トポイソメラーゼ

Enhancement of apoptotic response by addition of targeted agents lapatinib and sunitinib to doxorubicin in the same device reservoir at 24 hours. P values were determined using Student’s t test for all graphs.

ABT-199 synergizes strongly with lymphoma chemotherapy agents that affect MCL1 levels. Viability and CI vs Fa after 24-h exposure to etoposide alone or in combination with ABT-199 in Riva, U2932 and VavP-Bcl2/c-MYC murine tumor cells. Viability shown at 500 nM.

CtIP and exonuclease 1 protect cells from chromosomal damage. (A) At 72 h after transfection with the indicated siRNA oligonucleotides, U2OS cells were treated with either DMSO or camptothecin (1 h, 1 μM; acute treatment) and survival was determined by colony formation. Data represent the mean±s.e.m. of five independent experiments. (B) Cell survival at low doses of camptothecin from the data shown in (A). Data represent the mean±s.e.m. of five independent experiments. (C) Cells transfected as in (A) were treated with either DMSO or camptothecin for 24 h (chronic treatment) and survival was determined by colony formation. Data represent the mean±s.e.m. of three independent experiments. (D) Metaphase spreads from cells transfected and treated as described in (A) were analysed for chromosomal aberrations. A total of 50 metaphase spreads was analysed for each sample. The percentages of metaphase spreads displaying the indicated numbers of radial chromosomes are shown. CNTL, control; DMSO, dimethyl sulphoxide; EXO1, exonuclease 1; siRNA, small interfering RNA.

Cells were treated at the same concentrations as in Caspase3/7 assay for 16 hours and total cell lysates were prepared for Western blotting. GAPDH was used as a loading control.

Sensitivity of AML cells to conventional induction treatment and small-molecule p53 activators. Cell viability in OCI-AML3 cells treated for 24 hours with cytarabin/idarubicin (CI) and Nultin-3A (Nut; A), CI and Leptomycin-B (LMB; B), or Nut and LMB (D), respectively. CI was tested at 0, 100, 200, and 300 nmol/L CI; Nutlin-3A at 0, 2.5, 5, 7.5; and LMB at 0, 2, 8, 32 ng/mL in dosages 0, 1, 2, and 3, respectively. Cell viability in normal and AML bone marrow cells.

 

Growth inhibitory effects of Epirubicin human pancreatic cancer cells. MiaPaCa-2 cells were plated in triplicates into 48-well plates at a density of 10,000 cells/ml. After 24 hours, complete culture medium was changed into fresh low-serum-containing medium (0.5% FBS) containing DMSO (control) or indicated doses of Epirubicin (Selleckchem). Cell viability 48 hours after treatment was determined by AlamarBlue assay (Invitrogen) according to manufacturer's instructions. Results are expressed as percentages of control, which was arbitrarily assigned 100% viability, and represented as the mean ± standard deviation (SD) of the tripicate wells. 

Immunohistochemistry and quantification of cleaved caspase 3 expression in DU145-DR tumor xenografts from (D). Scale bar, 100 mm. Data represent the mean ± SD. *p < 0.05.

A) MV411 or B) Kasumi 1 cells were incubated with YM155 (0.25 x IC50) in the presence or absence of i) 0.5 x IC50 or ii) 1 x IC50 of Daunorubicin or iii) 0.5 x IC50 or iv) 1 x IC50 of Cytarabine for 72h. Following 72h treatment, cells were subject to a resazurin reduction assay. Percentages were normalised to DMSO controls. Column, mean of 3 independent experiments; Bars, SEM. *p<0.05, **p<0.01, ***p<0.005. Students t-test. Similar trends were observed with 0.5 x and 1 x IC50 of YM155 in combination with Daunorubicin or Cytarabine (data not shown).

In vitro cell uptake data showing the HA coating on HAC-PFP-DC nanoparticles significantly improves drug delivery into prostasphere and mammosphere cells enriched with CSCs. Fluorescence micrographs of (A) prostasphere and (B) mammosphere cells after incubated with the simple mixture of free DOX&CPT, PFP-DC nanoparticles, and HAC-PFP-DC nanoparticles for 3 h at 37 °C. CPT:irinotecan

CRC lung metastasis was established after iv injection of HT-29 LuM3 cells (1.5×106 cells in 100 μl of PBS). The polymeric nanoparticles loaded with PX866 and SN-38 were administered iv 72h after HT-29 LuM3 cells injection every q24h for 4 days and continued every q72h for 26 days (10 μg/g dose in 300 μl of PBS). PX866+SN−38 combination treatment was administered iv 72h after HT-29 LuM3 cells injection every q24h for 4 days (10 μg/g PX866 + 10 μg/g SN-38 mixed in 300 μl of PBS). Control: Empty PNP. Green: GFP expressing HT-29 LuM3 cells.

Cleavable complex formation with nuclear DNA in P. falciparum treated with topoisomerase poisons. Parasites were metabolically labeled with [3H]hypoxanthine, treated with etoposide (■), gatifloxacin (●), levofloxacin(▲), ciprofloxacin (□), fleroxacin (○), or nalidixic acid (△) at the indicated concentrations for 18-22 h, lysed with SDS and digested with RNases. SDS and protein-bound DNA were precipitated with potassium. The fold increase in nuclear DNA capture as compared to solvent controls (mean of triplicate determinations) was plotted against concentration. Coefficient of variation for each data point was 19%.

Ciprofoxacin (Cipro) reduces cancer cell survival in combination with chemotherapy. A and B, colony formation was conducted with A549 and SW48 cells treated with the clinically relevant chemotherapeutics cisplatin or 5-FU in the presence or absence of 2 μmol/L cipro floxacin. C, cipro fl oxacin at 2 μmol/L decreased proliferation of KG-1 cells and slightly enhanced the effect of etoposide (Etop). *, P < 0.05; **, P < 0.01 ( t tests).

Cell viability and caspase 3/7 activity in MDA-MB-231 cells co-treated with carbenoxolone, novobiocin, ibrutinib and bisphosphonates. Cell viability (A) and caspase 3/7 activity (B) was determined after treatment with ZA (zoledronic acid), RIS (risedronate), IBN (ibandronate), ALN (alendronate) in combination with carbenoxolone, novobiocin and ibrutinib. All data are expressed as means of three different measure points of three independent experiments ± SEM and were normalized to BP treatment alone. Significances were calculated with the Mann Whitney U test (*p < 0.05; **p < 0.005).

Enhancement of apoptotic response by addition of targeted agents lapatinib and sunitinib to doxorubicin in the same device reservoir at 24 hours. P values were determined using Student’s t test for all graphs.

ABT-199 synergizes strongly with lymphoma chemotherapy agents that affect MCL1 levels. Viability and CI vs Fa after 24-h exposure to etoposide alone or in combination with ABT-199 in Riva, U2932 and VavP-Bcl2/c-MYC murine tumor cells. Viability shown at 500 nM.

CtIP and exonuclease 1 protect cells from chromosomal damage. (A) At 72 h after transfection with the indicated siRNA oligonucleotides, U2OS cells were treated with either DMSO or camptothecin (1 h, 1 μM; acute treatment) and survival was determined by colony formation. Data represent the mean±s.e.m. of five independent experiments. (B) Cell survival at low doses of camptothecin from the data shown in (A). Data represent the mean±s.e.m. of five independent experiments. (C) Cells transfected as in (A) were treated with either DMSO or camptothecin for 24 h (chronic treatment) and survival was determined by colony formation. Data represent the mean±s.e.m. of three independent experiments. (D) Metaphase spreads from cells transfected and treated as described in (A) were analysed for chromosomal aberrations. A total of 50 metaphase spreads was analysed for each sample. The percentages of metaphase spreads displaying the indicated numbers of radial chromosomes are shown. CNTL, control; DMSO, dimethyl sulphoxide; EXO1, exonuclease 1; siRNA, small interfering RNA.

Cells were treated at the same concentrations as in Caspase3/7 assay for 16 hours and total cell lysates were prepared for Western blotting. GAPDH was used as a loading control.

Sensitivity of AML cells to conventional induction treatment and small-molecule p53 activators. Cell viability in OCI-AML3 cells treated for 24 hours with cytarabin/idarubicin (CI) and Nultin-3A (Nut; A), CI and Leptomycin-B (LMB; B), or Nut and LMB (D), respectively. CI was tested at 0, 100, 200, and 300 nmol/L CI; Nutlin-3A at 0, 2.5, 5, 7.5; and LMB at 0, 2, 8, 32 ng/mL in dosages 0, 1, 2, and 3, respectively. Cell viability in normal and AML bone marrow cells.

 

Growth inhibitory effects of Epirubicin human pancreatic cancer cells. MiaPaCa-2 cells were plated in triplicates into 48-well plates at a density of 10,000 cells/ml. After 24 hours, complete culture medium was changed into fresh low-serum-containing medium (0.5% FBS) containing DMSO (control) or indicated doses of Epirubicin (Selleckchem). Cell viability 48 hours after treatment was determined by AlamarBlue assay (Invitrogen) according to manufacturer's instructions. Results are expressed as percentages of control, which was arbitrarily assigned 100% viability, and represented as the mean ± standard deviation (SD) of the tripicate wells. 

Immunohistochemistry and quantification of cleaved caspase 3 expression in DU145-DR tumor xenografts from (D). Scale bar, 100 mm. Data represent the mean ± SD. *p < 0.05.

A) MV411 or B) Kasumi 1 cells were incubated with YM155 (0.25 x IC50) in the presence or absence of i) 0.5 x IC50 or ii) 1 x IC50 of Daunorubicin or iii) 0.5 x IC50 or iv) 1 x IC50 of Cytarabine for 72h. Following 72h treatment, cells were subject to a resazurin reduction assay. Percentages were normalised to DMSO controls. Column, mean of 3 independent experiments; Bars, SEM. *p<0.05, **p<0.01, ***p<0.005. Students t-test. Similar trends were observed with 0.5 x and 1 x IC50 of YM155 in combination with Daunorubicin or Cytarabine (data not shown).

In vitro cell uptake data showing the HA coating on HAC-PFP-DC nanoparticles significantly improves drug delivery into prostasphere and mammosphere cells enriched with CSCs. Fluorescence micrographs of (A) prostasphere and (B) mammosphere cells after incubated with the simple mixture of free DOX&CPT, PFP-DC nanoparticles, and HAC-PFP-DC nanoparticles for 3 h at 37 °C. CPT:irinotecan

CRC lung metastasis was established after iv injection of HT-29 LuM3 cells (1.5×106 cells in 100 μl of PBS). The polymeric nanoparticles loaded with PX866 and SN-38 were administered iv 72h after HT-29 LuM3 cells injection every q24h for 4 days and continued every q72h for 26 days (10 μg/g dose in 300 μl of PBS). PX866+SN−38 combination treatment was administered iv 72h after HT-29 LuM3 cells injection every q24h for 4 days (10 μg/g PX866 + 10 μg/g SN-38 mixed in 300 μl of PBS). Control: Empty PNP. Green: GFP expressing HT-29 LuM3 cells.

Cleavable complex formation with nuclear DNA in P. falciparum treated with topoisomerase poisons. Parasites were metabolically labeled with [3H]hypoxanthine, treated with etoposide (■), gatifloxacin (●), levofloxacin(▲), ciprofloxacin (□), fleroxacin (○), or nalidixic acid (△) at the indicated concentrations for 18-22 h, lysed with SDS and digested with RNases. SDS and protein-bound DNA were precipitated with potassium. The fold increase in nuclear DNA capture as compared to solvent controls (mean of triplicate determinations) was plotted against concentration. Coefficient of variation for each data point was 19%.

Ciprofoxacin (Cipro) reduces cancer cell survival in combination with chemotherapy. A and B, colony formation was conducted with A549 and SW48 cells treated with the clinically relevant chemotherapeutics cisplatin or 5-FU in the presence or absence of 2 μmol/L cipro floxacin. C, cipro fl oxacin at 2 μmol/L decreased proliferation of KG-1 cells and slightly enhanced the effect of etoposide (Etop). *, P < 0.05; **, P < 0.01 ( t tests).

Cell viability and caspase 3/7 activity in MDA-MB-231 cells co-treated with carbenoxolone, novobiocin, ibrutinib and bisphosphonates. Cell viability (A) and caspase 3/7 activity (B) was determined after treatment with ZA (zoledronic acid), RIS (risedronate), IBN (ibandronate), ALN (alendronate) in combination with carbenoxolone, novobiocin and ibrutinib. All data are expressed as means of three different measure points of three independent experiments ± SEM and were normalized to BP treatment alone. Significances were calculated with the Mann Whitney U test (*p < 0.05; **p < 0.005).