Family names Medical plants Compounds/extracts Dose/duration Target molecules and additional efficacy Cell lines References Hypericaceae Hypericum perforatum L. (H. perforatum) Hyperforin (HP), polyphenolic procyanidin B2 (PB-2), hypericin (HY) HP 20 µ M for 24 h PB-2 80 µ M for 24 h (Annexin V-binding analysis) Annexin V positive cells LN229 [21 ] Apiaceae Angelica sinensis n-Butylidenephthalide (BP) 75 µ g/mL for 6, 12, 24 h (cell cycle analysis) 75 µ g/mL for 24, 48, 72 h (Cell Death Detection Kit, POD) 75 µ g/mL for 0, 1.5, 3, 6, 12, 24, 48 h (Western blot analysis) DBTRG-05MG, DBTRG 8401 (human) ↑p53, p16, Bax, AIF protein induce Fas expression, caspase-8 (dose-dependent), procaspase-9, procaspase-3 ↓cdk2, cdk4, cdk6, cyclin D1, cyclin E, RG2 (rat) ↑p27, Bax, AIF induce Fas expression, caspase-8 (maximum expression at 24 h), procaspase-9, procaspase-3 ↓cdk2, cdk4, cdk6, cyclin D1, cyclin E, p21 cell cycle arrest (G0-G1 phase) DBTRG-05MG, GBM 8401 (human), RG2 (rat) [22 ] Ericaceae Vaccinium macrocarpon (cranberry)Flavonoid-rich fraction 6 (Fr6), proanthocyanidins (PAC) fraction Fr6 concentration: 0, 50, 100, 150, 200, 250, 300 mg/L for 24 and 48 h (cell cycle distribution analysis) (Annexin V, PI) PAC concentration: 0, 20, 40, 60, 80, 100, 120, 140, 160 mg/L for 24, 48 h (cell cycle distribution analysis) (Annexin V, PI) ↑G1 phase ↓S phase cell cycle arrest (G1 phase) U87MG [23 ] Menispermaceae Tinospora cordifolia Ethanol extract 250 μ g/ml, 350 μ g/ml for 72 h ↑GFAP, NCAM, ↓MMP-2,9, cyclin D1, Bcl-xl C6, U87 MG [24 ] Ranunculaceae Nigella sativa Thymoquinone 20 μ M, 40 μ M for 24 h ↑p62, cathepsin B T98G, U87 MG [25 ] Niclosamide 1.5 μ m/L for 48 h ↓WNT/CTNNB1-, NOTCH-, mTOR-, NF-kB LN229, T98G, U87MG, U138, and U373 MG [26 ] Fabaceae Caesalpinia sappan Brazilin 10 μ g/ml, 15 μ g/ml, 20 μ g/ml for 24 h ↑PARP ↓caspase-3, caspase-7 U87 MG [27 ] Cannabaceae Marijuana (cannabis) Δ(9)-Tetrahydrocannabinol (THC) and cannabidiol (CBD) 75 mg MPs (biodegradable polymeric microparticles) every 5 days ↓KI67, CD31 U87 MG [28 ] Hopeaphenol, r2-viniferin 20 μ g/ml (hopeaphenol), 100 μ g/ml (r2-viniferin) for 120 h ↓caspase-9, caspase-3/7 D-GBM [29 ] Lamiaceae Scutellaria baicalensis Wogonin 0–100 μ M for 24 h ↑ AMPK, p53 ↓mTOR, 4E-BP1 G0/G1 phase arrest U87 MG, U343 MG, U373 MG, T98G, MCF-10A [30 ] Rosaceae Aronia melanocarpa Chokeberry extract, curcumin 10 μ g/ml (curcumin), 50 μ g/ml (polyphenolics from Aronia melanocarpa) ↓MMP-2, -14, -16, -17 U373 MG [31 ] (1) Fabaceae (2) Polygonaceae (3) Lamiaceae (4) Asteraceae (5) Rutaceae (6) Dioscoreaceae (1) Sophora tonkinensis (2) Polygonum bistorta (3) Prunella vulgaris (4) Sonchus brachyotus (5) Dictamnus dasycarpus (6) Dioscorea bulbifera ZSP (Zeng Sheng Ping) 0, 50, 100 mg/kg/day ↓notch 2, Hes1, CD133 U87 MG, HSR-GBM1 JHH-GBM10, JHH-GBM14 [32 ] Acanthaceae Andrographis paniculata Andrographolide 10 μ M ↓PI3K/AKT, caspase-3 G2/M phase arrest U251, U87 MG [33 ] Macaranga schweinfurthii 3-Deoxyschweinfurthin B (3dSB), 3-deoxyschweinfurthin B-like p -nitro-bis-stilbene (3dSB-PNBS) 3dSB (500 nM), 3dSB-PNBS (500 nM), DMP-PNBS (1 M), or Y-27632 (10 M) for 48 h ↑PARP, GRP78, PDI ↓caspase-9 SF-295 [34 ] Asteraceae Artemisia argyi Jaceosidin 100 μ M/L for 24 h ↑p53, Bax, cytochrome c, caspase-3 G2/M phase arrest U87 MG [35 ] Resveratrol 30 μ M for 48 h ↑ Atg5, beclin-1, LC3-II, PI3k class III ↓CD133, OCT4, mTor/AKT/p70S6K S-G2/M phase arrest U-87 MG, U-251, U-138 MG [36 ] Asteraceae Tithonia diversifolia Tagitinin C 10 μ g/mL for 12 h ↑PARP, p-p38, ULK1, LC3-II U373 MG [37 ] Apiaceae Angelicasinensis (Z)-N-(2-(Dimethylamino)ethyl)-2-(3-((3-oxoisobenzofuran-1(3H)-ylidene)methyl)phenoxy)acetamide (PCH4) 50 µ g/ml for 24 h ↓Nur77, JNK DBTRG-05MG, GBM 8401 [38 ] Clusiaceae Garcinia mangostana γ -Mangostin80 μ M for 8 h ↑NK cell, ROS ↓PGE2, COX-2, NO U87 MG, GBM 8401 [39 ] High-fiber foods (such as corns, cereals, legumes, nuts, oil seed, soybean) Inositol hexaphosphate (IP6) 0.5, 1 mM for 24 h ↑Bax, Bax: Bcl-2 ratio, cytosolic level of cytochrome c, Smac/Diablo (in the cytosol), 80 kD calpain, caspase-9, 85 kD PARP fragment ↓cytochrome c, Smac/Diablo, Bcl-2, BIRC-2, hTERT T98G [40 ] Anacardiaceae Spondiaspinnata Methyl gallate 1 to 30 μ g/ml for 48 h ERK1/2 activation, apoptosis U87MG [41 ] Rutaceae Rutagraveolens L.R . graveolens a.e.1 mg/ml for 24, 48, 72 hours ERK1/2, AKT activation, apoptosis in A1 mes-c-myc cells U87MG, C6, U138 [42 ] Lamiaceae Rabdosiarubescens Oridonin 5 μ M for 12 h ↓RNA transferation, RanGTP U87MG [43 ] Berberidaceae Dysosmaversipellis Deoxypodophyllotoxin (DPT) 30 nM for 72 h ↓Cdc2, cyclin B1, Cdc25c U87MG, SF126 [44 ] Primulaceae Ardisiapusilla A.DCArdipusilloside I (ADS-I) (20 μ L, 5 mg/mL) for 4 h ↓vascular endothelial growth factor, C-reactive protein, tumor necrosis factor-α , interleukin-6, interleukin-2 rat C6 glioma cells (in vivo) [45 ] Curcuma Curcumaamada Roxb.Supercritical CO2 extract of mango ginger (CA) 0–100 mg/mL for 48 h ↓STAT3, Bcl-2, mutant p53 expression ↑ratio of Bax/Bcl-2 U87MG [46 ] Curcumin, temozolomide 7.5 μ M for 72 h ↓phosphorylation of cyclin B1, cyclin D1 G2/M arrest C6, U251MG U87MG [47 ] Rubiaceae Hedyotisdiffusa WilldHDW extract 0, 4, 8 mg/ml for 24 h ↓Bcl-2/Bax ratio, AKT suppression ↑caspase-3, Bcl-2, Bax and ERK S/G2-M phase arrest, MMP collapse U87MG [48 ] Berberidaceae Epimediiherba Icariin 0, 5, 10, 20 μ M for 2 h ↓NF-kB, piwil4, Rac1 vasodilator-stimulated phosphoprotein (VASP) U87MG [49 ] Hispidulin 10 μ M for 2 h ↓Bcl2 ↑AMPK G2 cell cycle arrest Human GBM SHG44 [50 ] Oleaceae Oleaeuropaea Olea europaea leaf extract (OLE) 1 mg/ml, 2 mg/ml for 24 h ↑ miR-153, miR-145, miR-137 T98G, U-138MG, U-87MG [51 ] Moraceae Ficuscarica LatexFCL extract 0.125 mg/ml for 24 and 48 h ↓HMGA2, VEGFA ↑HMGA2, VEGFA T98G, U-138 MG, U-87 MG [52 ] Magnoliaceae Magnoliaofficinalis Honokiol 10, 20 µ g/ml for 12 or 24 h ↓STAT3 signaling, ERK1/2, ↑p38 MAPK signaling pathway G0/G1 phase cell cycle arrest U87MG, U251, T98G [53 ] Apocynaceae/Zingiberaceae Rhazyastricta , Zingiberofficinale Crude alkaloid (CAERS), flavonoid (CFEZO) 10 µ g/mL/for 24, 48, 72 h ↓nuclear NF-kB, p65, survivin, XIAP, cyclin-D1, ↑mitochondrial cytochrome c, Bax : Bcl-2 ratio, activities of caspase-3 and -9, and PARP-1 cleavage, p53, p21, Noxa U251 [54 ] Primulaceae Ardisiapusilla A.DCArdipusilloside I 20 µ g/mL for 24 h ↑Beclin 1, LC3 arrest at G2/M phase U373, T98G [55 ] Berberidaceae Berberisamurensis Berbamine derivative, BBMD3 1 µ g/mL/24 h or 48 h ↑miRNA-4284, JNK/AP-1 signaling, caspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP) microRNA-4284 (miR-4284), phosphorylation of the cJun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) Cancer stem-like cells (CSCs) from four GBM patients (PBT003, PBT008, PBT022, and PBT030) [56 ] Solanaceae Withaferin A (WA) 0.025–3 μ M for 72 h ↓G2/M cell cycle arrest, phosphorylation of AKT, mTOR, p70 S6K, c-Met, EGFR, Her2 U87MG, U251, T98G [57 ] Amaryllidaceae Sternbergialutea Lycorine ↓actin, CYP3A4 cytostatic effect B16F10 melanoma (mice) [58 ] Lavandin, peppermint, spearmint, sage, cherries, cranberries, Perilla (Perillafrutescens ), lemongrass, wild bergamot, gingergrass, savin, caraway, celery seeds//lemon Perillyl alcohol (monoterpene alcohol) // Perillyl alcohol: ↑TGF-β Limonene: ↓isoprenylation, coenzyme Q synthesis [59 ] Apiaceae Angelica sinensis Methanol extract of Angelicasinensis 100 µ L for 72 h ↑p16 and p53, CDK inhibitors cell cycle arrest at the G0-G1 phase DBTRG-05MG, BALB/3T3 [20 ] 4,6-Dichloro-5-aminopyrimidine Thiazolo 5,4-d pyrimidines 48 h T98G [60 ] Apiaceae Bupleurum scorzonerifolium (Nan-Chai-Hu) Isochaihulactone No concentration (all cell ER stress Western) 80 μ M for 0, 24, 48 h (cell cycle) 20, 40, 80 μ M for 24 h (Annexin V-PI double stain) 50, 200 mg/kg daily for 30 d (in vivo) ↑DDIT3, NAG-1, PARP, caspase-3/9/7 ↓pERK, Bcl-2 cell cycle arrest G2/M phase, subG1 population increase (naturally pERK induce DDIT3. But DDIT3 increased with low pERK. There is new pathway to increase DDIT3) GBM cell lines 8401, 8901, U87MG, G2T, 131TXM, 1XM, RG2, GL261 (each cell for ER stress Western, 2 cells for cell cycle) [61 ] Solanaceae Lycium chinense (Lycii radicis [Cortex]) Kukoamine A 0, 5, 10, 20 μ M for 48 h (cell cycle) 40, 60, 80 μ M for 48 h on U251; 10, 20, 30 μ M for 48 h on WJ1 (Annexin V-PI double stain, cell activation observed, Western) ↑Bax, caspase-3, E-cadherin ↓5-Lipoxygenase (5-LOX), Bcl-2, CCAAT/enhancer binding protein β (C/EBPβ ), N-cadherin, vimentin, twist and snail+slug Proliferation, colony formation, migration, invasion, growth of tumors all decreased, cell cycle arrested G0/G1 phase, less cell cycle S phase, less cytotoxic for C6 Human GBM cells U251 & WJ1, rat glioma cells (C6) [62 ] Valerianaceae Nardostachys jatamansi [Rhizome] N/A 0, 20, 40, 60, 80 µ g/mL for 24, 48, 72 h (cell counting, AO/EB Dual Fluorescence Staining) 0, 20, 40, 60, 80 µ g/mL for 24 h (cell cycle analyses) 0, 20, 40, 60, 80 µ g/mL for 1 week (clonogenic assay) 10–70 µ g/mL for 24 h (DNA Fragmentation) No concentration measured for 24 h (Western immunoblotting) ↓caspase-3/9, PARP cell shrinkage, membrane blebbing, echinoid processes, pyknosis, myorrhexis, low density (~40 µ g/mL) early apoptosis, high density (60 µ g/mL) late apoptosis, G0/G1 arrest 60, 80 µ g/mL U87M (every experiment), U373MG [63 ] N/A N/A Myricetin 200 μ M for continuous time (over 90 h) (real-time cell analyser instrument) 25, 50, 100, 200 μ M for 24 h (Western) ↑Bax, cleaved caspase-3, caspase-9, Bad ↓cytochrome c, Bcl-2, MDM2, K-Ras, Raf-1, ERK, pERK DBTRG-05MG, U251, U87MG (DBTRG-05MG for every experiment, 3 cells for real-time cell viability) [64 ] Lamiaceae Melissa officinalis Rosmarinic acid (RA) // luteolin-7-glucoside, caffeic acid, rosmarinic acid, protocatechuic acid, caftaric acid, ferulic acid, cichoric acid, Dulbecco’s modified Eagle’s medium (DMEM), Ampliflu Red, 2′,7′-Dichlorofluorescin diacetate (DCFH2-DA), 3-(4,5-dimethylthiazol2-yl)-2,5-diphenyl-tetrazolium bromide (MTT), HPLC grade acetonitrile, trifluoroacetic acid (TFA) 0, 50, 100, 140, 170, 200, 250, 300, 400 μ M for 24, 48 h (RA cell viability) 0, 50, 100, 140, 170, 200 μ M for 24, 48 h (N1 cell viability) 0, 10, 25, 40, 50, 75, 100 μ M for 24, 48 h (N2, N3 cell viability) (highest density is 0% survive) ↑intracellular reactive species (RS) (high density) ↓intracellular reactive species (RS) (low density) cell proliferation decrease, at low density cell viability increase, at middle density apoptosis & antioxidant effect, at high density prooxidant effect & necrosis RA < Aqueous < Ethanolic 40% < Ethanolic 70% (effect) (pure RA, aqueous (N1), ethanolic 40% (N2), ethanolic 70% (N3), 4 kinds compared) C6 rat glioblastoma [65 ] N/A N/A β -Escin temozolomide (TMZ)0, 2, 4, 6, 8, 10 μ M for 48 h (cell viability) 0, 2, 4, 6, 8, 10 μ M β -escin + 0, 2, 4, 6, 8, 10, 50, 100 μ M TMZ for 48 h (β -escin, TMZ combined cell viability) No measurement of concentration for 24 h (Western only PARP-1) ↑cleaved PARP-1 synergy with TMZ (Patient-derived) glioblastoma-initiating cells (GIC), U87MG [66 ] Araceae Acori graminei [Rhizoma] N/A 0, 50, 100 μ g/mL for 48 h on A172; 0, 100, 200 μ g/mL for 48 h on U251 (Annexin V-PI double stain) 0, 25, 50, 100 μ g/mL for 48 h on A172; 0, 50, 100, 200 μ g/mL for 48 h on U251 (Western) ↑Bax, cleaved caspase-3/8/9, mTOR (A172 only), LC3II/I, atg5, beclin-1, p-AMPK (both) ↓Bcl-2, p-p70S6K, p-mTOR (A172 only), p62 (both) Etop inhibition pathway is contrasted with each experiments dependent/independent confirm A172, U87MG, U251, U118, 4 cell MTT (all experiments) [67 ] Araliaceae Panax ginseng Ginsenoside Rg3 temozolomide (TMZ) 10, 20, 40, 80, 120, 180 μ g/mL TMZ or RG3 for 24, 48, 72, 96, 120, 144 h; 10, 80, 180 μ g/mL TMZ&RG3 1 : 1 for 24, 48, 72, 96, 120, 144 h (proliferation inhibition) ↓VEGF Synergy with TMZ Primary human umbilical vein endothelial cells (HUVECs), rat C6 glioma cell [68 ] Lamiaceae Zataria multiflora Thymol, carvacrol 0, 25, 50, 100, 150, 200 μ g/ml for 2 h and 0, 3, 6 Gy Ionizing radiation (IR). After IR incubated for 48 h in fresh medium (MTT) ZM treatment strengthen IR antiproliferation A172 [69 ] Boraginaceae Lithospermum Shikonin 2.5, 5, 7.5 μ mol/L for 0, 12, 24, 36, 48, 72 h (Cell proliferation) 0, 2.5, 5, and 7.5 μ mol/L for 0, 24, 48 h (scratch wound-healing assays) 2.5, 5, 7.5 μ mol/L for 48 h (Western) ↑p-β -catenin Y333 (U251 only) ↓MMP-2, MMP-9, p-AKT, p-PI3K (both), p-β -catenin Y333 (U87 only) scratch wound-healing assay: higher density shikonin less regrowth U87MG, U251 [70 ] Zingiberaceae Curcuma longa Curcumin (diferuloylmethane) temozolomide (TMZ) 20, 50, 100 μ M curcumin for 72 h 100, 300, 500 μ M TMZ for 72 h (MTT) ↑N/A ↓N/A Synergy with TMZ U87MG [89 ] Taiwanese propolis (Erhmei (in central Taiwan), Fangliao (in southern Taiwan)) Prenylflavanone (propolin G), Taiwanese propolis (TP) 0, 2.5, 5, 10 µ g/mL/72 h (cell cycle analysis). 7.5 µ g/mL/24 h (morphological analysis of apoptotic cells). 12.5 µ g/mL/0, 4, 5, 6, 7 h (activity of caspase. Rat C6 glioma). 0, 2.5, 5, 7.5, 10 µ g/mL/48 h (Western blotting assay). 2.5, 5, 10, 20, 40 µ M with 1.0 mL of 0.3 mM DPPH in methanol (DPPH free radical scavenging activity) ↑sub-G1 cell population, caspase-3, caspase-8, caspase-9, cleavage form of PARP (85 kDa), p21waf1, ↓ procaspase-3, procaspase-8, procaspase-9, Bid, cyclin B1, cyclin D1, EC50 (20.5 µ M)/caspase-dependent signal pathway, mitochondrial-dependent pathway, modulation of cell cycle regulators’ gene expression, ROS rat C6 glioma, DBTRG-05MG (human) [71 ] Curcumin 20 µ mol/L/12, 24 h (cell cycle analysis). 0, 5, 10, 15, 20, 25 µ mol/L/2 h (Western blot). 20 µ mol/L/0, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 48 h (Western blot). 20 µ mol/L/0, 15, 30, 60, 120 min (Western blot). 20 µ mol/L/0, 5, 15, 30, 60 min (Western blot) ↑G1 phase, p21, Egr-1, phosphorylated ERK1/2, JNK1/2, p38, phosphorylated Elk-1, ↓S phase, G2-M phase, cyclin D1/cell cycle arrest (G1 phase), ERK and JNK MAPK/Elk-1/Egr-1 signal cascade (p53-independent transcriptional activation of p21Waf1/Cip1) U-87MG [47 ] Ranunculaceae Coptischinensis , Hydrastiscanadensis Berberine 50, 75, 100, 150 µ g/ml/48 h (cell cycle analysis). 0, 50, 100, 150, 200 µ g/ml/24 h (Western blot, caspase-3 colorimetric protease assay) ↑G1 phase, p27, Bax, caspase-9, caspase-3, PARP, ↓G2/M phase, S phase, CDK2, CDK4, cyclin D, cyclin E, Bcl-2 family, procaspase-9/cell cycle arrest (G1 phase), apoptosis (disruption of the mitochondrial membrane potential, activation of caspase pathways) T98G [72 ] Hypericum polyanthemum Three benzopyrans (6-isobutyryl-5,7-dimethoxy-2,2-dimethyl-benzopyran (1), 7-hydroxy-6-isobutyryl-5-methoxy-2,2-dimethyl benzopyran (2), 5-hydroxy-6-isobutyryl-7-methoxy-2,2-dimethyl-benzopyran (3)) 10 µ g/ml/96 h (cell cycle analysis) ↑% sub-G1/cell cycle arrest (G2/M phase) U-373MG [74 ]