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. 2022 Sep 16;12(9):1306. doi: 10.3390/biom12091306

Table 1.

Bioactive natural products against prostate cancer.

Natural Compound Constituent Plant Source Chemical Structure Mechanism Molecular Pathway (Reference) In Vitro In Vivo
1. Polyphenol
1. 1 Polyphenol Flavonols
1.1.1 Quercetin Flavonol Apple and onion graphic file with name biomolecules-12-01306-i001.jpg Induction of apoptosis. PI3K/Akt and MAPK/ERK [6]; p21, FA, Hsp90 [7]. LNCaP, DU 145, PC-3, Prostate cancer stem cells.
1.1.2 Apigenin Flavone Anthemis sp. graphic file with name biomolecules-12-01306-i002.jpg Induction of apoptosis and cell cycly arrest. IGF-IR; PI3k/Akt [8]; HDACs [9]; ROS [10]; VEGF [11]. PC-3 and 22Rv1. 22Rv1 and PC-3 xenografts.
1.1.3 Baicalin Flavone Genus Scutellaria graphic file with name biomolecules-12-01306-i003.jpg Inhibition of proliferation and induction of apoptosis. Caveolin-1/AKT/mTOR [12]; AR target genes [13]; Ezrin [14]. DU 145 and PC-3. PC-3 xenografts.
1.1.4 Cyanidin-3-glucoside Flavonoid anthocyanin Berries, red cabbages, teas, and coloured grains. graphic file with name biomolecules-12-01306-i004.jpg Inhibition of EMT. Snail/E-cadherin [15]. PC-3.
1.1.5 Daidzein Isoflavone Soybeans graphic file with name biomolecules-12-01306-i005.jpg Induction of cell cycle arrest; CpG island demethylation. CDK [16]; GSTP1 and EPHB2 [17]; ERβ [18]. DU 145, LNCaP and PC-3.
1.1.6 Delphinidin Flavonoid anthocyanin Viola sp. graphic file with name biomolecules-12-01306-i006.jpg Inhibition of cell growth; Induction of apoptosis. NF-κB [19]; β-catenin [20]; DR5 [21]; HDAC [22]. PC-3 and LNCaP. PC-3 xenografts.
1.1.7 Epigallocatechin-3-gallate (EGCG) Catechin Green tea graphic file with name biomolecules-12-01306-i007.jpg Suppression of the proliferation, invasion and migration, and vasculogenic mimicry; Induction of apoptosis and autophagy. ERK1/2 [23], VEGF, uPA, angiopoietin 1/2, MMP-2, and MMP-9 [24], PSA [25], Caspase 9 [26]; Twist/VE-Cadherin/AKT [27]; AR [28]; CHOP and p-eIF2α [29]. LNCaP, PC-3, 22Rv1. PC-3 xenografts.
1.1.8 Fisetin Flavonol Acacia greggii graphic file with name biomolecules-12-01306-i008.jpg Inhibition of adhesion, migration, and metastasis; Induction of autophagy. NF-κB [30]; mTOR and PI3K/Akt [31]; AR [32]; NF-κB [33]; Nudc [34]. DU 145, LNCaP, PC-3. CWR22 Rupsilon1 cells xenograft.
1.1.9 Formononetin (FN) Omethylated isoflavone Trifolium pretense. graphic file with name biomolecules-12-01306-i009.jpg Induction of apoptosis. ERK1/2, MAPK-Bax [35]; IGF-1/IGF-1R [36]; p38/Akt [37]; RASD1 [38]. LNCaP, PC-3, and DU 145.
1.1.10 Genistein Flavanone Glycine max graphic file with name biomolecules-12-01306-i010.jpg Inhibition of the proliferation;
Suppression of cancer stem cells; Activation of epigenetic modification; Induction of apoptosis.		 IGF-1/IGF-1R [39]; miR-1260b [40]; miR-34a and HOTAIR [41]. LNCaP, PC-3, and DU 145. TRAMP mice.
1.1.11 Glycyrrhiza
1.1.11.1 Isoangustone A Flavonoid Glycyrrhiza uralensis graphic file with name biomolecules-12-01306-i011.jpg Induction of apoptosis; G1 phase arrest. Caspase [42]; CDK2/4, cyclin A [43]. DU 145.
1.1.11.2 Licoricidin Flavonoid Glycyrrhiza uralensis graphic file with name biomolecules-12-01306-i012.jpg Inhibition of metastasis and invasion. MMP, TIMP-1, VEGF [44]. DU 145.
1.1.12 Licochalcone Flavonoid Licorice root graphic file with name biomolecules-12-01306-i013.jpg Induction of G2/M phase arrest and apoptosis. Cyclin B1 and cdc2 [45]. LNCaP, PC-3.
1.1.13 Luteolin Flavone Terminalia chebula graphic file with name biomolecules-12-01306-i014.jpg Suppression of angiogenesis; Induction of cell cycle arrest. IGF-1 [46]; VEGF-2R, AR [47]. LNCaP and PC-3. PC-3 xenografts.
1.2 Polyphenol lignans
1.2.1 Arctigenin lignan Arctium lappa graphic file with name biomolecules-12-01306-i015.jpg Inhibition of the proliferation; Induction of apoptosis and autophagy. AR [48], FFA [49], PI3K/Akt/mTOR [50]. LAPC-4 and LNCaP. LAPC-4 xenograft.
1.2.2 Honokiol Lignin Magnolia officinalis graphic file with name biomolecules-12-01306-i016.jpg Induction of G0-G1 phase arrest and apoptosis; Inhibition of angiogenesis. Bax, Bak, Bad, Bcl-xL, and Mcl-1 [51,52]. LNCaP, PC-3, and C4-2. PC-3 xenografts.
1.2.3 Magnolol Hydroxylated biphenyl lignan Magnolia officinalis graphic file with name biomolecules-12-01306-i017.jpg Induction of apoptosis and inhibition of the adhesion, invasion, and migration. EGFR [53]. PC-3.
1.2.4 Obovatol Biphenyl ether lignan Magnolia obovate graphic file with name biomolecules-12-01306-i018.jpg Induction of apoptosis. NF-κB [54]. LNCaP and PC-3.
1.2.5 Silibinin Flavolignan Silybum marianum graphic file with name biomolecules-12-01306-i019.jpg Induction of G1 phase arrest; Induction of apoptosis; Inhibition of EMT; Restriction of tumor microvessel density. p21 and p27 [55]; NF-κB [56]; ZEB1 and SLUG [57]. DU 145. PC-3 xenografts and TRAMP mice [58].
1.3 Polyphenol Stilbenoids
1.3.1 Resveratrol Stilbenoid Grape, raspberry, mulberry. graphic file with name biomolecules-12-01306-i020.jpg Induction of apoptosis; Cellular antioxidant defense. FKHRL1 [59]; VEGF, MMPs [60]; CXCR4 [61]; ROS, RNS, HO-1 [62]; AR [63]. TRAMP mouse [61].
1.4 Other Polyphenols
1.4.1 Curcumin Polyphenols Curcuma longa graphic file with name biomolecules-12-01306-i021.jpg Induction of apoptosis; Induction of autophagy. EGF-R [64]; AIF [65]; Wnt/β-catenin [66]; Nrf-2 [67]; MMPs [68]. DU 145, LNCaP and PC-3. LNCaP xenograft [69]; DU 145 xenografts [68].
1.4.2 Ellagitannins Polyphenols Pomegranate fruit graphic file with name biomolecules-12-01306-i022.jpg Induction of apoptosis and S phase cell cycle arrest; Inhibition of metastasis and angiogenesis. SIRT1, p21, AIF [70]; Eicosanoid [71]; cyclin B1 and D1 [72]. MMP-2 [73]; p53-MDM2 [74]. LNCaP, 22RV1 and PC-3. murine studies [75].
1.4.3 Gallic acid Polyphenols Grape seed graphic file with name biomolecules-12-01306-i023.jpg Induction of G2/M cell cycle arrest; Induction of apoptosis; Inhibition of invasion and migration. cdc25A/C-cdc2 [76]; PARP [77]; p38, JNK, PKC, and PI3K/AKT [78]; Cdk, cyclin B1, and E [79]. DU 145; PC-3. TRAMP mice [79]; DU 145 and 22Rv1 xenografts [80].
1.4.4 Gossypol Polyphenolic aldehyde Cotton seed graphic file with name biomolecules-12-01306-i024.jpg Induction of G0/G1 phase arrest; Induction of apoptosis; Induction of autophagy; Inhibition of angiogenesis; Reduction of the microvessel density. TGF-β1 and Akt [81]; Bcl-xL [82]; Beclin1 [83]. AP-1, NF-κB [84]. MAT-LyLu; PC-3. PC-3 xenografts [85].
2. Terpenoids
2.1 Artemisinin Sesquiterpene Artemisia annua graphic file with name biomolecules-12-01306-i025.jpg Induction of G1 cell cycle arrest; Inhibition of viability. CDK4 and Sp1 [86], caspases 8/9 [87]. LNCaP, DU 145 and PC-3.
2.2 Betulinic Acid (BA) Triterpene Betula papyrifera graphic file with name biomolecules-12-01306-i026.jpg Induction of apoptosis; Inhibition of angiogenesis. Bax/Bcl-2 [88], DUBs [89], AR and cyclin D [90]. DU 145, LNCaP, and PC-3. TRAMP mice [90].
2.3 Germacrone Sesquiterpene Geranium macrorrhizum. graphic file with name biomolecules-12-01306-i027.jpg Induction of apoptosis and autophagy. Akt/mTOR [91]. PC-3 and 22RV1.
2.4 Ginsenosides Steroid glycosides and triterpene saponins Genus Panax graphic file with name biomolecules-12-01306-i028.jpg Inhibition of proliferation; Inhibition of migration and metastasis; Induction of apoptosis. p38 [92]; MAP [93]. PC-3M, LNCaP and PC-3. PC-3 xenograft [94].
2.5 Glycyrrhizin Saponins Fabaceae graphic file with name biomolecules-12-01306-i029.jpg Induction of apoptosis and autophagy. Apoptosis and autophagy [95]. PC-3.
2.6 Lycopene Carotenoid Tomatoes graphic file with name biomolecules-12-01306-i030.jpg Reduction in cholesterol synthesis; Induction of apoptosis. CDK7, EGFR, IGF-1R, and BCL2 [96]; PPARγ-LXRα-ABCA1 [97]; CDK7,EGFR, IGF-1R, BCL2 [96]; IGF-I, IGF-IR, and IGFBP-3 [98]. LNCaP, PC-3 and DU 145. PC-3 xenograft [98]; TRAMP mice [99].
2.7 Oridonin Isoprenoid Rabdosia rubescens graphic file with name biomolecules-12-01306-i031.jpg Induction of apoptosis and G0/G1 cell cycle arrest; Induction of apoptosis, autophagy, and G2/M phase arrest. p53 and Bax [100]; p21 [101]. LNCaP and PC-3.
2.8 Thymoquinone (TQ) Monoterpene Nigella sativa graphic file with name biomolecules-12-01306-i032.jpg Induction of apoptosis; Inhibition of angiogenesis. AR and E2F-1 [102]; ROS [103]; AKT, VEGF [104]. LNCaP, PC-3, C4-B, and DU 145.
2.9 Ursolic acid (UA) Pentacyclic triterpenoid Cornus Officinalis graphic file with name biomolecules-12-01306-i033.jpg Induction of apoptosis. Akt and MMP9 [105]; JNK [106]; CXCR4 [107]. NF-κB and STAT3 [108]; PC-3, LNCaP, LNCaP-AI, and DU 145. TRAMP mice [108].
2.10 β-Elemonic acid Triterpene Ganoderma tsugae, lucidum, and Boswellia. graphic file with name biomolecules-12-01306-i034.jpg Induction of apoptosis. JAK2/STAT3/MCL-1 and NF-κB [109]. 22RV1. 22RV1xenograft [109].
3. Taxanes
3.1 Cabazitaxel Taxane European yew tree graphic file with name biomolecules-12-01306-i035.jpg Inhibition of proliferation. P-gp [110]. C4-2.
3.2 Docetaxel Taxane European yew tree graphic file with name biomolecules-12-01306-i036.jpg Induction of apoptosis. p38/p53/p21 [111]. LNCaP, PC3 and DU 145.
3.3 Paclitaxel Taxane Pacific yew tree graphic file with name biomolecules-12-01306-i037.jpg Induction of apoptosis. Bcl-2 [112]; AR [113]. C4-2. 22Rv1 xenografts [113].
4. Alkaloids
4.1 Anibamine, Pyridine quaternary alkaloid Aniba sp. graphic file with name biomolecules-12-01306-i038.jpg Inhibition of proliferation. CCR5 [114]. LNCaP.
4.2 Berberine Isoquinoline Alkaloid Genus Berberis graphic file with name biomolecules-12-01306-i039.jpg Induction of G1 phase arrest; enhancement of the radiosensitivity. p53-p21 [115], AR [116], MAPK/caspase-3 and ROS [117]. RM-1. LNCaP xenografts [116].
4.3 Capsaicin Alkaloid Red pepper graphic file with name biomolecules-12-01306-i040.jpg Induction of apoptosis. JNK and ERK [118]. p53, p21, and Bax, AR [119]. LNCaP, PC-3, and DU 145.
4.4 Neferine Bisbenzylisoquinoline alkaloid Nelumbo nucifera graphic file with name biomolecules-12-01306-i041.jpg Inhibition of proliferation and migration of prostate cancer stem cells. p38 mapk/jnk [120]. PC3.
4.5 Piperine Alkaloid Black pepper graphic file with name biomolecules-12-01306-i042.jpg Induction of apoptosis, autophagy, and G0/G1 phase arrest. NF-kB, STAT-3 [121]. LNCaP, PC-3, and DU 145. Animal xeno-transplanted model [122]; CRPC xenograft model [123].
4.6 Sanguinarine Alkaloid Sanguinaria Canadensis graphic file with name biomolecules-12-01306-i043.jpg Inhibition of ubiquitin-proteasome system. Stat3 [124], survivin [125], RGS17 [126]. DU 145, C4-2B, and LNCaP. DU 145 xenografts [125].
5. Other
5.1 Gambogic acid Xanthone Garcinia hanburyi graphic file with name biomolecules-12-01306-i044.jpg Inhibition of angiogenesis. PI3K/Akt and NF-κB [127]; VEGF-2R [128]. PC-3. PC-3 xenograft model [128].
5.2 Glucoraphanin → Thiocyanates + Isothiocyanates + Indoles
5.2.1 Sulforaphane (SFN) Isothiocyanates (ITCs) Cruciferous vegetables graphic file with name biomolecules-12-01306-i045.jpg Induction of apoptosis; Induction of G2/M cell cycle arrest; Inhibition of FA metabolism. ERK1/2 [129]; Hsp90 [130]; AR [131]; ROS [132]; FA [133]; HDACs [134]. LNCaP, DU 145 and PC-3. TRAMP mice [134].
5.2.2 Phenethyl-Isothiocyan (PEITC) Isothiocyanates (ITCs) Cruciferous vegetables graphic file with name biomolecules-12-01306-i046.jpg Induction of G2/M cell cycle arrest; Induction of apoptosis; Inhibition of angiogenesis. α- and β-tubulin [135]; Bax [136]; Akt [137]; PECAM1-CD31 [138]. C4-2B, DU 145, PC-3, and LNCaP. LNCaP xenograft model [138]; TRAMP mice [139].
5.2.3 Indole-3-Carbinol Indoles Cruciferous vegetables graphic file with name biomolecules-12-01306-i047.jpg Induction of apoptosis and cell cycle arrest; Modulation of epigenetic alterations of cancer stem cells. Bax [140]; NF-ĸB, Nrf2 [140]. LNCaP, and PC-3.