Human MutT Homolog 1 (MTH1) Inhibitor Reduces the Biological Activity of Ovarian Carcinoma Cells

This study intends to discuss the mechanism of MTH1 inhibitor (TH588) in the biological activity of ovarian carcinoma cells. A2780 and SKOV-3 cells were treated with different concentrations of TH588 and assigned into AT group (control), BT group (8 μmol/L TH588), CT group (16 μmol/L), DT group (32 μmol/L), ET group (64 μmol/L) and FT group (128 μmol/L) followed by measuring level of Bcl-2 and Bax by Western blot and PCR, and cell biological activities by MTT, FCM and Transwell chamber assay. The cell proliferative rate was not affected in AT group, but was lower in other groups in a reverse dose-dependent manner. There was significant difference on apoptotic rate and cell invasion among groups with increased apoptosis and reduce invasion after TH588 treatment. FT group showed lowest expression of Bcl-2 and Bax compared to other groups. In conclusion, the biological activity of A2780/SKOV3 cells could be reduced by MTH1 inhibitor which was probably through regulation of Bax and Bcl-2 expression.

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The Inhibitory Effect of Ellagic Acid on Cell Growth of Ovarian Carcinoma Cells

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/306705 ◽

2013 ◽

Vol 2013 ◽

pp. 1-12 ◽

Cited By ~ 24

Author(s):

Yuan-Chiang Chung ◽

Li-Cheng Lu ◽

Ming-Hsiu Tsai ◽

Yu-Jen Chen ◽

Yi-Ying Chen ◽

...

Keyword(s):

Cell Cycle ◽

Ovarian Carcinoma ◽

Cell Lines ◽

Ellagic Acid ◽

Molecular Mechanisms ◽

Inhibitory Effect ◽

Carcinoma Cells ◽

Dependent Manner ◽

Ovarian Carcinoma Cells ◽

Human Ovarian Carcinoma

Ellagic acid (EA) is able to inhibit the growth of several cancer cells; however, its effect on human ovarian carcinoma cells has not yet been investigated. Ovarian carcinoma ES-2 and PA-1 cells were treated with EA (10~100 μM) and assessed for viability, cell cycle, apoptosis, anoikis, autophagy, and chemosensitivity to doxorubicin and their molecular mechanisms. EA inhibited cell proliferation in a dose- and time-dependent manner by arresting both cell lines at the G1 phase of the cell cycle, which were from elevating p53 and Cip1/p21 and decreasing cyclin D1 and E levels. EA also induced caspase-3-mediated apoptosis by increasing the Bax : Bcl-2 ratio and restored anoikis in both cell lines. The enhancement of apoptosis and/or inhibition of autophagy in these cells by EA assisted the chemotherapy efficacy. The results indicated that EA is a potential novel chemoprevention and treatment assistant agent for human ovarian carcinoma.

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Dose-Dependent and Epitope-Specific in Vivo Irradication of the Human Ovarian Carcinoma Cells Expressing the Willms Tumor Protein, WT1, in NOD/SCID Mice, by WT1 Specific T Cells Monitored by Bioluminescent Imaging

Biology of Blood and Marrow Transplantation ◽

10.1016/j.bbmt.2010.12.352 ◽

2011 ◽

Vol 17 (2) ◽

pp. S270

Author(s):

E. Doubrovina ◽

D. Pankov ◽

M. Doubrovin ◽

A. Hasan ◽

R.J. O'Reilly

Keyword(s):

T Cells ◽

Ovarian Carcinoma ◽

Scid Mice ◽

Carcinoma Cells ◽

Bioluminescent Imaging ◽

Ovarian Carcinoma Cells ◽

Human Ovarian Carcinoma ◽

Dose Dependent ◽

Human Ovarian Carcinoma Cells

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Smad4 induces cell death in HO-8910 and SKOV3 ovarian carcinoma cell lines via PI3K-mTOR involvement

Experimental Biology and Medicine ◽

10.1177/1535370220916709 ◽

2020 ◽

Vol 245 (9) ◽

pp. 777-784

Author(s):

Yushuang Yao ◽

Zhe Zhang ◽

Fanmao Kong ◽

Zhuqing Mao ◽

Zhaoyuan Niu ◽

...

Keyword(s):

Cell Viability ◽

Ovarian Carcinoma ◽

Cell Lines ◽

Molecular Mechanisms ◽

Treatment Strategies ◽

Carcinoma Cells ◽

Skov3 Cell ◽

Ovarian Carcinoma Cells ◽

Skov3 Cells ◽

Induced Apoptosis

Ovarian carcinoma is one of the most common malignant cancers in women. Previous research has shown that Smad4 participates in the progression of multiple biological reactions as a crucial regulator. Nevertheless, studies on the role of Smad4 in ovarian carcinoma have been extremely limited. The study aim was to explore the mechanism underlying Smad4 regulation of HO-8910 and SKOV3 cell viability and autophagy. We observed that Smad4 gene expression in ovarian carcinoma tissues and cell lines was downregulated, and Smad4 overexpression resulted in decreased proliferation and increased autophagy in HO-8910 and SKOV3 cells (ovarian carcinoma cells). We also found that Smad4 overexpression induced apoptosis of ovarian carcinoma cells. A co-immunoprecipitation assay also revealed that Smad4 interacted with the P85 subunit of PI3K and caused its degradation and dephosphorylation. Subsequently, expression of mTOR was inhibited. Accordingly, these findings showed that further investigation of the biological mechanisms underlying ovarian carcinoma occurrence and progression is warranted, which may lead to new ovarian carcinoma treatment strategies. Impact statement This study investigated the effect and mechanism of Smad4 in ovarian carcinoma (OC) cell viability and demonstrated that Smad4 acted as a tumor suppressor in OC, which may contribute to the understanding of molecular mechanisms underlying OC occurrence and progression. Smad4 expression was decreased in the OC specimens, but Smad4 recovery in the OC cell lines impaired the survival and viability of OC cells by increasing autophagy and apoptosis. Further investigation showed that Smad4 interacted with the P85 subunit of PI3K and caused deactivation of the PI3K/mTOR pathway. Therefore, Smad4 could be considered as a target in cancer therapy due to its regulatory effect in OC carcinogenesis.

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