Table 2.
Source, Mechanism of Action, Synergistic Interactions With Other Drugs, and Molecular Targets of Promising Natural Compounds
| Agent | Natural Source | Mechanism of Action | Organ Site | Synergistic Interaction | Molecular Targets |
|---|---|---|---|---|---|
| Green tea polyphenols and EGCG | Camellia sinensis (green tea) | Antioxidant, anti-mutagenesis, anti-proliferation (cell cycle arrest, apoptosis), anti-inflammation, anti-angiogenesis, immunomodulation | Skin, lung, oral cavity, head and neck, esophagus, stomach, liver, pancreas, small intestine, colon, bladder, prostate, mammary glands | Curcumin, erlotinib, luteolin, genistein, atorvastin, TRAIL, tamoxifen, celecoxib, cisplatin, sulindac, dacarbazine, adriamycin | p53, p73, p21, Bax, EGFR, AKT, NF-κB, Bcl-2, cyclin D1, COX-2, VEGF, MMP-2/9, STAT3, ERK1/2, AP-1, IL-12, CD8+ T-cell |
| Curcumin | Curcuma longa (turmeric powder) | Anti-oxidant, antiproliferation (cell cycle arrest, apoptosis), anti-inflammation, anti-angiogenesis, immunomodulation | Skin, lung, oral cavity, head and neck, esophagus, stomach, liver, pancreas, small intestine, colon, bladder, prostate, mammary glands, lymphoma, soft palate, cervix | Genistein, green tea, embelin, FU, vinca alkaloid, vinorelbine, gemcitabine, soy isoflavone, oxaliplatin, paclitaxel, TRAIL, celecoxib, retinoic acid | EGFR, IGF-1R, AKT, NF-κB, Bcl-2, COX-2, ERK, AP-1, Sp, VEGF, VEGFR1, MMP-2/9, p53, p21, Bax, STAT3/5 |
| Luteolin | Artichoke, broccoli, celery, cabbage, spinach, green pepper, pomegranate leaves, peppermint, tamarind, and cauliflower | anti-inflammation, anti-allergy, anti-proliferation (G1 and G2/M arrest, apoptosis), antioxidant, pro-oxidant | Ovarian, gastric, liver, colon, breast, oral, oesophageal adenocarcinoma, prostate, lung, nasopharyngeal, cervix, leukemia, skin, and pancreatic | Cisplatin, doxorubicin, TRAIL, TNF-α | JNK, p53, DR5, BAX, p21, PUMA, EGFR, IGF-1R, AKT, NF-κB, Bcl-2, CDK, ERK, STAT3 |
| Resveratrol | Red wine, grapes (mainly in the skin), mulberries, peanuts, vines, pines | Antioxidant, antiproliferation (cell cycle arrest and apoptosis), antiangiogenesis, antiinflammation | Ovarian, breast, prostate, liver, uterine, leukemia, lung, gastric | EGCG, indole-3-carbinol, vitamin E analogue, methylseleninic acid, quercetin, genistein, TRAIL, cisplatin, doxorubicin, ellagic acid, platinum compounds, FU, paclitaxel | SOD, catalase, glutathione, ↑glutathione, AKT, NF-κB, iNOS, COX-2, STAT3, survivin, p53, p21, BAX, BAK, DR |
| Genistein | Soybeans and soy products, red clover (Trifolium pretense), sicilian pistachio (Pistacia vera) | Antioxidant, antiproliferation (growth inhibition, cell cycle arrest, apoptosis), anti-angiogenesis, anti-inflammation | Prostate, breast, skin, colon, stomach, liver, ovary, pancreas, oesophagus, head and neck | EGCG, letrozole, docetaxel, arsenic trioxide, resveratrol, lycopene, vitamin D, tamoxifen, paclitaxel, cisplatin, erlotinib, gemcitabine, doxorubicin, FU, camptothecins, adriamycin, bleomycin | AKT, NF-κB, Bcl-2, survivin, cyclin D1, COX-2, MMP-2/9, p53, p21, GADD153, Bax, STAT3/5, ERK1/2, CDK1, AP-1, IGF-1R |
| Pomegranate | Punica granatum (pomegranate fruit, pomegranate juice, pomegranate seed and seed oil) | Antioxidant, antiproliferation (growth inhibition, cell cycle disruption and apoptosis), antiangiogenesis, anti-inflammation | Prostate, skin, breast, lung, colon, oral, leukemia | NF-κB, Bcl-2, COX-2, VEGF, ERK, JNK, p38, AKT, mTOR, iNOS, cyclin, CDK, p21, p27, BAX, BAK | |
| Lycopene | Tomatoes, guava, rosehip, watermelon, papaya, apricot and pink grapefruit; most abundant in red tomatoes and processed tomato products | Antioxidant, antiproliferation (growth inhibition, cell cycle arrest, apoptosis), anti-angiogenesis, anti-inflammation, immunomodulator | Prostate, lung, breast, gastric, liver, pancreas, colotectal, head and neck, skin | Genistein, adriamycin, cisplatin | Cyclin D1, Bcl-2, Bcl-xL, AKT, BAD, NF-κB, MMP-9, Sp-1, IGF-BP3 |
| Ellagic acid | Pomegranate juice, and seed oil, different nuts, blue honeysuckle (Lonicera caerulea), strawberries and other berries, bark of arjun (Terminalia arjuna), leaves and fruits of T. bellerica and bark, leaves and fruits of T. muelleri | Antioxidant, anti-proliferation (growth inhibition, cell cycle arrest, apoptosis), anti-inflammation | Neuroblastoma, skin, pancreas, breast, prostate, colon, intestine, esophagus, bladder, oral, leukemia, liver | Cisplatin, vinorelbine, quercetin, resveratrol, cyclosporine A, 6-gingerol, seleno-methionine | p53, p21, JNK, p38, ↓CDK2, glutathione, glutathione-peroxidase, catalase, SOD, NF-κB, COX-2, PDGF, VEGF, MMP-2/9 |
| Lupeol | Mango, olive, fig, strawberry, red grapes | Antioxidant, anti-mutagenesis, anti-inflammation, antiproliferation (cell cycle arrest, apoptosis, induction of differentiation | Skin, lung, leukemia, pancreas, prostate, colon, liver, head and neck | Cisplatin | 14-3-3-σ, BAX, p21, Fas, Bcl-2, cyclin D1/2, Ras, NF-κB, COX-2, NOS, AKT |
| Betulinic acid | Widely distributed in plant kingdom; most abundant sources are Betula spp (birch tree), Ziziphus spp, Syzigium spp, Diospyros spp, and Paeonia spp | Anti-inflammation, apoptosis, immunomodulation | Skin, ovary, colon, brain, renal cell carcinoma, cervix, prostate, leukemia, lung, breast, head and neck | Bleomycin, FU, irinotecan, oxaliplatin, doxorubicin, cisplatin, taxol, dactinomycin, TRAIL, vincristine | PPAR-γ, p21, p38, JNK, topoisomerase I, NF-κB, COX-2, Bcl-2, cyclin D1/3, ↓Sp1,3 and 4 |
| n-3 polyunsaturated fatty acids | Corn oil, sunflower oil, safflower oil, and olive oil, soybeans, walnuts, dark green leafy vegetables such as kale, spinach, broccoli, and brussels sprouts, and seeds or their oils such as flaxseed, mustard seed, and rapeseed (canola) | Anti-inflammation, apoptosis, cell cycle arrest, lipid peroxidation | Colorectal, prostate, breast, colon, gastric, pancreatic, head and neck, esophageal, hematologic malignancies | Sodium butyrate | NF-κB, Bcl-2, STAT3, p53, Bax, p21, Fas/FasL, PPAR-γ, RXR, Ras, ERK 1/2 |
| Ginkolide B | Ginko biloba | Antioxidant, anti-angiogenic, apoptosis | Ovary, breast, brain | Ethanol | PAFR, NO, iNOS, eNOS, JNK |
Abbreviations: EGCG, epigallocatechin-3-gallate; TRAIL, tumor necrosis factor–related apoptosis-inducing ligand; EGFR, epidermal growth factor receptor; NF-κB, nuclear factor-κB; COX-2, cyclo-oxygenase-2; VEGF, vascular endothelial growth factor; MMP-2/9, matrix metalloproteinases; IL-12, interleukin 12; FU, fluorouracil; IGF-1R, insulin-like growth factor-1 receptor; Sp, stimulating protein; VEGFR1, vascular endothelial growth factor receptor 1; TNF-α, tumor necrosis factor α; JNK, Jun-N-terminal kinase; CDK, cyclin-dependent kinase; ERK, extracelluar signal–regulated kinase; SOD, superoxide dismutase; mTOR, mammalian target of rapanycin; iNOS, inducible nitric oxide synthase; DR, death receptor; IGF-BP3, insulin-like growth factor binding protein 3; PPAR-γ, peroxisome proliferator-activated receptor-γ; PAFR, platelet activating factor receptor; NO, nitric oxide; eNOS, endothelial nitric oxide synthase.