Table 2 Indole alkaloids targeting p53, NF-κB, PI3K/Akt/mTOR, MAPKs, and other apoptotic pathways in cancer
Compound | Structure | Source | Target | Mechanism in RCD | Cancer cell line | Tumor type | Refs. |
|---|---|---|---|---|---|---|---|
Flavopereirine |
| Geissospermum vellosii | p53, p21↑ | Induce apoptosis | SW480 (IC50 = 15.33 μM); SW620 (IC50 = 10.52 μM); DLD1 (IC50 = 10.76 μM); HCT116 (IC50 = 8.15 μM); HT29 (IC50 = 9.58 μM) | Colorectal cancer | [111] |
Chaetoglobosin K |
| Diplodia macrospora | p53↑ | Induce apoptosis | OVCAR-3 (IC50 = 2.2 μM); A2780/CP70 (IC50 = 1.7 μM); IOSE-364 (IC50 = 11.1 μM) | Ovarian cancer | [112] |
Khasuanine A |
| Melodinuskhasianus | p53↑ Bcl-2↓ | Induce apoptosis | PC3 (IC50 = 0.74 ± 0.03 μM) | Renal carcinoma | [113] |
(Z)-6-Chloro-3-(6,-dimethoxy-1,4-dihydroindeno[1,2-c]pyrazol-3yl))methylene) indolin-2-one |
| - | p53, p21, Bax↑ | Induce apoptosis | HeLa (IC50 = 1.33 μM); A549 (IC50 = 2.44 μM); HEK-293 (IC50 = 2.97 μM); MDA-MB-231 (IC50 = 2.08 μM) | Cervical cancer; lung cancer; breast cancer | [114] |
Melosuavine I |
| Melodinus suaveolens | p53↑ Bcl-2↓ | Induce apoptosis | BT549 (IC50 = 0.89 ± 0.03 μM) | Breast cancer | [115] |
Evodiamine |
| Evodia rutaecarpa | p53, Bax/Bcl-2↑ | Induce apoptosis | HCT-116 | Colorectal cancer | [116] |
|  |  | p53, Bax↑ Bcl-2, NOD1↓ | Induce apoptosis | HepG2, SMMC-7721 (IC50 ≈ 1 μM) | Hepatocellular cancer | [117] | |
Cryptolepine |
| Cryptolepis sanguinolenta | p53↑ | Induce apoptosis | SCC-13; A431 (IC50 = 2.5–5.0 μM) | Non-melanoma skin cancer | [118] |
Fumigaclavine C |
| Aspergillus fumigatus | NF-κB↓ Bax, Bad↑ Bcl-2, Bcl-xL↓ | Induce apoptosis | MCF-7 (IC50 = 40–50 μM) | Breast cancer | [121] |
Vinblastine |
| Catharanthus roseus | NF-κB↓ | Induce apoptosis | NB4 cell | Human acute promyelocytic leukemia | [124] |
Hapalindole H |
| Fischerella muscicola | NF-ĸB↓ | Induce apoptosis | PC-3 (EC50 = 20 nM) | Prostate cancer | [125] |
11-Methoxytabersonine |
| Melodinus cochinchinensis | PI3K/Akt/mTOR↓ | Induce apoptosis | MOLT-4 (IC50 = 0.71 ± 0.08 μM); HL-60 (IC50 = 1.10 ± 0.07 μM) | T cell acute lymphoblastic leukemia | [128] |
Staurosporine |
| Streptomyces staurosporeus | PI3K/Akt↓ | Induce apoptosis | HepG2 | Hepatocellular carcinoma | [129] |
Brucine |
| Strychnos nux vomica L | PI3K/Akt/mTOR↓ | Induce apoptosis | ME-180 (IC50 = 10–20 μM) | Cervical cancer | [130] |
Meisoindigo |
| Indirubin derivative | PI3K/Akt↓ | Induce apoptosis | U87 (IC50 = 20 μM) | Glioblastoma | [132] |
1-(4-Methoxystyryl)-2-benzyl-9-(3-phenylpropyl)-β-carbolinium bromide |
| Harmine derivative | PI3K/Akt↓ | Induce apoptosis | BGC-823 (IC50 = 0.46 μM); A375 (IC50 = 0.68 μM); KB (IC50 = 0.93 μM) | Colorectal cancer; gastric cancer; malignant melanoma | [133] |
Harmalacidine |
| Peganum harmala | PTKs-Ras/Raf/ERK↓ | Induce apoptosis | U937 (IC50 = 3.1 ± 0.2 μM) | Leukemia | [136] |
Dehydrocrenatidine |
| Picrasma quassioides | ERK1/2, JNK1/2↑ | Induce apoptosis | SAS, SCC-9 | Oral squamous cell carcinoma | [137] |
|  |  | ERK1/2↑ JNK1/2↓ | Induce apoptosis | NPC-039, NPC-BM, RPMI-2650 | Nasopharyngeal carcinoma | [138] | |
3α-Acetonyltabersonine |
| Melodinus suaveolens | MAPK↑ | Induce apoptosis | U87 (IC50 = 1.7 μM); T98G (IC50 = 4.3 μM) | Glioblastoma | [140] |
Flavopereirine |
| Geissospermum vellosii | ERK, p38 MAPK↑ AKT↓ | Induce apoptosis | MDA-MB-231 (IC50 = 5.96 μM); MCF-7 (IC50 = 12.43 μM) | Breast cancer | [141] |
Jerantinine B |
| Tabernaemontana corymbosa | c-Jun/JNK↑ | Induce apoptosis | MV4–11 (IC50 = 0.3 μM); HL-60 (IC50 = 0.4 μM); KG1a (IC50 = 0.8 μM) | Acute myeloid leukemia | [142] |
Sclerotiamides C |
| Aspergillus sclerotiorum | JNK, ERK, and p38↑ | Induce apoptosis | HeLa (IC50 = 1.7 ± 0.1 μM) | Cervical cancer | [143] |
L20 |
| Calothrixin B derivative | p38 MAPK↑ | Induce apoptosis | HEL (IC50 = 1.10 ± 0.05 μM); K562 (IC50 = 5.46 ± 3.09 μM); KG-1a (IC50 = 1.82 ± 1.08 μM) | Erythroleukemia | [144] |
Brucine and strychnine |
| Strychnos nux vomica L | Wnt/β-catenin↓ | Induce apoptosis | DLD1, SW480, and Lovo | Colon cancer | [146] |
Nauclefine |
| Nauclea subdita | PDE3A-SLFN12↑ | Induce apoptosis | HeLa (IC50 < 10 nM) | Cervical cancer | [149] |
SOID-8 |
| Spirooxindole derivative | JAK/STAT3↓ | Induce apoptosis | A2058 (IC50 = 3.7 μM); A375 (IC50 = 5.3 μM) | Melanoma | [150] |
3,10-Dibromofascaplysin |
| Fascaplysinopsis reticulata | E2F1↑ | Induce apoptosis | K562 (IC50 = 318.2 nM); THP-1 (IC50 = 329.6 nM); MV4;11 (IC50 = 233.8 nM); U937 (IC50 = 318.1 nM); | Myeloid Leukemia | [152] |
3-Chloro-5‴-fluorofradcarbazole A |
| Staurosporine derivative | FLT-3, c-kit↓ | Induce apoptosis | MV4-11 (IC50 = 0.32 ± 0.03 μM) | Acute myeloid leukemia | [155] |
Dregamine 5-bromo-pyridin-2-ylhydrazone |
| Monoterpene indole alkaloid derivative | BRCA1-BARD1↓ PUMA, PARP↑ | Induce apoptosis | SKOV-3 (IC50 = 8.9 ± 2.5 μM); MDA-MB-468 (IC50 = 4.3 ± 1.2 μM); IGROV-1 (IC50 = 4.6 ± 1.5 μM) | Triple-negative breast cancer; ovarian cancer | [158] |
