a more complicated way in other studies (Lorenzo et al, ; Park et al, ). Our results indicate the feasibility of C ‐rAMH‐based antitumor drugs development.…”

Section: Resultssupporting

confidence: 81%

Purification of human recombinant anti‐mullerian hormone and its derivatives

Rak

Трофимов

Pigareva

et al. 2020

Biomedical Chromatography

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Anti-mullerian hormone (AMH) is a cytokine of transforming growth factor β (TGF-β) superfamily able to induce apoptosis in cells bearing specific AMH type II receptors (AMHRII). AMHRII is overexpressed in some malignant cells, so at present recombinant AMH (rAMH) is considered as a new candidate antineoplastic drug. The use of rAMH may be especially effective in case of such severe diseases as ovarian, prostate and breast cancer. However, the development of a new drug is hampered by the laboriousness of obtaining highly purified rAMH and by the lack of data about the pharmacological characteristics of rAMH derivatives. In this work, we obtained preparations of prohormone, half-cleaved rAMH and a C-terminal fragment of rAMH, which was confirmed by qualitative and quantitative analyses. To obtain rAMH and its derivatives we used a previously developed highly effective producer strain containing the optimized human AMH gene. The production process has been divided into several stages: (a) rAMH biosynthesis in the bioreactor; (b) culture media preparation; (c) purification of rAMH and its derivatives using immunoaffinity chromatography and reversed-phase HPLC; (d) identification of the purified proteins by immunoblotting and analytical reversed-phase HPLC; and (e) evaluation of the hormone forms activity. The obtained proteins may be used in preclinical trials and in vitro study of rAMH derivatives properties.

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Section: Resultssupporting

confidence: 81%

Purification of human recombinant anti‐mullerian hormone and its derivatives

Rak

Трофимов

Pigareva

et al. 2020

Biomedical Chromatography

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“…The same product, purchased from alternative companies, will be used in future studies. Finally, the working concentration of rhAMH was diluted to 10 µg/ml according to previous experiments (30,31). It would have been ideal to instead perform a dose-response analysis to identify the optimal working concentration.…”

Section: Discussionmentioning

confidence: 99%

Anti‑M�llerian hormone inhibits proliferation and induces apoptosis in epithelial ovarian cancer cells by regulating the cell cycle and decreasing the secretion of stem cell factor

Zhang

Deng²,

Xiong

et al. 2018

Oncol Lett

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Anti-Müllerian hormone (AMH) has been demonstrated to exhibit an inhibitory effect on the proliferation, invasion, metastasis and drug resistance of ovarian cancer. However, the mechanisms underlying these effects remain unclear. In the present study, 10 µg/ml recombinant human AMH (rhAMH) was administered to human OVCAR3 and OVCAR8 epithelial ovarian cancer (EOC) cell lines. Cell proliferation, apoptosis and cell cycle were analyzed. The level of stem cell factor (SCF) was detected using a reverse transcription-quantitative polymerase chain reaction and an ELISA, respectively. The exogenous addition of rhAMH significantly reduced the proliferation of OVCAR3 and OVCAR8 cell lines compared with the control group (P<0.01). The apoptosis rate in the rhAMH treated group (48 h) significantly increased compared with in the control group (OVCAR3, P=0.035; OVCAR8, P=0.020). The apoptosis rate increased at 72 h but did not exhibit a significant difference when compared with the 48 h group (OVCAR3, P=0.145; OVCAR8, P=0.296). The percentage of cells in the G phase in the rhAMH treated group (48 h) increased but was not significantly different compared with the control group (OVCAR3, P=0.070; OVCAR8, P=0.051). However, there was a significant difference at 72 h compared with the control group (OVCAR3, P=0.016; OVCAR8, P=0.019). At 48 h, the rhAMH-treated group exhibited a statistically significant inhibition of SCF mRNA expression levels (P=0.008), but no significant difference in the protein expression levels (P=0.101) compared with the control, though a significant inhibition was exhibited at 72 h (mRNA expression levels, P=0.005; protein expression levels, P=0.036). The present study revealed that rhAMH may be able to inhibit the proliferation and induce the apoptosis of EOC cells via G/S-phase cell cycle arrest and the decreased secretion of SCF.

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“…Since most gynecologic tumors originate from Müllerian duct derived tissues and MIS/AMH causes regression of the Müllerian duct, it is expected to inhibit the growth of the gynecologic tumors via MIS/AMH receptor-mediated mechanism [ 3 11 ]. Furthermore, several lines of evidence suggest that MIS/AMH inhibits proliferation in tissues and cell lines of MIS/AMH receptor-expressing gynecologic malignancies such as ovarian cancer [ 12 13 14 15 16 17 ], cervical cancer [ 18 19 20 21 ], and endometrial cancer [ 22 23 ]. In vitro studies using human epithelial ovarian cancer cell line (OVCAR 8) revealed that MIS/AMH inhibits growth of epithelial ovarian cancer cells [ 14 17 ].…”

Section: Discussionmentioning

confidence: 99%

“…MIS/AMH not only plays an important role in fetal sexual development, but also inhibits growth of tumors originating from the Müllerian duct where the MIS/AMH receptor is expressed [ 9 10 11 ], such as ovarian [ 12 13 14 15 16 17 ], cervical [ 18 19 20 21 ], and endometrial cancers [ 22 23 ]. Masiakos et al [ 14 ] reported that MIS/anti-Müllerian hormone type II receptor (AMHRII) is expressed at a high frequency in cells detected in ascites of patients with stage III/IV ovarian cancer, and MIS/AMH cause the growth inhibition of ovarian cancer cells expressing the MIS/AMH receptor.…”

Section: Introductionmentioning

confidence: 99%

The expression of Müllerian inhibiting substance/anti-Müllerian hormone type II receptor in myoma and adenomyosis

et al. 2018

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ObjectiveWe compared the expression levels of Müllerian inhibiting substance (MIS)/anti-Müllerian hormone type II receptor (AMHRII) in uterine myoma and adenomyosis to evaluate the possibility of using MIS/anti-Müllerian hormone (AMH) as a biological regulator or therapeutic agent in patients with uterine leiomyoma and adenomyosis.MethodsWe studied normal uterine myometrium, leiomyoma, endometrial tissue, and adenomyosis from 57 patients who underwent hysterectomy for uterine leiomyoma (22 cases) or adenomyosis (28 cases) and myomectomy for uterine myoma (7 cases). Immunohistochemical staining was used to confirm the MIS/AMHRII protein expression level in each tissue. Reverse transcription-polymerase chain reaction was performed to quantify MIS/AMHRII mRNA expression.ResultsThe MIS/AMHRII protein was more strongly expressed in uterine myoma (frequency of MIS/AMHRII expressing cells: 51.95%±13.96%) and adenomyosis (64.65%±4.85%) tissues than that in the normal uterine myometrium (3.15%±1.69%) and endometrium (31.10%±7.19%). In the quantitative analysis of MIS/AMHRII mRNA expression, MIS/AMHRII mRNA expression levels in uterine myoma (mean density: 4.51±0.26) and adenomyosis (6.84±0.20) tissues were higher than that in normal uterine myometrial tissue (0.08±0.09) and endometrial tissue (1.63±0.06).ConclusionThis study demonstrated that MIS/AMHRII was highly and strongly expressed on uterine myoma and adenomyosis. Our data suggest that MIS/AMH may be evaluated as a biological modulator or therapeutic agent on MIS/AMHRII expressing uterine myoma and adenomyosis.

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Müllerian inhibiting substance inhibits an ovarian cancer cell line via β-catenin interacting protein deregulation of the Wnt signal pathway

Cited by 16 publications

References 30 publications

Purification of human recombinant anti‐mullerian hormone and its derivatives

Purification of human recombinant anti‐mullerian hormone and its derivatives

Anti‑M�llerian hormone inhibits proliferation and induces apoptosis in epithelial ovarian cancer cells by regulating the cell cycle and decreasing the secretion of stem cell factor

The expression of Müllerian inhibiting substance/anti-Müllerian hormone type II receptor in myoma and adenomyosis

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