Criteria for Analyzing Interactions between Biologically Active Agents

Berenbaum, M. C.

doi:10.1016/s0065-230x(08)60912-4

Cited by 402 publications

(248 citation statements)

References 74 publications

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“…Treatment with tyrphostins as single agents revealed an IC 50 for inhibition of cell proliferation of 3.7570.8 mM for AG 1024, and 21.573.3 mM for AG 1296. These two inhibitors were used in a matrix of combinations, and an isobologram plot (Berenbaum, 1981) for IC 50 demonstrated synergistic interactions in growth inhibition (Figure 2A). Combination index (CI) values for several combination treatments were calculated from the classic isobologram equation and proved significantly smaller than 1, indicating synergy.…”

Section: Resultsmentioning

confidence: 99%

“…Tests were conducted in triplicates with 10 4 cells treated with tyrphostins singly or in combination for a total of 72 h in RPMI with 1% FBS, and proliferation of the anchorageindependent cells was assayed by Alamar blue dye reduction (shown is an experiment representative of five). Proliferation CI values were calculated using the classic isobologram equation (Berenbaum, 1981) and are indicated on a graph. CI values o1 indicate synergy.…”

Section: Discussionmentioning

confidence: 99%

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Co-targeting IGF-1R and c-kit: synergistic inhibition of proliferation and induction of apoptosis in H 209 small cell lung cancer cells

Camirand

Pollak

2004

Br J Cancer

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Most small cell lung cancers (SCLC) coexpress the c-kit protein tyrosine receptor kinase and its ligand stem cell factor, resulting in an autocrine loop. As SCLC growth is also driven by insulin-like growth factor-1 receptor (IGF-1R) signalling, tyrphostins AG 1024 and 1296 (inhibitors of IGF-1R and c-kit activity, respectively) were used to co-target these receptors in H 209 SCLC cells. Combination treatment caused synergy in proliferation inhibition and in apoptosis induction, and also enhanced reduction in phosphorylation of Erk1/Erk2, suggesting that co-targeting IGF-1R and c-kit in SCLC may be more effective than single-agent therapies.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Co-targeting IGF-1R and c-kit: synergistic inhibition of proliferation and induction of apoptosis in H 209 small cell lung cancer cells

Camirand

Pollak

2004

Br J Cancer

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“…Synergistic interaction between BA and VCR was determined by using isobologram analysis as described in detail previously (Berenbaum, 1981;Sora et al, 1994). Briefly, inhibition of cell proliferation was determined as described above.…”

Section: Drug Interaction Analysismentioning

confidence: 99%

“…To clarify the synergistic effect of VCR and BA on inhibition of the growth of B16F10 cells, we used isobologram analysis by the method of Berenbaum (1981). Treatment with VCR or BA resulted in inhibition of the growth of B16F10 cells in a dose-dependent manner (Figure 5a and b).…”

Section: Induction Of Apoptosis In B16f10 Cells By Vcr and Bamentioning

confidence: 99%

Betulinic acid augments the inhibitory effects of vincristine on growth and lung metastasis of B16F10 melanoma cells in mice

et al. 2004

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We examined the antitumour effect of a combination of betulinic acid (BA) and vincristine (VCR) on murine melanoma B16F10 cells in vitro and in vivo. Betulinic acid, a pentacyclic triterpene, showed a synergistic cytotoxic effect on melanoma cells by combinational use of VCR. Betulinic acid and VCR induced cell cycle arrest at different points (BA at G1 phase and VCR at G2/M phase) and caused apoptosis in B16F10 melanoma cells. In the in vivo study, VCR inhibited metastasis of tumour cells to the lung. The addition of BA to VCR augmented suppression of the experimental lung metastasis of melanoma cells in C57BL/6 mice. The number of lung nodules of more than 1 mm in diameter in mice treated with BA and VCR was less than that in mice treated with VCR alone. These results suggest that BA is an effective supplement for enhancing the chemotherapeutic effect on malignant melanoma.

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“…The characteristics of the combined treatment were then analysed by the isobole method (Berenbaum, 1981) analysing the equation Ac/Ae + Bc/Be = D, where Ac and Bc correspond to concentrations of drugs A and B used in the combined treatment, and Ae and Be are the concentrations of drugs able to produce the same magnitude of effect if used individually. If D (combination index) < 1, the effect of combination is synergistic, when D = 1 its effect is additive and in the case of D > 1 the combined action is antagonistic.…”

Section: Growth Inhibition Experimentsmentioning

confidence: 99%

Sodium phenylacetate enhances the inhibitory effect of dextran derivative on breast cancer cell growth in vitro and in nude mice

et al. 2001

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Summary Sodium phenylacetate (NaPa) and carboxymethyl benzylamide dextran derivative (CMDB LS4 ) are able to inhibit growth of breast tumour cells. In this study, we explored whether the combination of NaPa and CMDB LS4 may enhance their respective inhibitory effects on the MCF-7ras cell growth in vitro and in vivo. NaPa inhibited MCF-7ras cell proliferation by reducing the DNA replication concomitantly with a recruitment of cells in G0/G1 phase and by inducing apoptosis in a dose-and time-dependent manner. The addition of CMDB LS4 potentiated the NaPa antiproliferative effect in the manner dependent on the ratio of CMDB LS4 and NaPa concentrations. In nude mice, CMDB LS4 (150 mg kg -1 ) or NaPa (40 mg kg -1 ) administrated twice a week, for 7 weeks inhibited MCF-7ras xenograft growth by 40% and 60%, respectively. The treatment by both, CMDB LS4 and NaPa, decreased tumour growth by 83% without any toxicity. To better understand the mechanism of NaPa and CMDB LS4 action we assessed their effect on mitogenic activity of MCF-7ras conditioned medium (CM) on BALBC/3T3 fibroblasts. CMDB LS4 added to the CM, inhibited its mitogenic activity whereas NaPa had an anti-mitogenic effect when CM was prepared from MCF-7ras cells pretreated with NaPa. Thus, the antiproliferative effects of NaPa and CMDB LS4 involve 2 different mechanisms explaining, at least in part, the possible synergism between them. Overall, this study points to the potential use of a combination of dextran derivatives with NaPa to inhibit the breast tumour growth.

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Criteria for Analyzing Interactions between Biologically Active Agents

Cited by 402 publications

References 74 publications

Co-targeting IGF-1R and c-kit: synergistic inhibition of proliferation and induction of apoptosis in H 209 small cell lung cancer cells

Co-targeting IGF-1R and c-kit: synergistic inhibition of proliferation and induction of apoptosis in H 209 small cell lung cancer cells

Betulinic acid augments the inhibitory effects of vincristine on growth and lung metastasis of B16F10 melanoma cells in mice

Sodium phenylacetate enhances the inhibitory effect of dextran derivative on breast cancer cell growth in vitro and in nude mice

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