Table 1. Compounds that disrupt microfilaments or microtubules selectively target type I and type II cells, respectively.
Act1 | Act2 | Act3 | Act4 | Act5 | Tub1 | Tub2 | Tub3 | Tub4 | Tub5 | |
---|---|---|---|---|---|---|---|---|---|---|
Cell line | ||||||||||
Type I | ||||||||||
IGROV1 | + | + | + | + | + | + | o | o | + | - |
T-47D | nd | nd | nd | - | nd | - | + | - | - | - |
ACHN | + | + | - | + | + | - | - | - | - | - |
CAKI-1 | + | + | + | + | + | - | - | - | - | - |
LOX IMVI | + | + | + | - | + | + | - | + | o | o |
A498 | + | + | + | + | + | - | - | - | - | - |
UO-31 | + | + | + | + | + | - | - | - | - | - |
SF-295 | + | + | + | - | o | - | - | + | - | - |
NCI-H226 | + | + | + | + | + | - | - | - | - | o |
TK-10 | + | + | + | + | + | - | - | - | - | - |
HOP-92 | + | + | + | + | + | - | - | - | - | - |
Type II | ||||||||||
SR | - | - | - | - | + | + | - | + | + | + |
CEM | - | - | + | - | - | + | + | + | + | + |
HCT-15 | - | - | - | - | - | - | - | + | - | + |
NCI-H460 | - | - | - | - | - | + | + | + | + | + |
KM12 | - | - | - | - | - | + | + | + | + | - |
HCT-116 | - | - | - | - | - | + | + | + | + | + |
UACC-62 | - | - | - | - | - | + | o | + | + | + |
HCC 2998 | - | - | + | - | - | + | + | + | + | - |
BT-549 | nd | nd | nd | o | nd | + | + | + | + | + |
NCI-H322M | - | - | - | - | - | + | nd | + | + | - |
RPMI 8226 | - | - | o | - | - | + | + | + | + | + |
PCC | 0.89 | 0.85 | 0.82 | 0.80 | 0.80 | -0.69 | -0.67 | -0.67 | -0.63 | -0.62 |
P (× 10-5) | 0.011 | 0.18 | 1.0 | 0.89 | 3.0 | 82 | 180 | 71 | 310 | 230 |
M conc., μM | 2.42 | 4.71 | 22.64 | 6.19 | 1.13 | 0.107 | 3.85 | 0.07 | 0.57 | 2.81 |
Δ conc., logs | 1.4 | 2.4 | 1.4 | 2.6 | 3.4 | 2.0 | 2.3 | 3.7 | 2.5 | 2.0 |
The information on CD95 cell type of the NCI60 cell lines (Fig. 3A) was used in a compare analysis against the NCI anticancer drug-screen database of >42,000 compounds to identify compounds with patterns of growth inhibition that correlated with either type I or type II cells. Results for five of the actin-binding compounds (Act 1-5) that came up in the search with total growth inhibition as endpoint and results for five of the tubulin-binding compounds (Tub 1-5) that came up in the search with 50% growth inhibition as endpoint are shown. Cell lines that were less sensitive than the mean (across all 22 cell lines) are denoted by a minus (-), and cell lines that were more sensitive than the mean are designated by a plus (+). Cell lines not differing from the mean are indicated by an o. nd, not determined. Act1, NSC 112167, cucurbitacin I; Act2, NSC 94743, cucurbitacin A; Act3, NSC 112166, cucurbitacin K; Act4, NSC 681481, jasplakinolide analog; Act5, NSC 606195, dolastatin 11; Tub1, NSC 666608, Taxol analog; Tub2, NSC 658831, Taxol analog; Tub3, NSC 650773, combretastatin analog; Tub4, NSC 666606, Taxol analog; Tub5, NSC 659853, 2-methoxyestradiol. P values (two-tailed) were not corrected for numbers of compounds in the database. M conc., mean of effective concentration; Δ conc., range in concentration between the least and most sensitive cell line. Complete 60-cell-line data for these compounds can be found at http://dtp.nci.nih.gov.