Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.3.5.1 (succinate dehydrogenase)
 8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

When the plasma membrane capacity to maintain an ionic gradient is correlated with the cell viability, the anticancer drug-induced-cation (K+, Ca2+) mobilization, an early event associated with cell death, might be used as a rapid in vitro drug sensitivity test. A cyanine dye, dis-C3-5, was used to determine the membrane potential (Em), which was calculated as the following formula; Em = -RT/F In ([K+] in/[K+] out) in cancer cell lines. The change in cytoplasmic free calcium ion ([Ca2+]i) mobilization induced by the drugs was measured by fluorescent dye Fura2-AM. The results suggest that the sensitive drug, which showed greater than or equal to 50% inhibition of succinate dehydrogenase activity in SDI test, induced greater than or equal to 30% fall of membrane potential after 2 hour exposure to the drugs and also induced [Ca2+]i mobilization. On the other hand, the resistant drug showed no change of Em and [Ca2+]i.
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PMID:[Monitoring of the effect of anticancer drugs on the membrane potential and cytoplasmic free calcium ion mobilization in cancer cells as a drug sensitivity test]. 245 72

The ability of injected Photofrin II, a preparation enriched in hydrophobic dihaematoporphyrin ethers and esters, to photosensitize selected mitochondrial and cytosolic enzymes during illumination in vitro was examined. Preparations of R3230AC mammary tumours, obtained at designated times after a single dose of Photofrin II, displayed a time-dependent photosensitivity. Maximum inhibition of mitochondrial enzymes occurred at 24 hours post-treatment, whereas no inhibition of the cytosolic enzyme, pyruvate kinase, was observed over the 168 hour time course. At the selected 24 hour time point, mitochondrial enzyme photosensitisation was found to be drug dose (5.25 mg kg-1 Photofrin II) and light dose dependent, the rank order of inhibition being cytochrome c oxidase greater than F0F1 ATPase greater than succinate dehydrogenase greater than NADH dehydrogenase. We conclude that porphyrin species contained in Photofrin II accumulate in mitochondria of tumour cells in vivo and produce maximum photosensitisation at 24-72 hours after administration to tumour-bearing animals. The time course observed here with Photofrin II is similar to that seen previously with the more heterogenous haematoporphyrin derivative preparation in this in vivo-in vitro model.
Br J Cancer 1989 Jan
PMID:In vitro photosensitization of tumour cell enzymes by photofrin II administered in vivo. 254 13

In order to determine the most effective anticancer agents for individual human tumor, succinic dehydrogenase inhibition test (SDI-T) and adenosine triphosphate inhibition assay (ATP-A) as in vitro chemosensitivity tests were performed. Fifty tumors and 57 tumors derived from cancer patients surgically methods were examined by SDI-T and ATP-A respectively. As the results, the evaluable rate was 70% by SDI-T and 94.7% by ATP-A, respectively. With SDI-T, the positive rate against all tumors was 51.4% in mitomycin-C (MMC), 42.9% in adriamycin (ADM), 20.0% in 5-fluorouracil (5-FU), 54.3% in cis-diamminedichloroplatinum (CDDP). On the other hand, with ATP-A, that was 20.4% in MMC, 29.5% in ADM, 20.6% in 5-FU, 20.4% in CDDP, respectively. Retrospective and prospective clinical trials were also carried out to determine the usefulness of both assays. With SDI-T, overall predictive accuracy rate was 57.1% while with ATP-A that was 88.9%. Furthermore, the rates of sensitivity for the same tumors using SDI-T and ATP-A were compared. The rate of the same sensitive cases in both assays were 30% with MMC, 70% with 5-FU, 42.1% with ADM, 36.8% with CDDP, respectively. In conclusion, it is suggested that ATP-A was more useful than SDI-T as in vitro chemosensitivity test to determine the most adequate drug for cancer patients.
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PMID:[Comparison of succinic dehydrogenase inhibition test with adenosine triphosphate inhibition assay for human solid tumors as in vitro chemosensitivity tests]. 273 92

The sensitivities of 84 human tumor tissues (23 gastric, 8 colorectal cancers, 34 hepatomas, 6 breast, 6 lung cancers and 7 malignant lymphomas) to adriamycin (ADM) and 4'-0-tetrahydropyranyladriamycin (THP-ADM), a semisynthetic anthracycline glycoside, were determined using the in vitro succinate dehydrogenase inhibition (SDI) test. The succinate dehydrogenase (SD) activity of the tumor tissues was assayed following exposure to 6.9 microM of the drug for 3 days; sensitivity was considered positive when the SD activity decreased to below 50% of that of the control cells. In the case of exposure to THP-ADM, the SD activity in the tissue decreased and the decrease was more extensive in the gastric, colorectal cancers, hepatomas, lung cancers, with a statistically significant difference (P less than 0.001-P less than 0.05), but not in the breast cancers and malignant lymphomas. The rate of sensitivity was 70.2% for THP-ADM and 51.2% for ADM in the 84 tumor tissues. The percentage of tissues with a higher sensitivity to THP-ADM, compared to ADM, was 79.8%. As THP-ADM proved to be more cytotoxic than ADM to human tumors in vitro, this drug should be kept in mind when anti-cancer chemotherapy is designed.
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PMID:4'-O-tetrahydropyranyladriamycin has greater antineoplastic activity than adriamycin in various human tumours in vitro. 275 Dec 63

Histochemical distribution of lactate, isocitrate and succinate dehydrogenases in normal oral epithelium and in well differentiated squamous cell carcinoma of cheek region was studied. Lactate dehydrogenase, isocitrate dehydrogenase, and succinate dehydrogenase activity was found to be more in the malignant cells. Succinate and lactate dehydrogenase presented a conspicuous pattern in which the cells located at the periphery of the malignant sheets in well differentiated squamous cell carcinoma showed moderate to intense activity as compared to cells in the central portion. The results are discussed and it is suggested that the enhanced glycolysis and subdued function of the tricarboxylic acid cycle is not a universal criterion during malignancy as reported in the previous investigations.
Indian J Cancer 1989 Mar
PMID:Histochemical studies on the distribution of certain dehydrogenases in squamous cell carcinoma of cheek. 277 29

The synthetic "picket fence" porphyrin, tetra(o-acetamidophenyl)porphine (TAc), as a biological photosensitizer has been evaluated both in vitro and in vivo in mitochondria from the R3230AC mammary tumor. Studies in vitro, consisting of incubation of mitochondria with TAc at a concentration of 4.0 micrograms/ml followed by photolysis, result in the inhibition of cytochrome c oxidase, proton translocating ATPase, succinate dehydrogenase, and malate dehydrogenase. The diminution in activity of the first three enzymes is approximately 2-fold greater than that seen with Photofrin II under the same conditions. Although TAc exists as four isolable atropisomers, no differences among these different forms were observed in their photosensitized inhibition of mitochondrial enzymes. Administration to tumor-bearing rats of TAc i.p. at a dose of 25 mg/kg did result in accumulation of porphyrin within the mitochondria of the R3230AC tumor as determined by subsequent irradiation of isolated mitochondria. The potential utility of TAc and related porphyrins in cancer phototherapy is discussed.
Cancer Res 1988 Mar 01
PMID:Picket-fence porphyrins as potential phototherapeutic agents. 283 16

Chemosensitivity to six different types of antitumor drugs was assayed using the succinate dehydrogenase inhibition (SDI) test, with regard to effects of 29 tissues from primary hepatocellular carcinomas (PHC) and 12 metastatic liver cancers. Succinate dehydrogenase activity in the PHC was significantly decreased by adriamycin (ADM), mitomycin C (MMC), aclacinomycin A (ACR) (P less than 0.01), and 5-fluorouracil (5-FU), cisplatin (DDP) and carboquone (CQ) (P less than 0.05), as compared to findings in tissues from the metastatic liver tumors. In PHC, chemosensitivity to antitumor drugs in the SDI test was positive in 58.6% of tissues exposed to ADM, 60.7% with MMC, 11.1% with 5-FU, 65.4% with DDP, 65.5% with ACR and 64.3% with CQ. On the contrary, the positive rates seen in metastatic liver tissues were 18.2% in DDP and 8.3% in CQ, and there was no positive chemosensitivity in tissues exposed to ADM, MMC, 5-FU and ACR. Therefore, PHC will show a better response than metastatic liver cancers to antitumor drugs. Our observations show that the selection of sensitive drugs is most important to improve the response rate and the survival time of patients. The SDI test proves useful for planning clinical management.
Eur J Cancer Clin Oncol 1988 Sep
PMID:Sensitivity to six antitumor drugs differs between primary and metastatic liver cancers. 284 13

The nephrotoxic potential of cis-diamminedichloroplatinum(II) (CDDP) in rabbits, as well as its effect on cell viability, cellular synthetic activity, and specific enzyme activities in rabbit renal proximal tubule cells, was investigated. Male New Zealand White rabbits were given a single i.v. dose of either 2.5 or 5.0 mg/kg CDDP via the ear vein and sacrificed 5 days later. No drug-induced changes were observed in the kidneys of rabbits given 2.5 mg/kg CDDP. However, histopathological examination of kidneys from rabbits administered 5.0 mg/kg CDDP revealed marked tubular degeneration and necrosis, with the majority of lesions being situated in the outer zone of the cortex. This is in contrast to the effect of CDDP in the kidney of the rat where the necrosis is reported to be predominantly localized to the pars recta of the proximal tubule in the outer stripe of the medulla. The results from the in vitro experiments indicated that the viability of cells after a 6-h exposure to CDDP at concentrations up to 100 microM was greater than 95%. However, a dose-dependent decrease in cell viability was obtained after 24 h exposure with a TD50 (50% viability) of approximately 90 microM. In addition, the results after 24 h exposure to CDDP also indicated that Na+, K+-ATPase, a basolateral membrane marker enzyme, and alkaline phosphatase, a brush-border marker enzyme, were inhibited by 35-40% and 20%, respectively. No effect on succinic dehydrogenase, a mitochondrial marker enzyme, was obtained. Inhibition of all three marker enzymes was minimal at 6 h posttreatment. On the other hand, inhibition of DNA, RNA, and protein syntheses was evident as early as 6 h posttreatment with DNA (48-77%) and RNA (36-77%) syntheses being inhibited to a greater extent than protein synthesis (14-33%). These results demonstrate that inhibition of renal synthetic activity by CDDP, rather than its effect on enzyme activity, precedes the onset of cell lethality and may therefore be an important event in the initiation of CDDP-induced nephrotoxicity.
Cancer Res 1988 May 01
PMID:Effects of cis-diamminedichloroplatinum(II) on rabbit kidney in vivo and on rabbit renal proximal tubule cells in culture. 296 14

The succinate dehydrogenase inhibition (SDI) test and the adenosine triphosphate (ATP) assay, are both used for in vitro human tumor chemosensitivity testing. We exposed HeLa cells to various concentrations of mitomycin C for 1, 2 or 3 days and found that the decrease in number of viable cells correlated with that of succinate dehydrogenase (EC 1.3.99.1) activity and that of intracellular ATP level of the viable cells. In the dead cells, the ATP level was extensively decreased, but the succinate dehydrogenase activity remained at a level of 24% of that of mitomycin C-untreated viable cells, even on day 3. Thus, the ATP level better reflected the cell viability. In clinical situations, the succinate dehydrogenase activity and the ATP level are assayed in whole cells following exposure to anticancer drugs, therefore the activity remaining in the dead cells must be taken into consideration for the chemosensitive prediction with the SDI test, but not with the ATP assay. This higher sensitivity of the ATP assay will enable a more accurate prediction of cell viability.
Eur J Cancer Clin Oncol 1987 Mar
PMID:The ATP assay is more sensitive than the succinate dehydrogenase inhibition test for predicting cell viability. 310 21

The tumor lysis syndrome, consisting of severe hyperkalaemia, hyperphosphatemia and hypocalcemia, occurs after the effective induction chemotherapy of rapidly growing responsive tumors. The metabolic abnormalities are thought to be secondary to the release of intracellular products. For the purpose to examine quantitative relation between cellular potassium release and drug sensitivity, we compare the inhibition of valinomycin (K-ionophore)-induced-hyperpolarization (MPR Test) with that of succinate dehydrogenase activity (SDI test). Our present research revealed a high correlation of MPR test and SDI test, and suggested the significant association of drug sensitivity with potassium release from cancer cells. Therefore, it seems appropriate to monitor potassium levels when therapy of a responsive tumor is initiated.
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PMID:[Drug sensitivity and cellular potassium release of cancer cells]. 317 38


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