Table 1 Indole alkaloids targeting death receptors and their ligands, Bcl-2 family and Cyt-C, in cancer
Compound | Structure | Source | Target | Mechanism in RCD | Cancer cell line | Tumor type | Refs. |
|---|---|---|---|---|---|---|---|
Harmaline |
| Peganum harmala | Fas/FasL↑ caspase-8/-3↑ | Induce apoptosis | SGC-7901 (IC50 = 4.08 ± 0.89 μM) | Gastric cancer | [56] |
Scholarisines Q and R |
| Alstonia scholaris | TNF-α, caspase-3↑ | Induce apoptosis | GSC-3#, GSC-12#, GSC-18# (IC50 = 15–25 μM) | Glioblastoma multiform | [57] |
N-(p-coumaroyl) serotonin |
| Centaurea vlachorum | Caspase-8↑ | Induce apoptosis | U251MG (IC50 = 77 μM); T98G (IC50 = 68 μM) | Glioblastoma | [59] |
Harmine |
| Peganum harmala | COX-2, Bcl-2, MMP-2↓ Bax↑ | Induce apoptosis | BGC-823 (IC50 = 3.63 ± 0.54 μM); SGC-7901 (IC50 = 2.92 ± 0.34 μM) | Gastric cancer | [65] |
|  |  | TAZ, Bcl-2↓ Bax↑ |  | MDA-MB-231 and MCF-7 | Breast cancer | [66] | |
JKA97 |
| Harmine derivative | Bax, Cyt-C↑ | Induce apoptosis | HCT116 | Colon cancer | [67] |
|  |  | p21↑ |  | MCF-7 (IC50 = 19.0 ± 0.7 μM); MDA-MB-468 (IC50 = 6.6 ± 0.5 μM); MCF-7 p53KD (IC50 = 10.3 ± 2.7 μM) | Breast cancer | [68] | |
Subditine |
| Nauclea subdita | Bcl-2, Bcl-xL↓ Cyt-C, p53↑ | Induce apoptosis | LNCaP (IC50 = 12.24 ± 0.19 μM); PC-3 (IC50 = 13.97 ± 0.32 μM) | Prostate cancer | [69] |
Dehydrocrenatidine |
| Picrasma quassioides | Bax↑ Bcl-2↓ | Induce apoptosis | HepG2 (IC50 = 3.50 ± 0.29 μM); Hep3B (IC50 = 5.87 ± 0.48 μM) | Hepatocellular carcinoma | [70] |
9-Hydroxycanthin-6-one |
| Ailanthus altissima | Caspase-3/8/9↑ | Induce apoptosis | A2780 (IC50 = 10.62 μM), SKOV3 (IC50 = 34.7 μM), and OVCAR-3 (IC50 = 42.13 μM) | Ovarian cancer | [71] |
Evodiamine |
| Evodia rutaecarpa | Cyt-C↑ | Induce apoptosis | A549, H1299, A431 | Lung cancer | [73] |
|  |  | Mcl-1↓ | Induce apoptosis | 253 J (IC50 = 1.90 ± 0.31 μM); T24 (IC50 = 2.14 ± 0.26 μM) | Bladder cancer | [76] | |
Vinorelbine |
| Vinca alkaloid | Bax↑ Bcl-2, Bcl-xL↓ | Induce apoptosis | H1975 (IC50 = 0.008 ± 0.001 μM); HepG2 (IC50 = 0.11 ± 0.01 μM); and HCT116 (IC50 = 0.0149 ± 0.002 μM) | Lung cancer; liver cancer; colorectal cancer | [77] |
Vincamine |
| Vinca minor | Caspase-3, Cyt-C↑ | Induce apoptosis | A549 (IC50 = 309.7 μM) | Lung cancer | [78] |
Gramine |
| Barley and silver maple | Bcl-2↓ Bax, Cyt-C, apaf-1↑ | Induce apoptosis | 7,12-Dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch | Oral squamous cell carcinoma | [82] |
Gramine derivative (16Â h) |
| Gramine derivative | Bax, PARP↑ Bcl-2↓ | Induce apoptosis | MGC803 (IC50 = 3.74 μM) | Gastric cancer | [83] |
Indole-3-carbinol |
| Cruciferous vegetables | ROS, Bax↑ Bcl-2, Bcl-xL↓ | Induce apoptosis | H1299 | Lung cancer | [84] |
Cathachunine |
| Catharanthus roseus | Bcl-2↓ Bax, Cyt-C↑ | Induce apoptosis | HL60 (IC50 = 9.1 ± 0.7 μM); K562 (IC50 = 9.3 ± 1.8 μM) | Leukemia | [85] |
(3′R)-hydroxytaberanelegantine C |
| Tabernaemontana elegans | Bcl-2, XIAP↓ | Induce apoptosis | HCT116 (IC50 = 3.20 μM); SW620 (IC50 = 3.49 μM); HepG2 (IC50 = 3 μM) | Colorectal cancer, colon cancer, liver cancer | [86] |
Cimicifoetones |
| Cimicifuga foetida | Caspase-3/-8/-9↑ Bcl-2, Bcl-xL↓ Bax↑ | Induce apoptosis | HL-60 (IC50 = 1.36 ± 0.09 μM) | Leukemia | [87] |
Staurosporine |
| Streptomyces staurosporeus | Bcl-2, Bad↓ Bax↑ | Induce apoptosis | PaTu 8988t, Panc-1 | Pancreatic cancer | [88] |
2,2-Bis(6-bromo-3-indolyl) ethylamine |
| Didemnum candidum and the New Caledonian sponge Orina | Bcl-2, Bcl-xL↓ Bax↑ | Induce apoptosis | U937 | Leukemia | [89] |
Eusynstyelamide B |
| Didemnum candidum | Cleaved PARP, caspase-3↑ | Induce apoptosis | MDA-MB-231 (IC50 = 5.0 μM) | Breast cancer | [90] |
Chetomin |
| Chaetomium cochliodes | Bcl-2↓ Bax, Cyt-C↑ PI3K/mTOR↓ | Induce apoptosis | MDA-MB-231; MDA-MB-468 | Triple-negative breast cancer | [91] |
Chaetoglobosin A |
| Penicillium aquamarinium | Caspase-3↑ | Induce apoptosis | MEC-1 | Chronic lymphocytic leukemia | [92] |
[11]-chaetoglobosin B |
| Pseudeurotium bakeri P1-1–1 | Bax, Cyt-C, PARP↑ Bcl-2↓ | Induce apoptosis | MCF-7 (IC50 = 6.2 ± 1.1 μM); A427 (IC50 = 4.7 ± 1.0 μM) | Breast cancer; lung cancer | [93] |
Chaetominine |
| Aspergillus fumigatus | ROS, Bax↑ Bcl-2↓ | Induce apoptosis | K562 (IC50 = 33.7 ± 0.2 nM); K562/Adr (IC50 = 47.9 ± 1.1 nM) | Leukemia | [94] |
Reserpine |
| Rauwolfia serpentina | TGF-β↓ Bax, Cyt-C, Apaf-1↑ | Induce apoptosis | DMBA-induced hamster buccal pouch carcinogenesis model | Oral squamous cell carcinoma | [96] |
Brucine |
| Strychnos nux vomica L | Caspase-3, Bax↑ Bcl-2↓ | Induce apoptosis | Rats | Hepatocellular carcinoma | [98] |
Jerantinine B |
| Tabernaemontana corymbosa | Bcl-2, Mcl-1↓ | Induce apoptosis | HCT-116, A549, MCF-7 (GI50 = 0.7–0.9 μM); MIA PaCa-2 (GI50 ≈ 0.25 μM) | Colorectal cancer; gastric cancer; breast cancer; pancreatic cancer | [99] |
Isorhynchophylline |
| Uncaria rhynchophylla | Bcl-2, Bcl-xL↓ | Induce apoptosis | HepG2 (IC50 = 130 μM) | Hepatocellular carcinoma | [100] |
Bufothionine |
| Toad Bufo bufo gargarizans Cantor | Bcl-2↓ Bax↑ | Induce apoptosis | MKN28 and AGS cells | Gastric cancer | [101] |
CAA45 |
| Calothrixin A derivative | Bcl-2↓ Bax, Bad, Cyt-C↑ | Induce apoptosis | A549 (IC50 = 110 nM); NCI-H1650 (IC50 = 230 nM) | Lung cancer | [102] |
(E)-1-benzyl-5-bromo-3-{[1-(2,5-dimethoxyphenyl)-9H-pyrido[3,4-b]indol-3-yl]methylene}indolin-2-one |
| β-carboline derivative | Bax, PARP↑ Bcl-2↓ | Induce apoptosis | HCT-15 (IC50 = 1.43 ± 0.26 μM) | Colorectal cancer | [103] |
β-carboline-3-carboxylic acid (6u) |
| β-carboline derivative | Bcl-2↓ Cyt-C↑ | Induce apoptosis | A549 (IC50 = 5.61 ± 0.04 μM) | Lung cancer | [104] |
