Accumulation of Chlorpromazine and Thiouracil by Human Melanoma Cells in Culture

Parsons, Peter G.; Allen, B.J.

doi:10.1038/icb.1986.56

Cited by 11 publications

(3 citation statements)

References 14 publications

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“…In addition, we observed significantly increased level of MITF protein, reduced cytotoxicity, and motility in human melanotic melanoma after perphenazine and prochlorperazine treatment. (Kuzu et al 2017)) is frequently observed as well as higher sensitivity of amelanotic melanoma (MM96L) in comparison to melanotic (MM96E) after chlorpromazine treatment was also observed (Parsons and Allen 1986). In accordance with these reports, we find concentration-dependent loss in both human melanoma cells viability treated with perphenazine and prochlorperazine.…”

Section: Discussionsupporting

confidence: 90%

Antimelanoma activity of perphenazine and prochlorperazine in human COLO829 and C32 cell lines

Otręba

Pajor

Warncke

2019

Naunyn-Schmiedeberg's Arch Pharmacol

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Cutaneous melanoma is least common (only about 1% of skin cancers) but is the deadliest malignant tumor. Moreover, amelanotic types of melanoma are very difficult for clinical diagnosis. The standard therapy can cause a lot of side effects, e.g., nausea, vomiting, and headaches, which means that novel and effective strategies are required. Interestingly, phenothiazine derivatives possess sedative, antiemetic, and anticancer activity. Our goal was to determine the effect of perphenazine and prochlorperazine on cell viability, motility, microphthalmia-associated transcription factor (MITF) and tyrosinase content in melanotic and amelanotic melanoma cells. The viability of C32 and COLO829 melanoma cells was evaluated by the WST-1 colorimetric assay; impact on motility of human melanoma was performed by wound-healing assay, while tyrosinase and MITF content were determined by Western blot. In the present study, we explore the anticancer effect of perphenazine and prochlorperazine in human melanotic (COLO829) and amelanotic (C32) melanoma cells concluding that prochlorperazine inhibits cell viability in a concentration-dependent manner, impairs motility, and decreases tyrosinase and MITF amounts. Moreover, the analyzed drugs decrease/increase MITF amount depending on the type of melanoma. We demonstrated that the decrease of MITF and tyrosinase protein induces motility inhibition of C32 cells, which suggests the ability of those drugs to restore cancer cell sensitivity to treatment. The ability of prochlorperazine to contain the spread of the amelanotic melanoma in vivo may be helpful in the development of a new and effective antimelanoma therapies.

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Section: Discussionsupporting

confidence: 90%

Antimelanoma activity of perphenazine and prochlorperazine in human COLO829 and C32 cell lines

Otręba

Pajor

Warncke

2019

Naunyn-Schmiedeberg's Arch Pharmacol

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“…For more details about these studies, please refer to them directly. [94][95][96][97] BNCT clinical trials have been carried out in the United States, 98 Finland, 99 Japan, 100 Taiwan, 101 Argentina, 102 Netherland, 103 Italy, 104 Germany, 105 Sweden 106 and the Czech Republic. 107 This treatment modality has been applied for the treatment of brain (glioblastoma multiforme, malignant glioma, and malignant meningioma), liver, head and neck, lung, colon, melanoma, thyroid, hepatic, gastrointestinal cancer, and extra-mammary Paget's disease.…”

Section: Clinical Studies Of Nct For Various Cancersmentioning

confidence: 99%

Physical, dosimetric and clinical aspects and delivery systems in neutron capture therapy

Farhood

Samadian

Ghorbani

et al. 2018

Reports of Practical Oncology & Radiotherapy

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Neutron capture therapy (NCT) is a targeted radiotherapy for cancer treatment. In this method, neutrons with a spectra/specific energy (depending on the type of agent used for NCT) are captured with an agent that has a high cross-section with these neutrons. There are some agents that have been proposed in NCT including B,Gd and S. Among these agents, onlyB is used in clinical trials. Application of Gd is limited to in-vivo and in-vitro research. In addition,S has been applied in the field of Monte Carlo simulation. In BNCT, the only two delivery agents which are presently applied in clinical trials are BPA and BSH, but other delivery systems are being developed for more effective treatment in NCT. Neutron sources used in NCT are fission reactors, accelerators, and Cf. Among these, fission reactors have the most application in NCT. So far, BNCT has been applied to treat various cancers including glioblastoma multiforme, malignant glioma, malignant meningioma, liver, head and neck, lung, colon, melanoma, thyroid, hepatic, gastrointestinal cancer, and extra-mammary Paget's disease. This paper aims to review physical, dosimetric and clinical aspects as well as delivery systems in NCT for various agents.

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“…Three human cell lines, MM418, MM96E, and MM96L, from the Queensland Institute of Medical Research were tested for uptake and incorporation of chlorpromazine (CPZ) and thiouracil (TU) (Parsons and Allen, 1986). After cloning hundreds of millions of cells at Lucas Heights, the cells were characterised and tested in vitro, and in vivo xenografts were grown in the nude mouse model.…”

Section: Melanoma Cell Linesmentioning

confidence: 99%

Neutron Capture Therapy Research in Australia

Allen

1989

Pigment Cell Research

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Neutron capture therapy research in Australia has continued to grow since the first Australia-Japan workshop in April, 1986. The support base has broadened and the wide range of contributing laboratories includes universities, research institutes, and hospitals. Considerable progress has been made in boron chemistry--an accurate boron assay technique has been developed, boron analogues of chlorpromazine and thiouracil have been synthesised or nearly so, and decaborane conjugation with monoclonal antibodies has been achieved to the required loadings. In vitro cell survival experiments are proceeding in the Moata reactor using human melanoma and mouse cell lines incubated with enriched boronophenylalanine and boron tetraphenyl porphyrins. Electron microscopy examination of radiation damaged morphology shows considerable differences between cell lines. Progress with the nude mouse human melanoma model has been slow because of the lack of a reliable in vivo melanotic melanoma line, and the B16 mouse line is found to be more efficacious. Tailored beam calculations for the 10 MW HIFAR reactor indicate the difficulty of obtaining a suitable therapeutic beam because of the generated gamma dose in the beam filters. A new approach to NCT utilises the enormous cross section of 157Gd and the induced-Auger effect which has been shown to cause double strand breaks in circular DNA.

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Accumulation of Chlorpromazine and Thiouracil by Human Melanoma Cells in Culture

Cited by 11 publications

References 14 publications

Antimelanoma activity of perphenazine and prochlorperazine in human COLO829 and C32 cell lines

Antimelanoma activity of perphenazine and prochlorperazine in human COLO829 and C32 cell lines

Physical, dosimetric and clinical aspects and delivery systems in neutron capture therapy

Neutron Capture Therapy Research in Australia

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