Experimental investigations on increased resistance to infections with Candida albicans and Staphylococcus aureus Smith by 4-imino-1,4-diazobicyclo-(3.1.0)-hexane-2-on BM 06.002 (Prop. INN Imexon) in mice

Ziegler, AG; Bicker, U.; Hebold, G

doi:10.1016/s0014-4908(77)80051-3

Cited by 3 publications

(1 citation statement)

References 4 publications

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“…On the other hand, two ethylene imine derivatives, azimexon (Bicker, Hebold, Ziegler & Maus, 1978) - Fig. 7 and imexon (Ziegler, Bicker & Hebold, 1977), (Fig. 8) have been reported as immune stimulants.…”

Section: )mentioning

confidence: 99%

Non‐steroidal immunoregulants

1981

Vet Pharm & Therapeutics

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Section: )mentioning

confidence: 99%

Non‐steroidal immunoregulants

1981

Vet Pharm & Therapeutics

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5 Amidines and Guanidines in Medicinal Chemistry

Greenhill

Lue

1993

Progress in Medicinal Chemistry

250

145

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Imexon-Induced Apoptosis in Multiple Myeloma Tumor Cells Is Caspase-8 Dependent

Evens

Prachand

Shi

et al. 2004

Clinical Cancer Research

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Purpose: Imexon is a 2-cyanoaziridine agent that has been shown to inhibit growth of chemotherapy-sensitive myeloma cells through apoptosis with decreased cellular stores of glutathione and increased reactive oxygen species (ROS). We examined the mechanism of imexon cytotoxicity in a diverse panel of dexamethasone and chemotherapysensitive and -resistant myeloma cell lines.Experimental Design: We examined cellular cytotoxicity, apoptosis, and changes in redox state in dexamethasonesensitive (C2E3), dexamethasone-resistant (1-310 and 1-414), chemotherapy-sensitive (RPMI-8226), and chemotherapy-resistant (DOX-1V and DOX-10V) myeloma cell lines.Results: We found significant cytotoxicity after 48-h incubation with imexon (80 -160 M) in dexamethasone and chemotherapy-sensitive and -resistant myeloma cell lines in a time-and dose-dependent manner. The mechanism of imexon cytotoxicity in all cell lines was related to induction of apoptosis with the presence of cleaved caspase-3. Moreover, after imexon exposure in C2E3 and 1-414 cell lines, we demonstrated caspase-8-dependent apoptosis. Bcl-2:bax was proapoptotic with imexon in C2E3, whereas bcl-2:bax was independent of steroid resistance, chemotherapy sensitivity, and chemotherapy resistance. Depletion of intracellular glutathione was documented in RPMI-8226 at high imexon concentrations (>225 M) but not in other cell lines. Furthermore, ROS were found in C2E3, RPMI-8226, and 1-310 only at high imexon concentrations, whereas a sensitive marker of oxidative DNA damage, 8-hydroxydeoxyguanosine, was not increased in any cell line.Conclusions: Our results demonstrate that imexon has significant broad antimyeloma activity that is mediated through apoptotic mechanisms that is not dependent on production of ROS. Moreover, we have identified a mechanism of cytotoxicity in dexamethasone-sensitive and -resistant myeloma cells induced by imexon that is caspase-8 dependent.

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Experimental investigations on increased resistance to infections with Candida albicans and Staphylococcus aureus Smith by 4-imino-1,4-diazobicyclo-(3.1.0)-hexane-2-on BM 06.002 (Prop. INN Imexon) in mice

Cited by 3 publications

References 4 publications

Non‐steroidal immunoregulants

Non‐steroidal immunoregulants

5 Amidines and Guanidines in Medicinal Chemistry

Imexon-Induced Apoptosis in Multiple Myeloma Tumor Cells Is Caspase-8 Dependent

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