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Biomedical subjects

M Suganuma

Publications and source records attributed to M Suganuma.

At least 127 records · Page 7Linked to original sources
PubMed1987

Presence of tumor promoters in the seed oil of Jatropha curcas L. from Thailand.

The seed oil of Jatropha curcas L. was shown to contain skin tumor promoters in a two-stage mouse carcinogenesis experiment. By using the irritant test on mouse ear to monitor activity, the "irritant fraction" was partially purified from the methanol extract of the seed oil by column chromatographies on Florisil and Sephadex LH-20. The irritant fraction obtained induced ornithine decarboxylase in mouse skin and inhibited the specific binding of 3H-12-O-tetradecanoylphorbol-13-acetate to a particulate fraction of mouse skin. After initiation with 7,12-dimethylbenz[a]anthracene (DMBA), this "irritant fraction" induced tumors in the skin of 36% of the mice tested in 30 weeks. Tumor incidences in the groups treated with DMBA alone and "irritant fraction" alone were 7% and 13% in week 30, respectively. Since the skin of Thai people comes into direct contact with this seed oil, an epidemiological study on human skin cancer in Thailand is indicated.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1987

Synthetic analogues (indolactams) of (-)-indolactam-V are new congeners of the teleocidin class of tumor promoters.

(-)-Indolactam-V, which has the partial structure of teleocidins A and B, and has tumor-promoting activity, is a good model for use in studies on the relation between structure and tumor-promoting activity, whereas (+)-indolactam-V has no tumor-promoting activity. In this work, five racemic indolactams differing only in their alkyl group at C-12 of (-)-indolactam-V were synthesized and tested for biological and biochemical activities related to tumor promotion. The activities tested were inductions of ornithine decarboxylase in mouse skin and human promyelocytic leukemia (HL-60) cell adhesion, inhibition of specific [3H]12-O-tetradecanoyl-phorbol-13-acetate binding to a mouse particulate fraction and activation of protein kinase C in vitro. The results showed that (+/-)-indolactam-L and (+/-)-indolactam-F had almost the same activities as (+/-)-indolactam-V, suggesting that (-)-indolactam-L and (-)-indolactam-F are new tumor promoters with as high potency as (-)-indolactam-V. (+/-)-Indolactam-t-L, which has a highly lipophilic group at C-12 of (-)-indolactam-V, showed the highest activities in the above tests. (-)-Indolactam-t-L might have stronger tumor-promoting activity than (-)-indolactam-V. Furthermore, the results with (-)-indolactam-t-L indicated the possibility of designing new tumor promoters with stronger activity than teleocidin.

Animals↗
PubMed1986

Involvement of sulfatide in activation of protein kinase C by tumor promoters.

Sulfatide (cerebroside sulfate) activated protein kinase C to the same extent as phosphatidylserine did with the tumor promoters, 12-O-tetradecanoylphorbol-13-acetate (TPA), teleocidin and debromoaplysiatoxin. Sulfatide and phosphatidylserine both induced specific binding of [3H]TPA to protein kinase C, although the ratios of specific to non-specific [3H]TPA binding to protein kinase C with the two were not the same. It is concluded that sulfatide is involved in activation of protein kinase C by tumor promoters in a slightly different way from phosphatidylserine.

Animals↗
PubMed1986

Synergistic stimulation of histamine release from rat peritoneal mast cells by 12-O-tetradecanoylphorbol 13-acetate (TPA)-type and non-TPA-type tumor promoters.

Thapsigargin, a non-TPA (12-O-tetradecanoylphorbol 13-acetate)-type tumor promoter, provoked histamine release from rat peritoneal mast cells at concentrations above 30 ng/ml, but not at 10 ng/ml. TPA-type tumor promoters such as TPA, teleocidin and aplysiatoxin released very little, if any, histamine even at 100 ng/ml. When mast cells were incubated in medium containing thapsigargin at 10 ng/ml and varying concentrations of TPA-type tumor promoters, histamine release was increased synergistically. Maximum synergistic effects were observed at 10 ng/ml of each TPA-type tumor promoter. Palytoxin, another non-TPA-type tumor promoter, having no effect on histamine release at up to 10 pg/ml, also induced histamine release in the presence of 10 ng/ml of each TPA-type tumor promoter. However, no synergistic effect on histamine release was observed when mast cells were incubated in medium containing two different non-TPA-type tumor promoters, e.g., 10 ng/ml thapsigargin and 10 pg/ml palytoxin, or in medium containing two different TPA-type tumor promoters, e.g., TPA and teleocidin, TPA and aplysiatoxin, or teleocidin and aplysiatoxin (all at 10 ng/ml). These results suggest that the release of histamine from mast cells is stimulated synergistically under the mutual influence of TPA-type tumor promoters and non-TPA-type tumor promoters.

Animals↗
PubMed1986

Thapsigargin, a histamine secretagogue, is a non-12-O-tetradecanoylphorbol-13-acetate (TPA) type tumor promoter in two-stage mouse skin carcinogenesis.

Thapsigargin, a hexaoxygenated tetraacylated sesquiterpene lactone, induced irritation of mouse ear and histidine decarboxylase (HDC) activity in mouse skin, but it did not induce ornithine decarboxylase in mouse skin or adhesion of human promyelocytic leukemia (HL-60) cells. Although thapsigargin did not give consistent positive results in a short-term screening system for tumor promoters, it was tested in a two-stage carcinogenesis experiment on mouse skin. The potency of thapsigargin to induce HDC in mouse skin was used to determine the dose in this experiment. Application of 10 micrograms (17 nmol) thapsigargin induced HDC activity of 139 pmol CO2/mg protein per 60 min. Tumors were found in the skin of 53.5% of the mice treated with DMBA plus 5 micrograms (8.5 nmol) thapsigargin in week 22, in none of those treated with thapsigargin alone by week 30. One tumor appeared in 1 of 15 mice treated with DMBA alone in week 21. Thapsigargin cannot bind to the phorbol ester receptor in the particulate fraction of mouse skin and so is classified as a non-12-O-tetradecanoylphorbol-13-acetate (TPA) type tumor promoter. It is a new tumor promoter differing in many respects from the well-defined TPA type tumor promoters. Several naturally occurring analogues of thapsigargin, such as thapsigargicin and thapsitranstagin, might also be new non-TPA type tumor promoters, because thapsigargicin and thapsitranstagin induced irritation of mouse ear and HDC activity in mouse skin.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1986

Binding studies of [3H]lyngbyatoxin A and [3H]debromoaplysiatoxin to the phorbol ester receptor in a mouse epidermal particulate fraction.

The preparation of [3H]lyngbyatoxin A by catalytic triton-proton exchange of lyngbyatoxin A and [3H]debromoaplysiatoxin by tritiation-debromination of aplysiatoxin is described. The dose-response curves for the binding of [3H]lyngbyatoxin A and [3H]debromoaplysiatoxin to a mouse epidermal particulate fraction are virtually the same as the one previously described for [3H]12-O-tetradecanoylphorbol-13-acetate ([3H]TPA). The specific binding of [3H]TPA, [3H]-lyngbyatoxin A and [3H]debromoaplysiatoxin to the mouse epidermal particulate fraction is inhibited to the same degree by unlabeled TPA, teleocidin, lyngbyatoxin A, aplysiatoxin and debromoaplysiatoxin. This study indicates that TPA, lyngbyatoxin A and debromoaplysiatoxin bind to the same high affinity receptor in mouse skin.

Animals↗
PubMed1986

Palytoxin is a non-12-O-tetradecanoylphorbol-13-acetate type tumor promoter in two-stage mouse skin carcinogenesis.

Palytoxon, which is a toxin with a molecular weight of 2681 daltons isolated from a marine coelenterate, is a potent skin irritant. However, it did not induce ornithine decarboxylase in mouse skin, or adhesion of human promyelocytic leukemia cells (HL-60). Moreover, it did not inhibit the specific binding of [3H]12-O-tetradecanoylphorbol-13-acetate (TPA) to a mouse skin particulate fraction or activate protein kinase C isolated from mouse brain in vitro. Since palytoxin showed strong irritation on mouse ear in one short-term screening test for a promoter, it was examined in a two-stage carcinogenesis experiment. The incidence of tumors in a group of mice treated with 7,12-dimethylbenz[a]anthracene plus palytoxin was 62.5% in week 25. These tumors were identified histologically as seven papillomas and one carcinoma. This paper reports the potent tumor-promoting activity of palytoxin, which is classified as a non-TPA-type tumor promoter.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1986

Des-O-methylolivoretin C is a new member of the teleocidin class of tumor promoters.

Des-O-methylolivoretin C, a demethylated form of olivoretin C, is a naturally occurring compound in Streptomyces mediocidicus and Streptoverticillium olivoreticuli. Des-O-methylolivoretin C is a regioisomer of teleocidin B, which has the same activity as teleocidin. The tumor-promoting activity of des-O-methylolivoretin C was studied in a two-stage carcinogenesis experiment on mouse skin in comparison with that of teleocidin. Treatments with 7,12-dimethylbenz[a]anthracene (DMBA) plus des-O-methylolivoretin C and DMBA plus teleocidin induced tumors in 63.3% and 84.6% of the mice, respectively, in week 30. The difference in the tumor-promoting activities of des-O-methylolivoretin C and teleocidin is presumably related to the regioisomeric difference in the cyclohexene ring.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1986

Modulation of phorbol ester receptors in mouse skin by application of quercetin.

The topical application of quercetin, an anti-tumor promoter, to mouse skin reduced the number of phorbol ester receptors, although quercetin did not inhibit specific 3H-12-O-tetradecanoylphorbol-13-acetate binding to a mouse skin particulate fraction. Quercetin, morin, kaempferol and luteolin inhibited activation of protein kinase C by teleocidin, and caused half-maximal activation at 25 microM. (+)-Catechin, which has been reported not to inhibit tumor-promoting activity, did not have any effect on these reactions. The modulation of phorbol ester receptors and inhibition of activation of protein kinase C are considered to be involved in the anti-tumor-promoting effect of quercetin in mouse skin. Diet containing 4% or 1% quercetin did not influence the action of teleocidin on mouse skin in a two-stage carcinogenesis experiment.

Animals↗
PubMed1985

Stimulation of prostaglandin E2 production by 12-O-tetradecanoylphorbol 13-acetate (TPA)-type and non-TPA-type tumor promoters in macrophages and its inhibition by cycloheximide.

The effects of TPA (12-O-tetradecanoylphorbol 13-acetate)-type and non-TPA-type tumor promoters on prostaglandin E2 production by peritoneal macrophages of rats were examined. Among the TPA-type tumor promoters, aplysiatoxin was most potent in stimulating prostaglandin E2 production followed by dihydroteleocidin B, teleocidin, TPA and debromoaplysiatoxin. Prostaglandin E2 production by aplysiatoxin treatment was stimulated at doses up to 0.1 ng/ml. Palytoxin, a non-TPA-type tumor promoter, also stimulated both prostaglandin E2 production and the release of radioactivity from [3H]arachidonic acid-labeled macrophages. However, the dose required for the expression of these effects by palytoxin was up to 3 pg/ml. It was suggested that the tumor promoters are associated with the activity to stimulate arachidonic acid metabolism, irrespective of their type. Cycloheximide, a protein synthesis inhibitor, inhibited both prostaglandin E2 production and the release of radioactivity from prelabeled macrophages stimulated either by the TPA-type tumor promoters or by the non-TPA-type tumor promoter. It is possible that the tumor promoters may induce the synthesis of some proteins responsible for the stimulation of arachidonate metabolism.

Acrylamides↗
PubMed1985

A blue-green alga from Okinawa contains aplysiatoxins, the third class of tumor promoters.

The causative agents of swimmer's itch were isolated from the marine blue-green alga, Lyngbya majuscula, which grows off the coast of the Okinawa islands, Japan. Nuclear magnetic resonance and mass spectral studies revealed that these agents were identical with aplysiatoxin and debromoaplysiatoxin, which were previously shown to be the causative agents of swimmer's itch in Hawaii. Aplysiatoxin and debromoaplysiatoxin were recently found to be potent tumor promoters in two-stage carcinogenesis in mouse skin. This is the first report that humans are directly affected by these potent environmental tumor promoters in Japan.

Animals↗
PubMed1984

Reduction by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), a calmodulin antagonist, in the number of phorbol ester receptors in mouse skin.

A calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (W-7), reduced the number of phorbol ester receptors in mouse skin in a dose- and time-dependent manner. The reduction occurred immediately after topical application of 30 mumoles of W-7, reaching a maximum of 86% after 5 min. Reduction in specific binding of 12-O-tetra-decanoylphorbol-13-acetate can explain the antitumor promoting activity of W-7 in mouse skin.

Animals↗
PubMed1984

A two-stage mouse skin carcinogenesis study of lyngbyatoxin A.

A strong skin irritant, lyngbyatoxin A, isolated from the marine blue-green alga Lyngbya majuscula is structurally related to teleocidin. Since lyngbyatoxin A satisfied our short-term screening tests for possible tumor promoters, viz. irritation of mouse ear, induction of ornithine decarboxylase (ODC) in mouse skin, and adhesion of human promyelocytic leukemia cells (HL-60), a two-stage carcinogenesis experiment was carried out. Tumor incidences in the groups treated with 7,12-dimethylbenz(a)anthracene (DMBA) plus lyngbyatoxin A and with DMBA plus 12-O-tetradecanoylphorbol-13-acetate (TPA) were 86.7% and 93.3% in week 30, respectively. The average number of tumors per mouse was 3.7 in the former group and 10.5 in the latter group. This paper reports for the first time the potent tumor-promoting activity of lyngbyatoxin A and also the histological examination of tumors.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1984

Estimation of tumor promoting activity and structure-function relationships of aplysiatoxins.

Twelve aplysiatoxin compounds have been evaluated as possible tumor promoters in vivo by means of three biological tests: viz. irritation of mouse ear, induction of ornithine decarboxylase in dorsal skin of mice, and inhibition of specific binding of [3H]12-O-tetradecanoylphorbol-13-acetate (TPA) to an epidermal particulate fraction. The potencies of these three biological activities correlate well for each derivative. Bromoaplysiatoxin shows biological activities that are similar to those of the strong tumor promoter, aplysiatoxin. The present studies suggest that the C-3, C-20 and C-30 hydroxyl groups of the aplysiatoxins are involved in binding to the specific receptor of TPA.

Animals↗