Mechanism of differential sensitivity of human bladder cancer cells to mitomycin C and its analogue

Xu, Baocheng; Gupta, V. D.; Singh, Shivendra V.

doi:10.1038/bjc.1994.46

Cited by 18 publications

(7 citation statements)

References 21 publications

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“…Moreover, a direct correlation between the levels of FpT activity and the toxicity of MC has been shown for cell lines selected for resistance to this drug (27,28) and for other cell lines having different intrinsic sensitivities to MC (29). However, in each of these investigations, the activities of only one or two enzymes involved in activating the mitomycins were measured (27)(28)(29), and cell lines of different origins were compared without regard to their genetic heterogeneity (27)(28)(29). This leaves open the question as to whether other genetic changes or enzyme systems also contributed to the resistant phenotype.…”

Section: Discussionmentioning

confidence: 99%

Differential toxicity of mitomycin C and porfiromycin to aerobic and hypoxic Chinese hamster ovary cells overexpressing human NADPH:cytochrome c (P-450) reductase.

Belcourt

Hodnick

Rockwell

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

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Purified NADPH:cytochrome c (P-450) reductase (FPT; NADPH-ferrihemoprotein oxidoreductase, EC (for appropriate references, see refs. 9-11). Evidence exists to suggest that alkylation of DNA is the critical lesion in the cytotoxicity of the mitomycins to both hypoxic and oxygenated cells (12, 13).Studies in mice bearing transplanted solid tumors demonstrated the ability of these antibiotics to reach and kill hypoxic cells and, in combination with x-irradiation, to produce additive or greater than additive cytotoxicity to tumor cells without a corresponding increase in toxicity to normal tissues (10,11

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Section: Discussionmentioning

confidence: 99%

Differential toxicity of mitomycin C and porfiromycin to aerobic and hypoxic Chinese hamster ovary cells overexpressing human NADPH:cytochrome c (P-450) reductase.

Belcourt

Hodnick

Rockwell

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

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“…Both compounds retained the core mitomycin ring system but replaced the C(7) amine unit in 8 with a C(7) aminoethylene disulfide group. The compounds, 1a and 1b, exhibited improved biological profiles compared with 8, which represented 10~100-fold higher cytotoxicities in tumor cell lines (Ohe et al, 1989;Bradner et al, 1990;Ashizawa et al, 1993;Dirix et al, 1994;Xu et al, 1994;Rockwell et al, 1995), more efficient cellular uptake, and increased rates of drug accumulation in nuclei (Kono et al, 1989;Kobayashi et al, 1993b). Significantly, these compounds exhibited pharmacological activity both in 8-resistant tumor cell lines and in non-hypoxic cells (Tsuruo et al, 1990;Morimoto et al, 1991;Kobayashi et al, 1993a).…”

Section: Mitomycin Disulfidesmentioning

confidence: 98%

Disulfide and multisulfide antitumor agents and their modes of action

Lee

2009

Arch. Pharm. Res.

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A variety of natural products that contain disulfide or multisulfide bonds were found to display potent biological activities, including antitumor activities. At the center of these biological activities are disulfide or multisulfide moieties. The importance of disulfide or multisulfide groups in the areas of chemistry, biology, and pharmacology has been well recognized. Among these agents, especially noteworthy are mitomycin disulfides, leinamycin, thiarubrines, varacins, calicheamicins, and esperamicins. Their general features, including their biological profiles, peculiar structures, and related chemistries, were summarized and more importantly, their working mechanisms were elucidated in detail in this review. Mechanistic studies of these compounds have provided evidence of the key role of disulfide or multisulfide groups. In general, the cleavage of disulfide or multisulfide bonds produces thiol (or thiolate), which triggers an activation cascade leading to the generation of highly reactive electrophile(s) or cytotoxic species that may cause DNA strand scission. The main concerns with the mode of action are the reactivity and stability of disulfide and multisulfide bonds, their cleavage conditions, and the generation of toxic species. A range of studies for each agent was executed to gather important information on their activation, and the obtained information was gradually integrated to give some clues to the agents' working mechanisms. Such information may be further used to generate biomechanistically designed and more potent derivatives.

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“…Numerous individuals with heart disease in China also take MMC (27,28). However, occurrence of resistance to MMC often limits its clinical effectiveness (12)(13)(14). To increase MMC chemotherapy sensitivity, MMC is often combined with other agents (17).…”

Section: Discussionmentioning

confidence: 99%

“…It functions by binding to the DNA of cancer cells to prevent cell division and thereby inhibit the growth of the cancer. However, its clinical effectiveness is limited bythe occurrence of resistance to MMC (12)(13)(14). To overcome this treatment resistance, MMC is often combined with other agents to increase MMC chemotherapy sensitivity (15).…”

Section: Introductionmentioning

confidence: 99%

Effect of selective inhibition of aquaporin 1 on chemotherapy sensitivity of J82 human bladder cancer cells

Zhang

Chen²,

Dong³

et al. 2018

Oncol Lett

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Abstract. The occurrence of resistance to mitomycin C (MMC) often limits its clinical effectiveness. Combination therapy thus is employed to overcome this treatment resistance. The present study aimed to establish a novel J82 bladder cancer cell line so as to study the effect of inhibition of aquaporin 1 (AQP-1) on chemotherapy sensitivity of J82 bladder cancer cells. A novel J82 bladder cancer cell line whose expression of AQP-1 is inhibited was established through transfection of J82 cells with newly constructed recombinant plasmid. The resulting cell line was designated J82-short hairpin (sh)AQP1 and was subjected to further analyses together with J82 cell line. Reverse transcription-polymerase chain reaction was used to quantify the expression of AQP-1mRNA in the cells; cell viability was analyzed with MTT assay and apoptosis was measured by flow cytometry. The expression of cell proliferation and cell apoptosis-associated proteins, proliferating cell nuclear antigen (PCNA), B cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax) and caspase-3, were detected by Western blot. A statistically significant decrease in the transcription and expression of AQP1 was observed in the J82-shAQP1 cells as compared with J82 cells. J82-shAQP1 cells treated by MMC, also had a lower cell viability than J82 cells treated by MMC and showed enhanced apoptosis. Western blot analysis revealed J82-shAQP1 cells treated by MMC had less expression of PCNA, lower bcl-2/Bax ratio and more expression of caspase-3 as compared with the J82 cells treated by MMC. Selective inhibition of AQP-1 enhanced MMC chemotherapy sensitivity of J82 bladder cancer cells, suggesting combination of AQP-1 inhibition with MMC treatment as a promising treatment strategy to overcome bladder cancer treatment resistance.

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Mechanism of differential sensitivity of human bladder cancer cells to mitomycin C and its analogue

Cited by 18 publications

References 21 publications

Differential toxicity of mitomycin C and porfiromycin to aerobic and hypoxic Chinese hamster ovary cells overexpressing human NADPH:cytochrome c (P-450) reductase.

Differential toxicity of mitomycin C and porfiromycin to aerobic and hypoxic Chinese hamster ovary cells overexpressing human NADPH:cytochrome c (P-450) reductase.

Disulfide and multisulfide antitumor agents and their modes of action

Effect of selective inhibition of aquaporin 1 on chemotherapy sensitivity of J82 human bladder cancer cells

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