Table 1.
Natural phytocompounds and herbal medicines in the treatment of cutaneous melanoma.
| Phytochemicals | Mode of actions/targets | References |
|---|---|---|
| Phenolics | ||
| catechins (-)-epigallocatechin-3-gallate (EGCG) (single or in combination with IFN α-2b or dacarbazine) |
anti-proliferative and proapoptotic effects Fas/FasL signaling pathway, Bax, caspases-3, -7 and -9 ↑ tumor growth, metastasis, cell spreading, cell-extracellular matrix, MMP-9, FAK ,NF-κB pathway, and Bcl-2 ↓ |
[58,59,60,61,62,72] |
| resveratrol | NQO2 and p53 ↑; cell proliferation ↓ | [65,66] |
| piceatannol | arrest at cell cycle G2 phase; cyclins A, E, and B1 ↓ | [67] |
| curcumin | anti-proliferative and proapoptotic effects; caspase-3 ↑ tumor growth, metastasis, NF-κB, COX-2, MMP, and PRL-3 ↓ |
[69,70,71,72] |
| apigenin, quercetin, and kaempferol | Bcl-2, p27, and p21 ↑ tumor growth, invasion, metastasis, CDK1, and CDK2 ↓ |
[73,74] |
| genistein plus cisplatin | Apaf-1 ↑; Bcl-2 and Bcl-xL ↓ | [77] |
| Alkaloids | ||
| punarnavine | immune response, IL-2, and IFN-γ ↑ metastasis, IL-1β, IL-6, TNF-α, MMP-2, MMP-9, ERK-1, ERK-2, and VEGF ↓ |
[78,79] |
| 9-carbethoxy-3-methylcarbazole, 9-formyl-3-methylcarbazole 1-O-acetylnorpluviine, sternbergine 1-epideacetylbowdensine, crinamine, crinine, hamayne, lycorine, anhydrolycorin-6-one |
cytotoxic to melanoma cells | [80,81] |
| matrine | anti-proliferative and apoptotic effects; invasion, metastasis, and heparanase ↓ | [107] |
| ligusticum | metastasis, CD34, and VEGF ↓ | [108] |
| berberine | anti-proliferative and necrotic effects tumor growth ↓ | [109] |
| Terpenoids | ||
| 13-cis-retinoic acid (13-cis-RA), all-trans-retinoic acid (ATRA) (or in combination with cisplatin and 5-fluorouracil) |
anti-proliferative and anti-invasive effects lung metastatic melanoma ↓ |
[83] |
| β-carotene | caspases-3, -8 and -9 , cytochrome c release, and t-BID ↑; Bcl-2 ↓ | [84] |
| lycopene | PDGF-BB and cell migration of stromal fibroblasts ↓ | [85] |
| ginsenoside-Rh2 (G-Rh2) | apoptotic effect; caspase-3 and caspase-8 pathway ↑ | [105] |
| oridonin | anti-proliferative and apoptotic effects EGFR, Grb2, Ras, and Raf-1 ↓ |
[110,111] |
| triptolide | tumor growth and cell proliferation ↓ | [112] |
| Galactolipid & polyunsaturated fatty acids | ||
| 1,2-di-O-α-linolenoyl-3-O-β-galactopyranosyl-sn-glycerol (dLGG) | tumor growth, NF-κB, NO, iNOS, COX-2, and PGE2 ↓ | [92] |
| n-3 PUFAs | PTEN pathway ↑; angiogenesis and metastasis ↓ | [95,96] |
| Plant hormone | ||
| jasmonic acid (JA) | tumor growth and metastasis ↓ | [99] |
| methyl jasmonate (MJ) | apoptotic effect; caspase-3 ↑ | |
| Xanthone | ||
| gambogic acid | anti-proliferative effect; Bax/Bcl-2 ratio and caspase-3 ↑ | [106] |
| Isothiocyanates | ||
| sulforaphane (SFN) | apoptotic effect; IL-2, and IFN-γ ↑ tumor growth, invasion, metastasis, MMP, IL-1β, IL-6, TNF-α, and GM-CSF ↓ |
[101,102] |
| Vitamins | ||
| γ-tocotrienol (γ-T3) (single or in combination with docetaxel and dacarbazine) |
anti-proliferative and anti-invasive effects E-cadherin, γ-catenin, caspases-3, -7 and -9 ↑ Id-1, Id-2, EGFR, NF-κB p65, Snail, twist, α-SMA, and vimentin ↓ |
[103] |
| vitamin C (ascorbic acid) | p38 MAPK, IGF II, IGF-IR, and COX-2 ↓ | [104] |
↑: up-regulation or activation; ↓: down-regulation or inhibition.