Table 1.
Published studies since 2002 in Pubmed, reporting an anti-tumor effect (anti-proliferative and/or apoptotic effect) of PRIMA-1 or APR-246 in malignant disease, using established human cell lines, primary cultures or xenografts.
| Reference | Molecule | Cancer Type | Reported IC50 (µmol/L) |
Established Cell Line | Primary Culture (n) | Xenograft | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Wild-Type 53 | Mutant p53 | p53 Null | p53 KD | Wild-Type p53 | Mutant p53 | p53 Null | |||||
| [7] | PRIMA-1 | Colorectal, lung, ovary, burkitt lymphoma, osteosarcoma | (0.75–65) | HCT116, HDF, IARC-171 EW36, Seraphin, KH39, Caki1 |
A461, SW480, Ramos, BL60, CW678, BL41, TK-10, KRC/Y+ (Saos-2-273, H1299-175, SKOV-175, SKOV-273, SKOV-175-22/23) a |
H1299, Saos-2, SKOV |
HCT116 | Yes | |||
| [10] | PRIMA-1 | Lung (non-small cell) | H460 | H23 | H1299 | ||||||
| [11] | PRIMA-1 | B cell chronic leukemia | 9 b | 5 c | |||||||
| [12] | PRIMA-1 | breast | (51–122) | MCF7 | MDA-MB-231, GI-101A | ||||||
| [8] | PRIMA-1 and APR-246 | Colorectal, lung, osteosarcoma | PRIMA-1: (14–24) APR-246: (9–19) |
HCT116 | SW480+ (Saos-2-273, H1299-175) a |
H1299, Saos-2 |
HCT116 | Yes | |||
| [13] | PRIMA-1 | Acute myeloid leukemia | 52 b | 8 c | |||||||
| [14] | PRIMA-1 | Breast | MCF7 | DA-MB-231 | |||||||
| [15] | PRIMA-1 | Breast | MCF7 | MDA-MB-231, GI-101A | MDA-MB-231, GI-101A | ||||||
| [16] | PRIMA-1 | Colorectal, lung, breast, osteosarcoma | MCF7, U205 | SW480 + (H1299-175) a |
H1299 | ||||||
| [17] | PRIMA-1 | Lung (non-small cell) | (60–175) * | A549 | LX1, SKMes | ||||||
| [18] | APR-246 | Prostate | 22RV1 | DU145 | PC3 | ||||||
| [19] | PRIMA-1 | Hepato-cellular carcinoma | Mahlavu, PLC5/PRF/5 + (Hep3B-249, Hep3B-248) a |
Hep3B | PLC5/PRF/5 | Yes | |||||
| [20] | APR-246 | Colorectal, lung, osteosarcoma, lymphoma | MQ: (14.8;20.6) | HCT116 + (H1299, BL41) d |
SBL41 + (Saos-2-273, H1299-175) a |
H1299, Saos-2 |
HCT116 | ||||
| [21] | APR-246 | Colorectal, lung, breast, lymphocyte | MCF7 | SW480 + (H1299-175) a |
H1299 | ||||||
| [22] | APR-246 | Colon, lung, osteosarcoma | HCT116 + (Saos-2) d |
SW480 + (Saos-2-273, H1299-175, HCT-116-248) a |
H1299, Saos-2 |
HCT116 | |||||
| [23] | PRIMA-1 | Breast | MDA-MB-231 | MDA-MB-231 | |||||||
| [24] | APR-246 | Colorectal, lung, osteosarcoma | (17–27) * | H1299, Saos-2-TA-p63γ, H1299-TA-p73α, H1299-TA-p73β, H1299-TA-p63γ |
HCT116 | ||||||
| [25] | PRIMA-1 | Lung | A549 | H211, H1155 | H1299 | ||||||
| [26] | PRIMA-1 | Head and neck | JHU-028 | UMSCC-22a, JHU-029, Fadu | |||||||
| [27] | APR-246 | Lung (small cell) | (CCD32Lu) e | DMS456, DMS406, DMS273, DMS153, DMS114, DMS92, DMS79, DMS53, NCIH69, MAR24h, MAR86MI, GLC28, GLC26, GLC19, GLC16, GLC14, GLC3, GLC2 + (MDA-MB-231) f |
H1299 | DMS273, DMS53, GLC16 | Yes | ||||
| [28] | PRIMA-1 | Breast | BT-474, HCC-1428 | Yes | |||||||
| [29] | APR-246 | Melanoma | AA, FM88 | C8161 + (M21) g |
Yes | ||||||
| [30] | APR-246 | Acute myeloid leukemia | Mean = 5 | KBM3 | 25 | 7 | |||||
| [31] | PRIMA-1 | Thyroid | (10–75) * | TPC-1 | BC-PAP, Hth-74, FTC-133, C-643, 8305-C, FF-1 | SW1736 | Hth-74 | Data not found | |||
| [32] | PRIMA-1 | Breast | MCF7 | SKBR3 + (MCF7) a |
|||||||
| [33] | PRIMA-1 | Breast | MCF7, MRC5 + (HCT116) j |
MDA-MB-231, DLD-1 | T1 + (HCT116) j |
||||||
| [34] | APR-246 | Lung, osteosarcoma, burkitt lymphoma | (BL41) d | BL41 + (Saos-2-273, H1299-175) a |
H1299, Saos-2 |
||||||
| [35] | PRIMA-1 | Ovary | A2781cp | A2781cp | |||||||
| [36] | APR-246 | Myeloma | Cell line: (5–20) * Primary culture: (4–30) * |
MM1S, H929 | LP1, U266, 8266 | 8266R5 | MM1S, U266 | 6 | 3 c | Yes | |
| [32] | PRIMA-1 | Pancreas | (65–70) | Capan-2 | PANC-1, BxPC-3 | PANC-1 | |||||
| [37] | APR-246 | Myeloma | (3–200) | XG6, XG3, XG7, BCN, NAN9, H929, MDN, MM1S, AMO | NAN10, SKMM2, U266, XG1, XG11, XG5, 8226, JIM3, LP1, OPM2, XG2 + (NAN3, KMN1) h |
JJN3, KMS11, NAN1, L363 | XG6, H929, XG5 |
16 b | 7 c | Yes | |
| [38] | PRIMA-1 | Thyroid | TPC-1, K1, IHH4 | FTC-133, WRO, 8505C, C-643, BC-PAP | |||||||
| [39] | PRIMA-1 | Thyroid | (28.7–128.5) | K1, IHH4 | C-643, BC-PAP | ||||||
| [40] | APR-246 | Ovary | (11–37) | A2780, A2780cis, A2780adr | OVCAR-3, A2780-CP20, IGROV-1/CDDP + (H1770, H1975, H596, H378) i |
(H1417) i | 1 | 4 | Yes | ||
| [41] | APR-246 | Sarcoma | (7.9–26.1) | IB139 + (HCT116) j |
IB130, IB134, IB138 + (HT-29) j |
IB136, IB117 | |||||
| [42] | APR-246 | Colorectal | (7–58.6) | HCT116, RKO, LOVO | DLD-1, SW480, SW620, Colo320, Caco2, HT29 | HCT116 | Yes | ||||
| [43] | APR-246 | Waldenström | (10–30) | BCWM-1 | MWCL-1 | 2 | |||||
| [44] | PRIMA-1 | Bladder | RT4 | T24, T24-X | |||||||
| [45] | PRIMA-1 | Breast | MCF-10A | T47D, MDA-MB-468 | |||||||
| [46] | PRIMA-1 | Lung (non-small cell) | A549 | NSCLL-N6 | |||||||
| [47] | PRIMA-1 | Thyroid | WRO | FTC-133 | |||||||
| [48] | APR-246 | Oesophageal | (10–100) * | (NES) k, l | FLO-1, Eso26, OE19, OANC1, JH-EsoAd1, SKGT4, OE33, OACM5.1 + (H1299) a,i |
OACP4C, TE7 m + (H1299) i |
OACM5.1, OANC1, FLO-1, OE19, JH-EsoAd | Yes | |||
| [49] | PRIMA-1 | Prostate | LNCap + (PC3) d |
DU145 + (PC3) a |
PC3 | Yes | |||||
| [50] | APR-246 | Lung (non-small cell) | (9.56–29.35) | A549 | 1975, H2228, H596 | ||||||
| [51] | APR-246 | Ovary | (5.2–56) | 1 | 9 n | ||||||
| [52] | APR-246 | Ovary | (2.6–20.1) | NOS2, TOV21G, A2780 | NOS3, OVCAR-3, CAOV-3, OV-90, ES-2 | SKOV-3 | |||||
| [53] | APR-246 | Acute myeloid leukemia | (HCT116) j | KBM3 + (HCT116) a,j |
(HCT116) j | 5 | |||||
| [54] | PRIMA-1 and APR-246 | Myeloma | PRIMA-1: (16.3–88.9) APR-246: (2–24.5) |
H929 + (XG6, KMS18) h |
U266, 8226, KMS28 | KMS11 + (JJN3) m |
H929 | ||||
| [55] | APR-246 | Myelome | MM1S, H929 | U266, 8226, LP1 | 5 | Yes | |||||
| [56] | APR-246 | Colorectal | HCT 116, LOVO | SW480, DLD-1, HT29 | HCT116 | SW480, DLD-1 | Yes | ||||
| [57] | APR-246 | Ewing sarcoma | TC252 | STA-ET-7.2, RDES, IARC-EW2, RM82, SK-ES1, STA-ET-2.2 + (MDA-MB-468) f |
A673, SK-N-MC | STA-ET-7.2 | (+3) o | ||||
| [58] | APR-246 | Melanoma | MM070, MM034, MM050,MM133, MM032, MM043, MM074-R, MM029, MM074, MM054 |
Sk-MEL-28, MM164 | Yes | ||||||
| [59] | PRIMA-1 | Melanoma | MelJuso, C8161 + (A549) i |
||||||||
| [60] | APR-246 | Glioblastoma | (60–100) | U87MG, U87/EV, U87/MGMT | T98/EV, T98/shRNA, U138, LN-18, A172 | ||||||
| [61] | PRIMA-1 and APR-246 | Breast | PRIMA-1: (1.4–15.1) APR-246: (0.9–31.1) |
UACC812, Hs878T(i8), ZR-75-1,MCF7,BT474 + (MCF12A, MCF10A) k |
Hs878T(i8)2, HCC70, Hs578T, CAL-85-1, HCC1143, BT474, HCC1937, HDQ-P1, BT20, JimT1, Cama1, T47D, BT549,MDA-MB-468, MDA-MB-453 | ||||||
| [62] | APR-246 | Oesophageal | (NES) k,l | FLO-1, Eso26, OE19, OANC1, JH-EsoAd1, SKGT4, OE33, OACM5.1 + (H1299) a,i |
OACP4C, TE7 m + (H1299) i |
OACM5.1, OANC1, FLO-1, OE19, JH-EsoAd | Yes | ||||
| [63] | PRIMA-1 | Acute promyelocytic leukemia | NB4 | ||||||||
| [64] | APR-246 | Melanoma | MM161, MM057, MM165, MM052, MM167 | MM125 | |||||||
* IC50 estimated on graphs; a Cell lines genetically modified to introduce a mutant-p53 gene; b Without hemizygous p53-deletion or with less than 50% of hemizygous 53-deletion; c With hemizygous p53-deletion; d Cell lines genetically modified to introduce a wild-type p53 gene; e Normal fibroblast cell line; f Breast cancer cell line; g Cell line with mutant-p53 that it behaves as a wild-type-p53; h Cell line presenting a mixed status: wild-type/mutant p53; i Lung cell line; j Colon cell line; k Immortalized cell lines; l Normal oesohageal cell line; m Mutated cell lines classified as p53null because no protein expression was detected; n Cell lines with p53 missense mutations (n = 7) or nonsense mutations (n = 2); o The three cell lines were from the same patient, with several origin (primary tumor or metastasis); p Gastric cell line.