Description of the cytotoxic effect of a novel drug Abietyl-Isothiocyanate on endometrial cancer cell lines

Horan, Timothy C.; Zompa, Michael A.; Seto, Christopher T.; Kim, Kyu Kwang; Moore, Richard G.; Lange, Thilo S.

doi:10.1007/s10637-011-9728-z

Cited by 6 publications

(3 citation statements)

References 46 publications

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“…These changes were still observed after treatment with an antioxidant which, however, could partially block AC‐AM‐induced and ROS‐mediated cell death. This observation is different than the findings by our laboratory to other drugs (e.g., organometallic compound iron(III)‐salophene; ITC derivative ABITC) where ROS generation was the primary mechanism of cytotoxic action in neuroblastoma and endometrial cancer cells and strong activation of p38 and JNK could completely be abolished by cellular co‐treatment with exogenous antioxidants (54,55). Similarly, recent studies suggested that the drug‐induced activation of MAPK including JNK/SAPK and cancer cell apoptosis can be directly ROS dependent (56,57).…”

Section: Discussioncontrasting

confidence: 99%

Cytotoxic Properties of Adamantyl Isothiocyanate and Potential In vivo Metabolite Adamantyl‐N‐Acetylcystein in Gynecological Cancer Cells

et al. 2011

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This study determined the in vitro potential of novel compounds adamantyl-N-acetylcystein and adamantyl isothiocyanate to treat gynecological cancers. Adamantyl-N-acetylcystein is postulated to be an in vivo metabolite of adamantyl isothiocyanate as dietary isothiocyanates are converted to N-acetylcysteine-conjugates. A viability assay suggested that adamantyl isothiocyanate and adamantyl-N-acetylcystein are cytotoxic to cancer cells including gynecological cell lines. A NCI60 cancer cell assay revealed that growth-inhibition and cytotoxicity of adamantyl-N-acetylcystein were cell line, but not tissue type-specific. Cell cycle studies revealed that adamantyl-N-acetylcystein and adamantyl isothiocyanate arrest SKOV-3 ovarian cancer cells in G2 ⁄ M phase. By TUNEL, immunoblotting, and viability studies employing caspase and p38 mitogen-activated protein kinase inhibitors, we proved that reduction in SKOV-3 viability is a consequence of DNA fragmentation and apoptosis. Cytotoxic action of adamantyl-N-acetylcystein in SKOV-3 and endometrial cancer (ECC-1, RL95-2, AN3CA, and KLE) cells required excess generation of reactive oxygen species which could be blocked by antioxidant cotreatment. Adamantyl-N-acetylcystein treatment led to modified expression or activation of apoptotic and oncogenic proteins such as JNK ⁄ SAPK, AKT, XIAP, and EGF-R for SKOV-3 and JNK ⁄ SAPK and ERK1 ⁄ 2 for ECC-1 cells. We suggest the further development of adamantyl-N-acetylcystein by sensitizing cells to the drug using signaling inhibitors or redox-modulating agents and by evaluating the drug efficacy in ovarian and endometrial invivo tumor models.

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Section: Discussioncontrasting

confidence: 99%

Cytotoxic Properties of Adamantyl Isothiocyanate and Potential In vivo Metabolite Adamantyl‐N‐Acetylcystein in Gynecological Cancer Cells

et al. 2011

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“…Chemotherapy, radiation therapy or their combination is chosen for patients with a medium or high recurrence risk. Most endometrial cancer patients were diagnosed in the early stage and treated with surgery alone or with additional radiation therapy ( 3 ). However, a significant proportion of endometrial cancer patients with metastasis or in the advanced stage still require systematic chemotherapy ( 4 , 5 ).…”

Section: Introductionmentioning

confidence: 99%

Paeoniflorin inhibits proliferation of endometrial cancer cells via activating MAPK and NF‑κB signaling pathways

Zhang

Wang

et al. 2017

Exp Ther Med

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Paeoniflorin (PAE), a principal bioactive component of Paeonia lactiflora Pall., appears to have antitumor properties. However, the pharmacological activity of PAE in endometrial cancer and the specific mechanisms have remained largely elusive. The present study aimed to determine the antitumor activity of PAE in the human endometrial cancer cell line RL95-2 and explore the potential mechanisms. Cell proliferation was assessed to evaluate the antitumor effect of PAE towards RL95-2 cells via a Cell Counting Kit-8 assay. Protein expression was examined to investigate changes in the signaling pathways of p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and nuclear factor (NF)-κB in RL95-2 cells during PAE treatment by western blot analysis. The results revealed that PAE significantly and dose- and time-dependently inhibited the proliferation of RL95-2 cells. In addition, PAE activated MAPK signaling pathways (p38, JNK and ERK) and the NF-κB signaling pathway. Furthermore, p38 MAPK and NF-κB inhibitors (SB203580 and MG-132, respectively) prevented PAE-induced proliferative inhibition in RL95-2 cells. However, ERK and JNK inhibitors (PD98059 and BI-78D3, respectively) did not produce such an inhibition. In conclusion, the present study demonstrated that PAE exerts its anti-proliferative activity via activating p38 MAPK and NF-κB signaling pathways in endometrial cancer cells, providing a potential new drug of choice for endometrial cancer therapy.

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“…However, overall survival remains largely unaffected (3). For patients with advanced stage disease or recurrent disease, particularly when it is not amenable to surgical resection, systemic chemotherapy is often required as adjuvant treatment (4). Therefore, it is beneficial to develop a novel therapeutic agent for patients at risk of micrometastatic disease.…”

Section: Introductionmentioning

confidence: 99%

Triptolide induces apoptosis in endometrial cancer via a p53-independent mitochondrial pathway

Wang

Zhao

et al. 2013

Molecular Medicine Reports

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Triptolide (TP), the primary active component purified from the traditional Chinese herbal medicine Tripterygium wilfordii Hook. F (TWHF), has been shown to possess antitumor activity in several types of solid tumors. In the present study, we investigated the antitumor effect of TP in human endometrial cancer cells (HEC-1B) and elucidated its possible underlying mechanisms. HEC-1B cells were treated with various doses of TP (10, 20, 40, 80, 160 and 320 nM), and the cell viability was assessed by Cell Counting Kit-8 (CCK-8) and flow cytometric analysis. Results indicated that TP inhibited the proliferation of HEC-1B cells in a dose- and time‑dependent manner. To further investigate its mechanisms, the levels of apoptosis and the changes in caspase-3/9 expression in HEC-1B cells by pretreatment with z-VAD-fmk, a pan-caspase inhibitor, were detected by CCK-8 and western blotting. The cytotoxic effects of TP were significantly inhibited by z-VAD‑fmk. At the molecular level, TP did not effectively activate the p53 signaling pathway, but upregulated caspase-3/9 and downregulated bcl-2 without changing the bax level. Our studies revealed that TP has an effect on the apoptotic ability of endometrial cancer cells via a p53-independent mitochondrial pathway, presenting a novel strategy to evade drug resistance in tumorigenesis. The ability of TP to be a potential chemotherapeutic agent for endometrial cancer should be considered.

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Description of the cytotoxic effect of a novel drug Abietyl-Isothiocyanate on endometrial cancer cell lines

Cited by 6 publications

References 46 publications

Cytotoxic Properties of Adamantyl Isothiocyanate and Potential In vivo Metabolite Adamantyl‐N‐Acetylcystein in Gynecological Cancer Cells

Cytotoxic Properties of Adamantyl Isothiocyanate and Potential In vivo Metabolite Adamantyl‐N‐Acetylcystein in Gynecological Cancer Cells

Paeoniflorin inhibits proliferation of endometrial cancer cells via activating MAPK and NF‑κB signaling pathways

Triptolide induces apoptosis in endometrial cancer via a p53-independent mitochondrial pathway

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