Effects of calmodulin antagonists on human ovarian cancer cell proliferation in vitro

Kikuchi, Yoshihiro; Iwano, Ichiro; Kato, Koichi

doi:10.1016/0006-291x(84)90425-x

Cited by 40 publications

(10 citation statements)

References 8 publications

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“…Two cell lines, KF and KFr, did not express DAPK as a result of DNA methylation. These cells were originally established from serous cystadenocarcinoma cell lines and are relatively resistant to chemotherapeutic drugs (24,36). It is thus plausible that epigenetic inactivation of DAPK provides cancer cells with the ability to escape apoptosis triggered by the DAPK signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Inactivation of TMS1/ASC in Ovarian Cancer

Terasawa

Sagae

Toyota

et al. 2004

Clinical Cancer Research

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Purpose: The purpose of this work was to explore the role of epigenetic inactivation of apoptotic pathways in ovarian cancer by examining the DNA methylation and expression status of four proapoptotic genes in primary ovarian cancers and cancer cell lines and to correlate those findings with the clinicopathological features of ovarian cancer patients.Experimental Design: Genomic DNA was isolated from 15 ovarian cancer cell lines, 80 primary ovarian cancer specimens, and 4 normal ovary specimens using phenolchloroform extraction. The methylation status of the DNA was evaluated using combined bisulfite restriction analysis, gene expression was evaluated using reverse transcription-PCR, and histone acetylation was evaluated using chromatin immunoprecipitation.Results

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Section: Discussionmentioning

confidence: 99%

Epigenetic Inactivation of TMS1/ASC in Ovarian Cancer

Terasawa

Sagae

Toyota

et al. 2004

Clinical Cancer Research

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“…In practice, earlier human clinical trials with such combination therapy [e.g., trifluoperazine and bleomycin for patients with glioblastoma] were carried out in 1980s (8); however, there have been no drugs that have been approved or progressed beyond phase II clinical evaluation with CaM inhibition as a mechanism of action. Cisplatin is one such widely used anticancer agent that had been reported to have its cytotoxicity enhanced by the napthanesulfonamide class of CaM inhibitors (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

CBP501-Calmodulin Binding Contributes to Sensitizing Tumor Cells to Cisplatin and Bleomycin

Mine

Yamamoto

Saito

et al. 2011

Molecular Cancer Therapeutics

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CBP501 is an anticancer drug currently in randomized phase II clinical trials for patients with non-small cell lung cancer and malignant pleural mesothelioma. CBP501 was originally described as a unique G 2 checkpoint-directed agent that binds to 14-3-3, inhibiting the actions of Chk1, Chk2, mitogen-activated protein kinase-activated protein kinase 2, and C-Tak1. However, unlike a G 2 checkpoint inhibitor, CBP501 clearly enhances the accumulation of tumor cells at G 2 -M phase that is induced by cisplatin or bleomycin at low doses and short exposure. By contrast, CBP501 does not similarly affect the accumulation of tumor cells at G 2 -M that is induced by radiation, doxorubicin, or 5-fluorouracil treatment. Our recent findings point to an additional mechanism of action for CBP501. The enhanced accumulation of tumor cells at G 2 -M upon combined treatment with cisplatin and CBP501 results from an increase in intracellular platinum concentrations, which leads to increased binding of platinum to DNA. The observed CBP501-enhanced platinum accumulation is negated in the presence of excess Ca 2þ . Some calmodulin inhibitors behave similarly to, although less potently than, CBP501. Furthermore, analysis by surface plasmon resonance reveals a direct, high-affinity molecular interaction between CBP501 and CaM (K d ¼ 4.62 Â 10 À8 mol/L) that is reversed by Ca 2þ , whereas the K d for the complex between CBP501 and 14-3-3 is approximately 10-fold weaker and is Ca 2þ independent. We conclude that CaM inhibition contributes to CBP501 0 s activity in sensitizing cancer cells to cisplatin or bleomycin. This article presents an additional mechanism of action which might explain the clinical activity of the CBP501-cisplatin combination.

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“…The human ovarian cancer cell line [6], designated KF, established from serous eystadenocarcinoma of the ovary, was exclusively used. The cells were cultured in RPMI-1640 medium supplemented with 10% fetal calf serum, 2 mM glutamine, penicillin (100 units/ml), and streptomycin (100 txg/ml) (Grand Island Biological Co.) in a 5% CO2 atmosphere at 37 ° C. The medium was changed every 3 days, and the cells were passed when confluency was achieved.…”

Section: Methodsmentioning

confidence: 99%

“…We have established a human ovarian cancer cell line transplantable to nude mice and designated it "KF" [6]. We have also demonstrated that the KF cell proliferation was dose-dependently inhibited by endorphins and to less extent [Met]enkephalin [7].…”

Section: Offprint Requests To: Y Kikuchimentioning

confidence: 98%

Effects of opioid peptides on the cellular immunity in spleen cells from intact nude mice or nude mice bearing human ovarian carcinoma

Kikuchi

Kita

Nagata

1990

Cancer Immunol Immunother

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The present study was designed to explore the effects of opioid peptides on the lytic activity of spleen cells from intact nude mice or nude mice bearing human ovarian cancer cells (KF). When the spleen cells from intact nude mice were incubated with various concentrations of opioid peptides, the ability of the spleen cells to lyse the KF cells was significantly stimulated between 0.05 nM and 50 nM concentrations of all opioid peptides used in this study. The degree of stimulation was most marked at 5 nM opioid peptides and the most marked stimulatory effect was obtained by alpha-endorphin. On the other hand, the lytic activity of spleen cells from nude mice challenged with the KF cells was about two-fold higher than that of intact nude mice, suggesting that spleen cells from nude mice challenged with KF cells have KF-cell-specific cytotoxicity. Even if the spleen cells were incubated with any concentration of alpha-endorphin or [Met]enkephalin indicated, the lytic activity remained unchanged. In contrast, only beta-endorphin resulted in a significant increase of the lytic activity between 0.5 nM and 50 nM. These results suggest that opioid peptides play a crucial role in immune surveillance mechanisms.

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Effects of calmodulin antagonists on human ovarian cancer cell proliferation in vitro

Cited by 40 publications

References 8 publications

Epigenetic Inactivation of TMS1/ASC in Ovarian Cancer

Epigenetic Inactivation of TMS1/ASC in Ovarian Cancer

CBP501-Calmodulin Binding Contributes to Sensitizing Tumor Cells to Cisplatin and Bleomycin

Effects of opioid peptides on the cellular immunity in spleen cells from intact nude mice or nude mice bearing human ovarian carcinoma

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