irinotecan active metabolite sn 38  (TargetMol)

Journal: Frontiers in Pharmacology

Article Title: Apigenin directly interacts with and inhibits topoisomerase 1 to upregulate CD26/DPP4 on colorectal carcinoma cells

doi: 10.3389/fphar.2022.1086894

Figure Lengend Snippet: Neither CK2 inhibition, nor use of the apigenin metabolite luteolin, reproduce the interaction with apigenin seen with irinotecan. (A) The CK2 inhibitor emodin does not enhance the upregulation of CD26 by irinotecan. HT-29 cells were treated with irinotecan in the absence or presence of emodin (20 µM) as indicated, and cell-surface CD26 was assessed 48 h afterward. Data are means ± SEM ( n = 4); * p < 0.05, ** p < 0.01, enhancement by emodin; n.s., not significant; # p < 0.05 and ### p < 0.001 enhancement by irinotecan. (B) Luteolin enhances cell-surface CD26 in a dose-dependent manner. Means ± SEM ( n = 4); * p < 0.05, ** p < 0.01 and *** p < 0.001. (C) Luteolin does not enhance the upregulation of CD26 by irinotecan. Means ± SEM ( n = 4); ** p < 0.01, enhancement by luteolin (30 µM); n.s., not significant; ## p < 0.01 and ### p < 0.001 enhancement by irinotecan.

Article Snippet: Bovine serum albumin (BSA), dimethyl sulfoxide (DMSO), apigenin, luteolin (3′,4′,5,7-tetrahydroxyflavone), 6-methyl-1,3,8-trihydroxyanthraquinone (emodin), and the irinotecan active metabolite SN-38 (7-Ethyl-10-hydroxycamptothecin) were obtained from Sigma-Aldrich (St. Louis, MO.

Techniques: Inhibition

Journal: Frontiers in Pharmacology

Article Title: Apigenin directly interacts with and inhibits topoisomerase 1 to upregulate CD26/DPP4 on colorectal carcinoma cells

doi: 10.3389/fphar.2022.1086894

Figure Lengend Snippet: Topoisomerase 2 inhibitors elevate CD26 but do not reproduce the interaction with apigenin. (A,B) Topoisomerase 1 and 2 inhibitors both enhance cell-surface CD26. HT-29 cells treated for 48 h. Means ± SE ( n = 4), one-way ANOVA followed by Dunnett’s test; * p < 0.05 and ** p < 0.01, enhancement in CD26 by topoisomerase inhibitors. (C) Apigenin does not enhance the action or potency of etoposide. Means + SE ( n = 4); * p < 0.05, enhancement by apigenin (30 µM); ### p < 0.001 up-regulation by etoposide. (D) Apigenin interacts solely with the Topo1 inhibitor irinotecan. Means + SE ( n = 4); * p < 0.05, *** p < 0.01 enhancement by apigenin (30 µM); ### p < 0.001 up-regulation by topoisomerase inhibitors. Concentrations are: Irinotecan, 2 μg/ml; doxorubicin, 1 μg/ml; etoposide, 10 μg/m.

Article Snippet: Bovine serum albumin (BSA), dimethyl sulfoxide (DMSO), apigenin, luteolin (3′,4′,5,7-tetrahydroxyflavone), 6-methyl-1,3,8-trihydroxyanthraquinone (emodin), and the irinotecan active metabolite SN-38 (7-Ethyl-10-hydroxycamptothecin) were obtained from Sigma-Aldrich (St. Louis, MO.

Techniques:

Journal: Cancer letters

Article Title: Synergistic efficacy of irinotecan and sunitinib combination in preclinical models of anaplastic thyroid cancer

doi: 10.1016/j.canlet.2017.09.032

Figure Lengend Snippet: Antiproliferative effects of sunitinib (SU) and SN-38 in vitro on 8305C (A and C, respectively), and FB3 (B and D, respectively) cell lines. The antiproliferative effects of the drugs were studied after 72 h of exposure. The data are presented as percentage of vehicle-treated cells. The concentrations of drug that reduced cell proliferation by 50% (IC50) vs controls were calculated by a nonlinear regression fit of the mean values of the data obtained in triplicate experiments (i.e. at least 9 wells for each concentration). Columns and bars, mean values ± S.E., respectively. *, P < 0.001 vs. control.

Article Snippet: SN-38, the active metabolite of irinotecan, and sunitinib, were purchased from Selleckchem (DBA Italia, Milan, Italy), and dissolved in a stock solution of 10 mM in 100% dimethylsulfoxide (DMSO) for in vitro studies.

Techniques: In Vitro, Concentration Assay

Journal: Cancer letters

Article Title: Synergistic efficacy of irinotecan and sunitinib combination in preclinical models of anaplastic thyroid cancer

doi: 10.1016/j.canlet.2017.09.032

Figure Lengend Snippet: A) Apoptosis in primary ATC cells treated with sunitinib (SU) for 24 h (mean ± SD n = 5). Data were analyzed by one-way ANOVA with Newman–Keuls multiple comparisons test and with a test for linear trend (*P < 0.001 vs. control). The percentage of apoptotic cells after the treatment with vehicle (DMSO) was not significantly different from the one of control (not treated cells). B) Representative images of immunofluorescence Annexin V staining of sunitinib (SU) treated-cells. C) Pro-apoptotic effects of sunitinib (SU) and SN-38, alone or in combination, on proliferating FB3 cells treated for 72 h under hypoxic conditions (1% O2, 5% CO2, 95% humidity). All the absorbance values were plotted as a percentage of apoptosis relative to control cells (vehicle only), which is labelled as 100%. Columns and bars, mean values ± S.E., respectively. *P < 0.01 vs. vehicle-treated controls.

Article Snippet: SN-38, the active metabolite of irinotecan, and sunitinib, were purchased from Selleckchem (DBA Italia, Milan, Italy), and dissolved in a stock solution of 10 mM in 100% dimethylsulfoxide (DMSO) for in vitro studies.

Techniques: Immunofluorescence, Staining

Journal: Cancer letters

Article Title: Synergistic efficacy of irinotecan and sunitinib combination in preclinical models of anaplastic thyroid cancer

doi: 10.1016/j.canlet.2017.09.032

Figure Lengend Snippet: CI (Combination Index) and DRI (Dose Reduction Index) values for the drug combinations at 25%, 50%, and 75% levels of inhibition of 8305C and FB3 cell proliferation. SN-38, active metabolite of irinotecan; SU, sunitinib.

Article Snippet: SN-38, the active metabolite of irinotecan, and sunitinib, were purchased from Selleckchem (DBA Italia, Milan, Italy), and dissolved in a stock solution of 10 mM in 100% dimethylsulfoxide (DMSO) for in vitro studies.

Techniques: Inhibition

Journal: Cancer letters

Article Title: Synergistic efficacy of irinotecan and sunitinib combination in preclinical models of anaplastic thyroid cancer

doi: 10.1016/j.canlet.2017.09.032

Figure Lengend Snippet: Accumulation of SN-38 (ng · mg−1 protein) in 8305C (A) and FB3 (B) cell lines after exposure to 1 μM SN-38 alone and in combination with sunitinib (SU). Columns and bars indicate the mean percentage values (±S.D.) vs. treated cells with SN-38 alone. ABCG2 gene expression (2−ΔΔCt) and ABCG2 (ng · mg−1 protein) protein levels in 8305C (C and E, respectively) and FB3 (D and F, respectively) cells exposed to sunitinib or with vehicle alone for 72 h. Data are expressed as percentage of vehicle-treated cells. Columns and bars, mean values ± S.D., respectively. *P < 0.05 vs. vehicle-treated controls. The quantitation of gene expression was performed using the ΔΔCt calculation, where Ct is the threshold cycle; the amount of target, normalized to the endogenous control, glyceraldehyde 3-phosphate dehydrogenase, and relative to the calibrator (vehicle treated control cells), is given as 2−ΔΔCt. The quantitation of protein levels was performed by ELISA. The optical density was determined using a Multiskan Spectrum microplate reader set to 450 nm. The results were expressed as nanograms of ABCG2 per milligram of total protein. All experiments were repeated, independently, three times.

Article Snippet: SN-38, the active metabolite of irinotecan, and sunitinib, were purchased from Selleckchem (DBA Italia, Milan, Italy), and dissolved in a stock solution of 10 mM in 100% dimethylsulfoxide (DMSO) for in vitro studies.

Techniques: Expressing, Quantitation Assay, Enzyme-linked Immunosorbent Assay

Journal: Cancer letters

Article Title: Synergistic efficacy of irinotecan and sunitinib combination in preclinical models of anaplastic thyroid cancer

doi: 10.1016/j.canlet.2017.09.032

Figure Lengend Snippet: In vivo antitumor effects of the single drugs and three different combination schedules of sunitinib (SU) and irinotecan (CPT-11) on 8305C tumors xenotransplanted in mice (A); Immunohistochemistry quantification of CD31 (B) and Capase-3 positive cells (C) in 8305C tumor xenografts administered with vehicle, SU at 25 mg/kg every 3 days, CPT-11 100 mg/kg every week through i.p. injection, and their combinations. Symbols/columns and bars, mean values ± S.D., respectively.*P < 0.001 vs. vehicle-treated controls. #P < 0.001 vs. sunitinib-treated group.

Article Snippet: SN-38, the active metabolite of irinotecan, and sunitinib, were purchased from Selleckchem (DBA Italia, Milan, Italy), and dissolved in a stock solution of 10 mM in 100% dimethylsulfoxide (DMSO) for in vitro studies.

Techniques: In Vivo, Immunohistochemistry, Injection