Table 1 Small-molecule compounds targeting apoptosis in TNBC
Name in the literature and chemical structure | Target | Mechanism in RCD | Biological activity | TNBC subtype | References |
|---|---|---|---|---|---|
C20E
| TNFR1/ASK1/JNK↑ | Induce apoptosis | MDA-MB-231 (IC50 = 40 μM) | MSL | [31] |
CPT211
| Fas/FADD/caspase-8↑ | Induce apoptosis | MDA-MB-231 (IC50 = 478.4 nM) | MSL | [32] |
Pterostilbene (PTER)
| DR4/DR5↑ Cellular FLICE-inhibitory protein (c-FLIP)↓ Bcl-xl↓ Bcl-2↓ | Induce apoptosis | MDA-MB-468 (IC50 = 30 − 40 μM); BT-20 (IC50 = 50 − 60 μM) | BL1 | [34] |
Doscadenamide A
| TRAIL/DR↑ | Induce apoptosis | MDA-MB-231 | MSL | [35] |
MnIII complex
| TNF-α/TNFR↑ Bcl-2↓ Bax↑ caspase-8,9↑ | Induce apoptosis | MDA-MB-231 (IC50 = 2.28 ± 0.38 μM) | MSL | [37] |
CYD-6–28
| DR5↑ | Induce apoptosis | HCC1806, HCC1937 (IC50 = 2 − 3 μM) | BL2, BL1 | [38] |
MEDI3039 | DR5↑ | Induce apoptosis | MDA-MB-231 (IC50 = 4.71 μM) | MSL | [39] |
Spirooxindole 6e
| Bcl-2↓ Bax↑ caspase-3↑ | Induce apoptosis | MDA-MB-231 (IC50 = 6.40 μM) | MSL | [46] |
Compound 10Â g
| Bcl-2↓ Bax↑ caspase-3,9↑ | Induce apoptosis | MDA-MB-231 (IC50 = 12.0 ± 0.13 μM) | MSL | [47] |
Sophoraflavanone G (SG)
| Bcl-2↓ Bcl-xl↓ ERK/AKT↓ Bax↑ caspase-3↑ Cyt-c↑ | Induce apoptosis | MDA-MB-231 (IC50 = 29.7 ± 5.2 μM) | MSL | [48] |
Ilamycin E
| CHOP↑ Bcl-2↓ | Induce apoptosis | HCC1806 (IC50 = 47.50 μM), HCC1937 (IC50 = 14.24 μM), MDA-MB-468 (IC50 = 24.56 μM), MDA-MB-231 (IC50 = 33.72 μM) | BL2, BL1, MSL | [49] |
Gallic acid (GA)
| Bax↑ caspase-3↑ Bcl-2↓ | Induce apoptosis | MDA-MB-231 (IC50 = 50 μM) | MSL | [50] |
Curcumin (Cur)
| Bax↑ caspase-3↑ Bcl-2↓ | Induce apoptosis | MDA-MB-231 (IC50 = 30 μM) | MSL | [50] |
KYZ3
| Bcl-2↓ Bax↑ | Induce apoptosis | MDA-MB-231 (IC50 = 0.68 μM), MDA-MB-468 (IC50 = 0.86 μM) | MSL, BL1 | [51] |
Compound 7d
| Bax↑ Bim↑ Cyt-c↑ | Induce apoptosis | MDA-MB-231 (IC50 = 0.25 μM), SUM159 (IC50 = 0.20 μM), 4T1 (IC50 = 0.22 μM) | MSL | [52] |
CYD-4–61
| Bax↑ Cyt-c↑ | Induce apoptosis | MDA-MB-231 (IC50 = 0.07 μM), MDA-MB-468 (IC50 = 1.61 μM) | MSL, BL1 | [53] |
Arctigenin (ATG) (+ DOX)
| Bcl-2↓ Bcl-xl↓ Bax↑ | Induce apoptosis | MDA-MB-231 (ATG: IC50 = 10 − 25 μM; DOX: IC50 = 0.2 μM) | MSL | [58] |
Coralyne (+ PTX)
| Bcl-2↓ Bax↑ | Induce apoptosis | MDA-MB-231 (Coralyne: IC50 = 21.9 ± 1.36 μM; PTX: IC50 = 0.018 ± 1.83 μM) | MSL | [59] |
FZU-0038–056
| Bcl-2↓ Mcl-1↓ XIAP↓ | Induce apoptosis | HCC1806, HCC1937 (IC50 = 3 − 6 μM) | BL2, BL1 | [60] |
Oleandrin
| Bcl-2↓ Bax↑ Bim↑ | Induce apoptosis | MB-MDA-231 (IC50 = 24.62 nM) | MSL | [62] |
(-)-Sativan (SA)
| Bcl-2↓ Bax↑ Programmed cell death ligand 1 (PD-L1) ↓ | Induce apoptosis | MDA-MB-231 (IC50 = 38.39 μM) BT549 (IC50 = 27.65 μM) | MSL, M | [63] |
Cardamonin (CD)
| Bcl-2↓ Bax↑ Cyt-c↑ caspase-3↑ PARP↑ | Induce apoptosis | MDA-MB-231 (IC50 = 10 − 20 μM), BT-549 (IC50 = 0 − 10 μM) | MSL, M | [64] |
Artesunate
| Bcl-2↓Heat shock protein 70 (HSP70) ↓ caspase-9↑ | Induce apoptosis | 4T1 (IC50 = 52.41 μM) |  | [65] |
Tetramethoxychalcone (TMC)
| Bcl-2↓ Bax↑ | Induce apoptosis | MDA-MB-231 (IC50 = 8.696 μM), BT549 (IC50 = 14.28 μM) | MSL, M | [66] |
Trifluridine (TFT)
| Bcl-2↓ Bax↑ caspase-7↑ | Induce apoptosis | MDA-MB-231, BT-549, Hs578T (IC50 = 10 − 20 μM) | MSL, M | [67] |
CCT020312
| Bcl-2↓ Bax↑ PARP↑ | Induce apoptosis | MDA-MB-453 (IC50 = 5 − 6 μM), CAL-148 (IC50 = 8 − 10 μM) | MSL, LAR | [68] |
CH5126766
| Bcl-2↓ Bcl-xl↓ | Induce apoptosis | MDA-MB-231 (IC50 = 3 − 10 μM) | MSL | [69] |
Physciosporin (PHY)
| Bax↑ Bcl-xl↓ | Induce apoptosis | MDA-MB-231 (IC50 = 27.3 μM) | MSL | [70] |
CPSI-1306
| ROS↑ Cyt-c↑ | Induce apoptosis | MDA-MB-468 (IC50 = 0.84 μM); MDA-MB-231 (IC50 = 1.16 μM) | BL1, MSL | [73] |
Berberine (BBR)
| Cyt-c↑ caspase-9↑ | Induce apoptosis | BT549 (IC50 = 16.575 ± 1.219 μM); MDA-MB-231 (IC50 = 18.525 ± 6.139 μM) | M, MSL | [75] |
Budlein A methylacrylate (BAM)
| NF-κB↓ | Induce apoptosis | MDA-MB-231 (IC50 = 1.55 μM); MDA-MB-453 (IC50 = 1.75 μM); MDA-MB-436 (IC50 = 4.53 μM) | MSL, LAR | [79] |
Icariin
| SIRT6↑ NF-ΚB↓ | Induce apoptosis | MDA-MB-231 (IC50 = 10 − 15 μM); MDA-MB-453 (IC50 = 5 − 10 μM) | MSL, LAR | [80] |
Crambescidin 800 (C800)
| Akt↓ NF-κB↓ MAPK↓ | Induce apoptosis | SUM159PT (IC50 = 3.42 ± 0.07 μM); MDA-MB-231 (IC50 = 5.00 ± 0.57 μM); SUM149PT (IC50 = 6.02 ± 0.14 μM) | MSL, BL2 | [81] |
ACT001
| NF-κB↓ | Induce apoptosis | 4T1 (IC50 = 43.2 μM) |  | [82] |
Cedrelone acetate
| NF-κB↓ EGFR↓ Akt↓ | Induce apoptosis | MDA-MB-231 (IC50 = 1.28 ± 0.04 μM) | MSL | [83] |
Ginsenoside panaxatriol (GPT)
| NF-κB↓ ERK↓ | Induce apoptosis | MB231-PR (IC50 = 21.39 μM) | MSL | [85] |
Rg3
| NF-κB↓ | Induce apoptosis | MDA-MB-231, MDA-MB-453, BT-549 (IC50 = 20 − 25 μM) | MSL, LAR, M | [86] |
Oprozomib
| NF-κB↓ | Induce apoptosis | MDA-MB-231 (IC50 = 0.079 μM); BT-549 (IC50 = 0.05 μM) | MSL, M | [87] |
Carfilzomib (CARF)
| NF-κB↓ | Induce apoptosis | MDA-MB-231 (IC50 = 0 − 50 nM); MDA-MB-468 (IC50 = 50 − 100 nM) | MSL, BL1 | [88] |
DCC-2036
| PI3K/Akt-NF-κB↓ | Induce apoptosis | MDA-MB-231 (IC50 = 3.3 μM); HS-578 T (IC50 = 3.7 μM) | MSL | [89] |
Aurantoside C (C828)
| Akt/mammalian target of rapamycin (mTOR) ↓ NF-κB↓ P38 MAPK↑ Stress-activated protein kinase (SAPK)/JNK↑ | Induce apoptosis | SUM159PT (IC50 = 0.56 ± 0.01 μM); MDA-MB-231 (IC50 = 0.61 ± 0.01 μM); SUM149PT (IC50 = 0.81 ± 0.02 μM) | MSL, BL2 | [91] |
KHF16
| NF-κB↓ | Induce apoptosis | MDA-MB-231 (IC50 = 6.8 μM); MDA-MB-468 (IC50 = 9.2 μM); SW527 (IC50 = 5 − 6 μM) | MSL, BL1 | [92] |
Noscapine
| NF-κB↓ | Induce apoptosis | MDA-MB-231 (IC50 = 20 μM) | MSL | [93] |
SC-60
| SHP-1/STAT3↓ | Induce apoptosis | MDA-MB-231 (IC50 = 0.9 − 1.1 μM); MDA-MB-468 (IC50 = 1.8 − 2.0 μM); HCC1937 (IC50 = 3.9 − 4.1 μM) | MSL, BL1 | [99] |
SC-43
| SHP-1/STAT3↓ | Induce apoptosis | MDA-MB-231 (IC50 = 1.18 μM); MDA-MB-468 (IC50 = 1.3 μM); HCC1937 (IC50 = 1.72 μM) | MSL, BL1 | [100] |
SG-1721
| STAT3↓ | Induce apoptosis | MDA-MB-468 (IC50 = 6.90 μM) | BL1 | [101] |
Compound 15d
| LIFR-JAK-STAT3↓ | Induce apoptosis | MDA-MD-231 (IC50 = 3.83 ± 0.27 μM) | MSL | [102] |
Ilamycin C
| IL-6/STAT3↓ | Induce apoptosis | MDA-MD-231 (IC50 = 7.26 μM) ; BT549 (IC50 = 6.91 μM) | MSL, M | [103] |
Osthole
| STAT3↓ | Induce apoptosis | MDA-MD-231 (IC50 = 90.66 μM); BT549 (IC50 = 77.19 μM); MDA-MD-468 (IC50 = 70.65 μM) | MSL, M, BL1 | [104] |
Bt354
| STAT3↓ | Induce apoptosis | MDA-MB-435 (IC50 = 6.5 μM); MDA-MB-231 (IC50 = 7.2 μM) | MSL, | [105] |
Primaquine
| EGFR/STAT3↓ | Induce apoptosis | MDA-MB-231 (IC50 = 81.2 μM) | MSL | [106] |
Eupalinolide J (EJ)
| STAT3↓ | Induce apoptosis | MDA-MB-231 (IC50 = 3.74 ± 0.58 μM); MDA-MB-468 (IC50 = 4.30 ± 0.39 μM) | MSL, BL1 | [107] |
LLY17
| IL-6/STAT3↓ | Induce apoptosis | MDA-MB-468, MDA-MB-231, SUM159, BT-549 | MSL, BL1, M | [108] |
Pulvomycin
| STAT3↓ | Induce apoptosis | MDA-MB-231 (IC50 = 2 − 3 μM) | MSL | [109] |
APR-246
| p53↑ | Induce apoptosis | MDA-MD-468, BT549 (IC50 = 2 − 4 μM); BT20 (IC50 = 4 − 6 μM) | BL1, M | |
CX-5461
| p53↑ | Induce apoptosis | Hs578T (IC50 = 9.2 μM); BT549 (IC50 = 1.7 μM); MDA-MD-231 (IC50 = 1.6 μM); SUM159PT (IC50 = 2.0 μM) | M, MSL |  |
COTI-2
| p53↑ | Induce apoptosis | Hs578T (IC50 = 21.3 ± 5.4 nM); MDA-MD-468 (IC50 = 71.1 ± 15.1 nM); MDA-MD-231 (IC50 = 59.1 ± 4.9 nM); BT549 (IC50 = 2.5 ± 0.6 nM) | BL1, MSL, M | [118] |
PK11007
| p53↑ | Induce apoptosis | MDA-MD-468 (IC50 = 2.8 ± 0.3 μM); HCC1937 (IC50 = 6.8 ± 3.2 μM); HCC1143 (IC50 = 2.3 ± 0.3 μM); BT549 (IC50 = 3.4 ± 0.6 μM); Hs578T (IC50 = 5.3 ± 0.7 μM) | BL1, M, MSL | [119] |
Compound 5i
| p53↑ MDM2↓ | Induce apoptosis | MDA-MB-231 (IC50 = 3.5 ± 1.0 μM) | MSL | [120] |
Ruthenium (II)/allopurinol complex
| p53↑ | Induce apoptosis | MDA-MB-231 (IC50 = 9.1 ± 0.9 μM) | MSL | [121] |
Resveratrol (RSV)
| p53↑ Polymerase (DNA) delta 1 (POLD1) ↓ | Induce apoptosis | MDA-MB-231 (IC50 = 50 μM) | MSL | [122] |
Ziyuglycoside I
| p53↑ p21WAF1↑ | Induce apoptosis | MDA-MB-231 (IC50 = 13.96 μM) | MSL | [123] |
α-Conidendrin
| p53↑ p21↑ | Induce apoptosis | MDA-MB-231 (IC50 = 3.5 ± 1.0 μM) | MSL | [124] |
I-7ab
| p53↑ | Induce apoptosis | MDA-MB-231 (IC50 = 35.48 μM); BT-20 (IC50 = 38.02 μM) | MSL | [125] |
Ciprofloxacin
| p53↑ | Induce apoptosis | MDA-MB-231 (IC50 = 0.03 μM) | MSL | [126] |
