Enhancement of thermal killing by polyamines. I. Survival of chinese hamster cells

Ben‐Hur, E.; Prager, A.; Riklis, E.

doi:10.1002/ijc.2910220515

Cited by 34 publications

(11 citation statements)

References 15 publications

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“…25 Moreover, in these experimental conditions, the data clearly showed the essential role of enzymatic oxidation products of polyamines, rather than polyamines themselves, in inducing the cytotoxic effect. 37 The results indicated that at low spermine concentrations H 2 O 2 was the enzymatic product responsible for most of the cytotoxic effect observed in both cell lines. The involvement of H 2 O 2 , formed in the incubation mixture, was demonstrated by the marked protection afforded by exogenous catalase and by the fact that most of the H 2 O 2 molecules were removed from the incubation mixture and taken up by the cells, as determined by fluorometric methods.…”

Section: Discussionmentioning

confidence: 92%

Enzymatic oxidation products of spermine induce greater cytotoxic effects on human multidrug‐resistant colon carcinoma cells (LoVo) than on their wild‐type counterparts

Calcabrini¹,

Arancia²,

Marra³

et al. 2002

Intl Journal of Cancer

122

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The occurrence of resistance to cytotoxic agents in tumor cells, associated with several phenotypic alterations, is one of the major obstacles to successful anticancer chemotherapy. A new strategy to overcome MDR of human cancer cells was studied, using BSAO, which generates cytotoxic products from spermine, H 2 O 2 and aldehyde(s). The involvement of these products in causing cytotoxicity was investigated in both drug-sensitive (LoVo WT) and drug-resistant (LoVo DX) colon adenocarcinoma cells. Evaluation of clonogenic cell survival showed that LoVo DX cells are more sensitive than LoVo WT cells. Fluorometric assay and treatments performed in the presence of catalase demonstrated that the cytotoxicity was due mainly to the presence of H 2 O 2 . Cytotoxicity was eliminated in the presence of both catalase and ALDH. Transmission electron microscopic observations showed more pronounced mitochondrial modifications in drug-resistant than in drug-sensitive cells. Mitochondrial functionality studies performed by flow cytometry after JC-1 labeling revealed basal hyperpolarization of the mitochondrial membrane in LoVo DX cells. After treatment with BSAO and spermine, earlier and higher mitochondrial membrane depolarization was found in LoVo DX cells than in drug-sensitive cells. In addition, higher basal ROS production in LoVo DX cells than in drug-sensitive cells was detected by flow-cytometric analysis, suggesting increased mitochondrial activity in drug-resistant cells. Our results support the hypothesis that mitochondrial functionality affects the sensitivity of cells to the cytotoxic enzymatic oxidation products of spermine, which might be promising anticancer agents, mainly against drug-resistant tumor cells.

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Section: Discussionmentioning

confidence: 92%

Enzymatic oxidation products of spermine induce greater cytotoxic effects on human multidrug‐resistant colon carcinoma cells (LoVo) than on their wild‐type counterparts

Calcabrini¹,

Arancia²,

Marra³

et al. 2002

Intl Journal of Cancer

122

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“…However, very low spermine concentrations alone, as used in our experimental conditions, did not induce any cytotoxic effect in either cell line. In fact, the findings clearly showed the essential role of enzymatic oxidation products of polyamines (24,25,27,33,56), rather than polyamines themselves, in causing cytotoxicity (57).…”

Section: Discussionmentioning

confidence: 94%

Hyperthermia enhances cytotoxicity of amine oxidase and spermine on drug-resistant LoVo colon adenocarcinoma cells

Agostinelli¹,

Belli²,

Vedova³

et al. 2006

Int J Oncol

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Abstract. Hyperthermia is currently receiving widespread attention when associated with other therapeutic modalities, such as irradiation or chemotherapy, in the treatment of cancer. The occurrence of resistance to cytotoxic pharmacological agents in tumor cells, associated with several phenotypic alterations, is one of the major obstacles to successful anticancer chemotherapy. We investigated a new strategy to overcome multidrug resistance (MDR) cancer cells, using bovine serum amine oxidase (BSAO), which forms toxic products from spermine (H 2 O 2 and aldehydes). The cytotoxicity of the products was evaluated in drug-sensitive (LoVo WT) and multidrug-resistant (LoVo DX) colon adenocarcinoma cells at 37 and 42˚C, using a clonogenic cell survival assay. Cytotoxicity was considerably enhanced at 42˚C. Both toxic species contributed to the thermal enhancement of cytotoxicity induced by BSAO and spermine. Cytotoxicity was eliminated in the presence of catalase and aldehyde dehydrogenase (ALDH). An interesting finding was that BSAO and spermine at <1 μM, which were non toxic at 37˚C, became cytotoxic at 42˚C and resemble thermosensitizers. Cell survival results and electron microscopy investigations suggest that, at 42˚C, LoVo DX cells are not resistant to the cytotoxic enzymatic oxidation products of spermine, as was already demonstrated in these cells at 37˚C. Moreover, microscopy modifications caused by both toxic products were more pronounced in LoVo DX than in LoVo WT cells, where morphological cytoplasmatic alterations were shown. Our findings suggest that hyperthermia combined with the enzymatic toxic oxidation products of spermine might be a promising anticancer strategy, mainly against MDR tumor cells.

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“…The mechanistic photochemistry of several phthalocyanines has been investigated in recent years (Day et al, 1968;McVie et al, 1978;Dolphin et al, 1980;Harriman and Richoux, 1980;Lever et al, 1981;Muralidharan and Ferrandi, 1983). Following our initial observation that CAPC is a potent photosensitizer in mammalian cells (Ben-Hur and Rosenthal, 1985), we now report the characteristics of the response of Chinese hamster cells exposed to CAPC and visible light. It is noteworthy that CAPC photosensitization, although requiring 0 2 , probably does not involve lo2 suggesting a Type I photodynamic reaction.…”

Section: Introductionmentioning

confidence: 94%

“…In search for alternative sensitizers for PDT, we reported the photobiological activity of CAPC (Ben-Hur and Rosenthal, 1985). Metallophthalocyanines are porphyrin-like compounds ( Fig.…”

Section: Introductionmentioning

confidence: 99%

Photosensitized Inactivation of Chinese Hamster Cells by Phthalocyanines

Ben‐Hur¹,

Rosenthal

1985

Photochem & Photobiology

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Chloroaluminum phthalocyanine was found to sensitize cultured Chinese hamster cells upon exposure to white fluorescent light. Elimination of wavelengths below 370 nm did not reduce the effect significantly, indicating that the effective wavelengths were those absorbed by the Q band (600–700 nm) of phthalocyanine. The magnitude of the photosensitizing effect increased with the dye concentration and the time of its contact with the cells prior to light exposure. Although photosensitization was drastically reduced in the absence of oxygen, the lack of effect of glycerol and D20 during exposure suggests that neither hydroxyl radicals nor 1O2 are responsible for the cytotoxic response. The efficiency of the photosensitized induced cell killing did not vary with the position of the cells in the cell cycle, in contrast to exposure to X‐rays. The improved spectral properties, the reported low toxicity and the selective retention by neoplasms, make phthalocyanines promising candidates for use in photodynamic therapy of cancer.

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Enhancement of thermal killing by polyamines. I. Survival of chinese hamster cells

Cited by 34 publications

References 15 publications

Enzymatic oxidation products of spermine induce greater cytotoxic effects on human multidrug‐resistant colon carcinoma cells (LoVo) than on their wild‐type counterparts

Enzymatic oxidation products of spermine induce greater cytotoxic effects on human multidrug‐resistant colon carcinoma cells (LoVo) than on their wild‐type counterparts

Hyperthermia enhances cytotoxicity of amine oxidase and spermine on drug-resistant LoVo colon adenocarcinoma cells

Photosensitized Inactivation of Chinese Hamster Cells by Phthalocyanines

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