Table 1.
Fifty percent inhibitory concentration (IC50) and combination index (CI) of Clarithromycin, Irinotecan, 5-Fluorouracil, Cisplatin, and Oxaliplatin for the reported cancer cell lines.
| (a) IC50 values of Clarithromycin for different cell lines | ||||
|---|---|---|---|---|
| Drug | Cell line | IC50 (μM) | ||
| Clarithromycin | ||||
| HCT116 | 80.0 ± 2.0 | |||
| HT29 | 125.3 ± 16.8 | |||
| LS174T | 154.4 ± 9.1 | |||
| HCT116 p53−/− | 150.0 ± 8.6 | |||
| HEK293 | >200 | |||
| HEK293-MOCK | >200 | |||
| HEK293-hERG1 | 92.4 ± 4.9 | |||
| (b) IC50 and IC25 values of Irinotecan (CPT11), 5-Fluorouracil (5-FU), Cisplatin (Cis), and Oxaliplatin (Oxa), and their combination index (CI) with Clarithromycin for HCT116 cells | ||||
| Drug | IC50 (μM) | IC25 (μM) | CI at IC50 (effect) | CI at IC25 (effect) |
| CPT-11 | 10.1 ± 2.1 | 2.1 ± 0.1 | 0.63 ± 0.09 (S) | 0.41 ± 0.02 (S) |
| 5-FU | 13.7 ± 2.4 | 2.21 ± 0.1 | 0.57 ± 0.07 (S) | 0.38 ± 0.03 (S) |
| Cis | 25.2 ± 2.1 (Ref. 50) | 9.04 ± 0.7 | 1.38 ± 0.06 (A) | 0.87 ± 0.15 (S) |
| Oxa | 57.4 ± 9.4 (Ref. 50) | 12.2 ± 3.0 | 1.10 ± 0.11 (A) | 0.78 ± 0.10 (S) |
| (c) IC50 and IC25 values of Clarithromycin and 5-Fluorouracil for HCT116 cells cultured as spheroids | ||||
| Drug | IC50 (μM) | IC25 (μM) | ||
| Clarithromycin | >300 | 191.8 ± 21.3 | ||
| 5-FU | 260.8 ± 4.6 | 41.7 ± 8.9 | ||
(a) IC50 values were determined after 24 h of treatment by the Trypan Blue exclusion test, using Origin Software. Data are means ± SEM of four independent experiments, each carried out in triplicate. (b) HCT116 cells were exposed to Irinotecan (CPT-11), 5-Fluorouracil (5-FU), Cisplatin (Cis) or Oxaliplatin (Oxa) alone or in combination with Cla for 24 h as described in ref. 50. IC50 and IC25 vales were determined as in (a). For the determination of the CI the drugs were used at their IC50 and IC25 values. CI values were calculated using Calcusyn software Version 2 (Biosoft). CI > 1, antagonism (A); CI = 1, additivity (Ad); CI < 1, synergy (S). Data are means ± SEM of three independent experiments, each carried out in triplicate. (c) Three-dimensional spheroids were treated for 24 h and IC50 values were determined using Origin Software, after the calculation of the effect of drugs on 3D spheroids volume by Matlab, as reported in Materials and Methods. Data are means ± SEM of five sample for each concentration (n = 2 independent experiments).