Preliminary studies of the effects of gadolinium texaphyrin on the growth and radiosensitivity of EMT6 cells in vitro

Rockwell, Sara; Donnelly, Erling T.; Liu, Yanfeng; Tang, Liang

doi:10.1016/s0360-3016(02)02962-0

Cited by 21 publications

(9 citation statements)

References 13 publications

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“…MGd is a redox active agent that has been shown to redox cycle and form reactive oxygen species in cells (20)(21)(22)(23). Other redox cycling agents have been shown to induce metallothionein expression (36).…”

Section: Discussionmentioning

confidence: 99%

“…For example, motexafin gadolinium (MGd, Xcytrin, Fig. 1A), an expanded porphyrin containing the lanthanide cation gadolinium, is currently in clinical trials for the treatment of several forms of cancer (15)(16)(17)(18)(19)(20)(21)(22)(23). MGd is an electron-affinic compound that mediates electron transfer from a variety of intracellular reducing species, such as ascorbate, NADPH, and thiols, to oxygen to form superoxide and hydrogen peroxide (20)(21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

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Motexafin Gadolinium Disrupts Zinc Metabolism in Human Cancer Cell Lines

et al. 2005

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To gain a better understanding of the mechanism of action of the metal cation-containing chemotherapeutic drug motexafin gadolinium (MGd), gene expression profiling analyses were conducted on plateau phase human lung cancer (A549) cell cultures treated with MGd. Drug treatment elicited a highly specific response that manifested in elevated levels of metallothionein isoform and zinc transporter 1 (ZnT1) transcripts. A549 cultures incubated with MGd in the presence of exogenous zinc acetate displayed synergistic increases in the levels of intracellular free zinc, metallothionein transcripts, inhibition of thioredoxin reductase activity, and cell death. Similar effects were observed in PC3 prostate cancer and Ramos B-cell lymphoma cell lines. Intracellular free zinc levels increased in response to treatment with MGd in the absence of exogenous zinc, indicating that MGd can mobilize bound intracellular zinc. These findings lead us to suggest that an important component of the anticancer activity of MGd is related to its ability to disrupt zinc metabolism and alter cellular availability of zinc. This class of compounds may provide insight into the development of novel cancer drugs targeting control of intracellular free zinc and the roles that zinc and other metal cations play in biochemical pathways relevant to cancer. (Cancer Res 2005; 65(9): 3837-45)

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Motexafin Gadolinium Disrupts Zinc Metabolism in Human Cancer Cell Lines

et al. 2005

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“…In that particular report, the authors found no enhancement in aerated cells either, which conflicts with the original report [11]. However, it was reported that the protocol details, which were not identical, could account for the differences observed between the two reports [32]. It is not known whether CuTCPBr has any selective effect on hypoxic cells and this requires further investigation.…”

Section: Discussionmentioning

confidence: 69%

Enhancement of the radiation response of EMT-6 tumours by a copper octabromotetracarboranylphenylporphyrin

Miura¹,

Morris²,

Hopewell³

et al. 2012

BJR

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Objective: The carborane-containing porphyrin, copper (II) 2,3,7,8,12,13,17,18-octabromo-5,10,15,20-tetrakis(3-[1,2-dicarba-closo-dodecaboranyl]methoxyphenyl)-porphyrin (CuTCPBr), was investigated as a potential radiation enhancing agent for X-ray radiotherapy (XRT) in a subcutaneously implanted EMT-6 murine carcinoma. Method: The biodistribution and toxicological profile of this porphyrin has been shown to be favourable for another bimodal radiotherapy technique, boron neutroncapture therapy. For the XRT studies, CuTCPBr was formulated in either 9% CremophorH (BASF Corporation, Ludwigschafen, Germany) EL and 18% propylene glycol (9% CRM) or a revised formulation comprising 1% Cremophor ELP, 2% Tween 80H (JT Baker, Mansfield, MA), 5% ethanol and 2.2% PEG 400 (CTEP formulation), which would be more clinically acceptable than the original 9% CRM formulation. Using the 9% CRM formulation of CuTCPBr, doses of 100, 210 or 400 mg kg 21 of body weight were used in combination with single doses of 25-35 Gy 100 kVp X-rays. Results: While doses of 100 mg kg 21 and 210 mg kg 21 did not result in any significant enhancement of tumour response, the 400 mg kg 21 dose did. A dose modification factor of 1.20¡0.10 was obtained based on the comparison of doses that produced a 50% local tumour control probability. With the CTEP formulation of CuTCPBr, doses of 83 and 170 mg kg 21 produced significant radiation enhancement, with dose modification factors based on the TCP 50 of 1.29¡0.15 and 1.84¡0.24, respectively. Conclusion: CuTCPBr significantly enhanced the efficacy of XRT in the treatment of EMT-6 carcinomas in mice. The CTEP formulation showed a marked improvement, with over 9% CRM being associated with higher dose modification factors. Moreover, the radiation response in the skin was not enhanced.

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“…In turn, MGd reacts with oxygen to be regenerated by redox cycling, leading to the production of the reactive oxygen species (ROS), superoxide and hydrogen peroxide [17]. Thus MGd is catalyzed as a substrate by mammalian TrxR, generating ROS from NADPH in the presence of oxygen, which kills cancer cells [55,56]. In this particular case, MGd acts as a non-competitive inhibitor for rat TrxR (IC 50 : 6 μM), resulting in the Trx-dependent protein-disulfide reduction of mammalian TrxR is blocked [17].…”

Section: Motexafin Gadolinium (Mgd)mentioning

confidence: 99%

Targeting Thioredoxin Reductase: Anticancer Agents and Chemopreventive Compounds

2010

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Preliminary studies of the effects of gadolinium texaphyrin on the growth and radiosensitivity of EMT6 cells in vitro

Cited by 21 publications

References 13 publications

Motexafin Gadolinium Disrupts Zinc Metabolism in Human Cancer Cell Lines

Motexafin Gadolinium Disrupts Zinc Metabolism in Human Cancer Cell Lines

Enhancement of the radiation response of EMT-6 tumours by a copper octabromotetracarboranylphenylporphyrin

Targeting Thioredoxin Reductase: Anticancer Agents and Chemopreventive Compounds

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