Table 1 Summary of current therapeutic strategies for some natural products and their chemical derivatives in GSCs. The structure, biological targets, analysis methods, clinical phase andchanism of 38 natural compounds/or derivatives are described
Compound | Therapeutic/structure | Biological targets/mechanism of action | Evaluated | Clinical trials | Ref. |
|---|---|---|---|---|---|
1 | Cyclopamine (11-deoxojervine)
| Target Hedgehog pathway. Promote inhibition of side and aldefluor-positive populations. | In vitro and in vivo | No | PubChem CID: 442972 |
2 | Guggulsterone
| Promote intrinsic apoptosis of GSCs and sensitize cells to SANT-1. Targeting Ros/NF-κB and Hedgehog. | In vitro | No | PubChem CID: 6450278 |
3 | CX-4945 (Silmitasertib)
| Target several GSC factors and markers Casein kinase 2 selective inhibitor. | In vitro and in vivo | Yes | PubChem CID: 24748573 |
4 | SCH 900776
| DNA repair inhibitors Promote radio-chemosensitivity. Promote CHK1 inhibition. | In vitro and in vivo | Yes | PubChem CID: 46239015 |
5 | SAR-020106
| DNA repair inhibitor Promote CHK1 inhibition | In vitro and in vivo | Yes | PubChem CID: 44203948 |
6 | AZD7762
| DNA repair inhibitor Promote radio-chemosensitivity. Promote CHK1, CHK2, and ATM protein inhibition. | In vitro and in vivo | Yes | PubChem CID: 11152667 |
7 | Debromohymenialdisine (DBH)
| DNA inhibitors Promote radio-chemosensitivity. Promote CHK1, CHK2, and ATM protein inhibition. | In vitro and in vivo | Yes | PubChem CID: 135451156 |
8 | Erlotinib
| EGFR inhibitors Promote proliferation and self-renewal inhibition. Promote cell death. | In vitro and in vivo | Yes | PubChem CID: 176870 |
9 | Gefitinib
| EGFR inhibitors Promote proliferation and self-renewal inhibition. Promote cell death. | In vitro and in vivo | Yes | PubChem CID: 123631 |
10 | Rapamycin (Sirolimus)
| Promote GSC differentiation. Reduce stem cell markers. Promote radiosensitivity. | In vitro and in vivo | Yes | [36, 67, 69, 97, 130, 133,134,135] PubChem CID: 5284616 |
11 | Chloroquine (CQ)
| Promote radiosensitivity Inhibit autophagy process. | In vitro and in vivo | Yes | PubChem CID: 2719 |
12 | Cilengitide
| Promote αv integrin inhibition. Promote GSCs autophagy, cytotoxicity, and cell death Promote radiosensitivity. | In vitro and in vivo | Yes | [138] PubChem CID: 176873 |
13 | AZD2014 (Vistusertib)
| Promote mTORC1/2 inhibition. Promote radiosensitivity. Promote DNA double-strand break repair inhibition. | In vitro and in vivo | Yes | PubChem CID: 25262792 |
14 | Eckol
| Promote radiosensitivity and TMZ sensitivity. Reduce neurosphere formation and stem cell markers Target PI3-kinase-Akt and Ras-Raf-1-Erk signaling pathways. | In vitro and in vivo | No | [107] PubChem CID: 145937 |
15 | Nordy
| Promote GSC differentiation. Reduce proliferation, stem cell markers, and self-renewal Target ALOX5 | In vitro and in vivo | No | [108] PubChem CID: 319062914 |
16 | Resveratrol
| Promote radiosensitivity and differentiation of GSCs. HIF inhibitor. Induce apoptosis of CD133+ cells. Target STAT3 pathway | In vitro and in vivo | No | PubChem CID: 445154 |
17 | STX-0119
| Promote inhibition of GSCs proliferation. Reduce stem cell markers. STAT3 inhibitor. | In vitro and in vivo | Yes | [142] PubChem CID: 4253236 |
18 | ER400583-00
| HIF inhibitors Reduce neurosphere formation and stem cell markers Inhibit VEGF signaling Promote microenvironment modulation. Reduce HIF-1 expression. | In vitro and in vivo | No | [57, 106, 111, 143,144,145,146,147,148] Not available on PubChem |
19 | WP1193
| Analog of natural product caffeic acid benzyl ester Reduce proliferation and stem cell markers Induce apoptosis Promote G1 arrest decrease of cyclin D1 and p21(Cip1/Waf-1) increase Inhibit JAK2/STAT3 | In vitro and in vivo | No | [112] Not available on PubChem |
20 | All-trans-retinoic acid (Vitamin A acid)
| Promote differentiation Reduce proliferation and nestin stem cell markers Promote apoptosis Target ERK1/2 signaling | In vitro and in vivo | No | PubChem CID: 444795 |
21 | Tanshinone IIA
| Promote suppression of GSC proliferation. Reduce stem cell markers. Promotes the increase of GSCs differentiation markers. Induce GSCs apoptosis. Reduce the IL6/STAT3 signaling pathway. | In vitro and in vivo | No | [155] PubChem CID: 164676 |
22 | Oleanolic acid
| Promote suppression of JAK-STAT3 activation in M2 polarization of tumor-associated macrophages. | In vitro | No | [156] PubChem CID: 10494 |
23 | WP1066
| Promote STAT3 inhibition Decrease the surviving fraction of GSC | In vitro and in vivo | Yes | Not available on PubChem |
24 | Bevacizumab >Bevacizumab light chain DIQMTQSPSSLSASVGDRVTITCSASQDISNYLNWYQQKPGKAPKVLIYFTSSLHSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYSTVPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >Bevacizumab heavy chain EVQLVESGGGLVQPGGSLRLSCAASGYTFTNYGMNWVRQAPGKGLEWVGWINTYTGEPTYAADFKRRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCAKYPHYYGSSHWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | Promote disruption of vascular niche and reduce tumor proliferation. Promote radiosensitivity. Reduce proliferation and block GSC ability to induce endothelial cell migration. VEGF inhibitor | In vitro and in vivo | Yes | [113, 124, 132, 159,160,161,162,163] DrugBank: DB00112 |
25 | Cediranib (AZD2171)
| Promote disruption of the vascular niche and reduce tumor proliferation. Promote radiosensitivity. Reduce proliferation and block GSC ability to induce endothelial cell migration. VEGF inhibitor | In vitro and in vivo | Yes | PubChem CID: 9933475 |
26 | Honokiol
| Promote PI3K/mTOR signaling inhibition. Promote proliferation inhibition of side positive populations. Promote TMZ-resistant cell sensitivity. Promote DNA double-strand break repair inhibition. | In vitro and in vivo | Yes | PubChem CID: 72303 |
27 | Manassantin B
| Target hypoxia-inducible factor-1. | In vitro | No | [111] PubChem CID: 10439828 |
28 | Curcumin
| Induce GSCs apoptosis. Target hypoxia-inducible factor-1. | In vitro and in vivo | No | PubChem CID: 969516 |
29 | SU5416 (Semaxinib)
| Reduce neurosphere formation and stem cell markers Reduce HIF-1 expression Inhibit VEGF signaling Target PI3K/AKT/p70S6K1 signaling pathway | In vitro and in vivo | No | [147] PubChem CID: 5329098 |
30 | Cannabinoids therapies
| Promote differentiation. Inhibit gliomagenesis. Target cannabinoid type 1 (CB1) and type 2 (CB2) receptors. | In vitro and in vivo | No | [157] PubChem CID: 9852188 |
31 | Vorinostat (SAHA)
| Promote GSC differentiation. Promote G1/S arrest of GSCs. Inhibit histone deacetylases (HDACs). | In vitro and in vivo | Yes | PubChem CID: 5311 |
32 | Sahaquine
| Promote HDAC inhibition Reduce GSC viability Reduce invasiveness | In vitro | No | [138] Not available on PubChem |
33 | VX680
| Pan-AURK inhibitor Induce apoptosis Reduce tumor growth | In vitro and in vivo | No | [172] PubChem CID 5494449 |
34 | MLN8237 (Alisertib)
| Promote GSC colony formation inhibition. Promote radiosensitivity and TMZ sensitivity. Aurora-A kinase inhibitor. | In vitro and in vivo | No | PubChem CID: 24771867 |
35 | Metformin
| Promote inhibition of GSC self-renewal. Reduce GSC viability. Promote inhibition of CD133+ proliferation. | In vitro and in vivo | No | PubChem CID: 4091 |
36 | Telomestatin
| Polyketide component Induce apoptosis and impair the migration potential of GSCs. Promote telomeric and nontelomeric DNA damage in GSCs. | In vitro and in vivo | No | [182] PubChem CID: 443590 |
37 | Harmine
| Alkaloid component Promote self-renewal inhibition. Promote GSC differentiation. Promote neurosphere formation inhibition. | In vitro and in vivo | No | [183] PubChem CID: 5280953 |
