천연항암제: 한약재의 빛

 

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

https://cmjournal.biomedcentral.com/articles/10.1186/s13020-019-0270-9

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine - Chinese Medicine

Table 1 List of anti-cancer natural compounds from Chinese herbal medicines

From: Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

Compounds            Anti-cancer effects          Underlying mechanisms                Dosage   Combinational agents

Curcumin					Anti-angiogenesis; anti-metastasis; anti-proliferation; induces cell cycle arrest; inhibits cell viability; pro-apoptosis	Activates caspase-3, -9, PARP; Down-regulates Akt, Bcl-2, Bcl-xL, CTGF, cyclin D1, cyclin E1, ERK1/2, EZH2, FoxM1, GLI1, ITGA5, Jak1, JNK, MMP-2, Mcl-1, NF-κB, Notch1, p15, p16, p62, p70S6 K, ROCK1, RhoA, SHH, SSAT, STAT1, STAT3, Suz12, TROP2, vimentin, WT1, XIAP, YAP/TAZ; Enhances cytochrome c release, ROS accumulation; Inhibits CDK2 activity, PI3K/Akt/mTOR, SHH/GLI1, STAT3, TGF-β pathways; Up-regulates AIF, Bax, Bex-1, -2, -3, -4, -6, HIF-1α, microRNA-15a, microRNA-16-1, microRNA-99a, p21, p53, p73, PKD1, SMOX	0–5 μM; 0–15 μM; 0–16 μM; 0–20 μM; 0–25 μM; 0–40 μM; 0–50 μM; 0–125 μM; 10–40 μM; 15, 25 μM; 25 μM; 30 μM; 0–6 μg/ml; 5 mg/kg; 60 mg/kg; 200 mg/kg; 500 mg/kg; 25 μg/mouse	Gemcitabine; NVP-BEZ235; α-Tomatine
EGCG					Anti-angiogenesis; anti-metastasis; anti-proliferation; induces autophagy, cell cycle arrest; inhibits cell viability, epithelial–mesenchymal transition; pro-apoptosis	Activates caspase-3, -7, PARP; Down-regulates ABCG2, Akt, AXL, Bcl-2, Bcl-xL, E-cadherin, β-catenin, CDK2, CDK4, COX-2, CTTN, cyclin B1, cyclin D1, cyclin D2, cyclin D3, DNMT1, EGFR, ERα, ERK1/2, FAK, FN1, GSK3β, HDAC1, HER2, HSP90, IKKα, JNK, MDR-1, MGMT, MMP-2, MMP-9, NANOG, NF-κB, Notch, Oct-4, u-PA, paxillin, P-gp, PI3K, Raf-1, Snail, SOX2, Sp1, Src, STAT3, survivin, TFAP2A, Tyro3, VEGF, vimentin; Enhances cytochrome c release, ROS accumulation; Induces mitochondrial depolarization; Inhibits MAPK/ERK, PI3K/Akt pathways; Reduces ATP levels; Represses DNA replication; Up-regulates Bax, CK1α, endostatin, microRNA-16, p21, p53, TIMP-1, TIMP-2	0–20 µM; 0–40 µM; 0–50 µM; 0–100 µM; 0–200 µM; 0–400 μM; 2–100 μM; 10 μM; 20 μM; 25, 50, 100 μM; 40 μM; 50, 100 μM; 80 µM; 0–60 μg/ml; 10 mg/kg; 10–20 mg/kg; 15 mg/kg; 16.5 mg/kg; 20 mg/kg; 25 mg/kg; 25–100 mg/kg; 50 mg/kg; 0.025%, 0.05%; 0.06%	Bleomycin; Cisplatin; Curcumin; Docetaxel; 5-Fluorouracil; Oxaliplatin; Pterostilbene; Temozolomide	]
Berberine					Anti-angiogenesis; anti-proliferation; anti-metastasis; enhances radiosensitivity; induces autophagy, cell cycle arrest; inhibits cell viability, epithelial–mesenchymal transition; pro-apoptosis	Activates caspase-3, -7, -8, -9, PARP; Decreases mitochondrial membrane potential, catalase and superoxide dismutase activities; Down-regulates Akt, AR, Bcl-2, Bcl-xL, Bid, β-catenin, N-cadherin, CDK1, CDK2, CDK4, COX-2, PLA2, cyclin A1, cyclin B1, cyclin D1, cyclin E, DHCR24, DHFR, E2F1, EBNA1, EGFR, EF-Tu, ERK, Ezrin, FAK, FN, HER2, HIF-1α, HMGB1, HNF4α, ITGβ1, Jak2, JNK, Mcl-1, MEK, MMP-1, MMP-2, MMP-9, mTOR, c-Myc, NANOG, NF-κB, iNOS, occludin, Oct-4, p38, p50, p62, p100, p105, p70S6 K, paxillin, u-PA, PCNA, PDK1, PGE2, PKC-α, PSA, PTEN, PTTG-1, RAD51, b-Raf, c-Raf, Septin-8, Slug, Snail, SOX2, Sp1, Src, STAT3, survivin, UQCRC1, VEGF, vimentin, Wnt5α, ZEBRA; Enhances cytochrome c release, ROS accumulation, SSAT activity; Induces DNA damage; Inhibits Akt/mTOR/p70S6 K/S6, arachidonic acid metabolic, androgen receptor pathways; Reduces NO production; Suppresses Hedgehog signaling pathway; Up-regulates ACC, AIF, AMPKα, Apaf-1, ATF-6, Bad, Bak, Bax, Beclin-1, Bim, E-cadherin, DR5, FasL, FoxO1, FoxO3a, GRP78, HRK, Lig4, MST1, p21, p27, p53, PHLPP2, SSAT, TIMP-2, TRAIL, ULK1	0–10 µM; 0–20 μM; 0–25 μM; 0–40 μM; 0–50 µM; 0–80 μM; 0–90 µM; 0–100 µM; 0–120 µM; 0–150 μM; 0–160 µM; 0–200 µM; 0–250 μM; 0–350 μM; 0–1000 μM; 10–80 μM; 15 µM; 20 μM; 50 μM; 0–1 µg/ml; 0–80 μg/ml; 5 mg/kg; 10 mg/kg; 12.5–50 mg/kg; 20 mg/kg; 50, 100 mg/kg; 50–200 mg/kg; 200 mg/kg; 0.01136 g/kg	Caffeine; Cetuximab; Doxorubicin; Erlotinib; d-limonene; Niraparib; Tamoxifen; Taxol; TRAIL
Artemisinins					Anti-metastasis; anti-proliferation; induces apoptosis, autophagy, cell cycle arrest; inhibits cell viability	Activates caspase-3, -8, -9, PARP; Decreases mitochondrial membrane potential, MMP activity; Down-regulates Bcl-2, CDK2, CDK4, cyclin D1, cyclin E2, Dvl2, ERK1/2, LRP6, MMP-2, NANOG, Oct-4, p38, p62, SOX2, vimentin, Wnt5α/β; Enhances cytochrome c release, ROS accumulation; Induces DNA damage; Inhibits Wnt/β-catenin signaling pathway; Up-regulates Axin2, Bax, E-cadherin, β-catenin, NKD2, p16, TIMP-2	0–75 μM; 0–160 μM; 0–200 μM; 0–250 μM; 0–400 μM; 0–500 μM; 0–1000 μM; 0–1200 μM; 10–320 μM; 40–160 μM; 0–40 μg/ml; 10 mg/kg; 50 mg/kg; 60 mg/kg; 100 mg/kg	3CA; Halofuginone; Holotransferrin; Resveratrol
Ginsenoside Rg3					Anti-angiogenesis; anti-proliferation; anti-metastasis; enhances radiosensitivity; increases cell survival; induces autophagy, cell cycle arrest; inhibits chemotaxis, epithelial–mesenchymal transition; pro-apoptosis	Activates caspase-3, -8, -9, 12, PARP; Decreases mitochondrial membrane potential; Down-regulates Akt, AQP1, B7-H1, B7-H3, Bcl-2, Bcl-xL, VE-cadherin, CDK2, COX-2, CXCR4, cyclin D1, cyclin E, DNMT3A, EGFR, EPHA2, ERK, FUT4, HDAC3, HIF-1α, HK2, IAP, JNK, LeY, MMP-2, MMP-9, mTOR, c-Myc, NF-κB, p38, p53, PCNA, PD-L1, PI3K, PKM2, Rb, STAT3, surviving, VEGF; Enhances cytochrome c release, ROS production; Inhibits the Warburg effect, Wnt/β-catenin pathway; Up-regulates Atg-5, Atg-7, Bax, CHOP, IRE1, microRNA-532-3p, p16, p21, p27, p53, PERK	0–10 μM; 0–30 μM; 0–35 μM; 0–60 μM; 0–80 μM; 0–100 μM; 0–150 μM; 0–160 μM; 0–200 μM; 0–400 μM; 0–600 μM; 25 μM; 0–600 ng/ml; 0–80 μg/ml; 0–100 μg/ml; 0–160 μg/ml; 0–200 μg/ml; 40, 80 μg/ml; 50 μg/ml; 80, 160 μg/ml; 80, 160 mg/ml; 3 mg/kg; 5 mg/kg; 5, 10, 20 mg/kg; 6 mg/kg; 7.5–30 mg/kg; 10 mg/kg; 20 mg/kg	Cisplatin; Cyclophosphamide; Erlotinib; 5-Fluorouracil; Oxaliplatin; Paclitaxel	,
Ursolic acid					Anti-angiogenesis; anti-metastasis; anti-proliferation; enhances chemosensitivity; induces apoptosis, autophagy, cell cycle arrest; inhibits MDR	Activates caspase-3, -7, -8, -9, Fas receptor, PARP; Decreases mitochrondrial membrane potential; Down-regulates AEG-1, Akt, Bcl-2, Bcl-xL, Bid, β-catenin, CD31, cyclin D1, EGFR, ERK, cFLIP, FN, HIF-1α, cIAP-1, ICAM-1, IκBα, IKKα/β, IL-8, Jak2, Ki-67, Mcl-1, MMP-2, MMP-9, NF-κB, iNOS, p65, u-PA, P-gp, S6 K, Src, STAT3, survivin, mTOR, TNF-α, VEGF, Wnt5α/β, XIAP; Enhances cytochrome c release, PGE2 levels, ROS production; Inhibits NO production; Up-regulates ACC, AMPK, ASK1, Bax, CHOP, DR4, DR5, eIF2α, GRP78, GSK3β, IL-12, JNK, c-Jun, NADPH, p21, p52, p53, PERK	0–4 μM; 0–16 μM; 0–17.5 μM; 0–20 μM; 0–40 μM; 0–50 μM; 0–80 μM; 0–100 μM; 4 μM; 20 μM; 0–400 μg/ml; 10 mg/kg; 25–100 mg/kg; 50 mg/kg; 75 mg/kg; 250 mg/kg; 2 μmol/mouse	Capecitabine; 5-Fluorouracil; Oxaliplatin; Resveratrol; TRAIL
Silibinin					Anti-metastasis; anti-proliferation; induces apoptosis, autophagy, cell cycle arrest; inhibits cell viability	Activates caspase-3, -8, -9, PARP; Down-regulates Akt, Bcl-2, EGFR, ERK, GLI1, IL-1β, FN, MMP-2, MMP-7, MMP-9, NF-κB, iNOS, PLA2, TNF-α, mTOR; Enhances CYP2E1 activity, cytochrome c release, ROS production; Up-regulates AIF, Bax, Bid, calpain, EGR1, ICAD, NAG-1, PTEN	0–75 μM; 0–100 μM; 0–200 μM; 0–300 μM; 0–800 μM; 25, 50 μM; 120 μM; 125 μM; 200 mg/kg; 300 mg/kg; 0.5%	Curcumin; luteolin
Emodin					Anti-metastasis; anti-proliferation; induces apoptosis, autophagy, cell cycle arrest; inhibits cell viability, epithelial-mesenchymal transition	Activates caspase-3, -9, PARP, chloride currents; Decreases mitochondrial membrane potential; Down-regulates Akt, Bcl-2, Bcl-xL, Bim-1, β-catenin, CDK1, CSF1, CSF2, CXCL12, CXCR4, cyclin D1, ERα, ERK, FABP4, bFGF, HBP17, HER2, ILK, Jagged1, Jak1, Jak2, Ki-67, Mcl-1, MCP-1, MMP-2, MMP-9, MRP1, NF-κB, p38, p62, u-PA, u-PAR, Slug, Snail, Src, STAT3, survivin, Thy-1, VEGF, vimentin, XIAP, ZEB1; Enhances Ca2+ levels, cytochrome c release, ROS production; Up-regulates AIF, Bax, Beclin-1, E-cadherin, GSK3β, microRNA-34, Notch1, SHP-1	0–10 μM; 0–40 μM; 0–50 μM; 0–60 μM; 0–80 μM; 0–100 μM; 0–250 μM; 0–320 μM; 0–1000 μM; 20 μM; 20–80 μM; 40 μM; 0.05 mM; 40 mg/ml; 20, 40 mg/kg; 20, 50 mg/kg; 25, 50 mg/kg; 40 mg/kg; 50 mg/kg	Cisplatin; curcumin; 5-fluorouracil; gemcitabine
Triptolide					Anti-angiogenesis; anti-metastasis; anti-proliferation; enhances radiosensitivity; induces autophagy, cell cycle arrest; inhibits cell viability; pro-apoptosis	Activates caspase-3, -7, -8, -9, GSK3β, PARP; Decreases mitochondrial membrane potential; Down-regulates Akt, AR, BCAR1, Bcl-2, β-catenin, Cav-1, CD147, CDK2, CHK1, COX IV, CXCR4, cyclin A1, ERK, ETS2, FAK, c-FLIP, GRB2, HIF-1α, HSF1, HSP70, IκBα, ITGβ1, ITGαVβ6, JMJD3, JMJD2B, NK, p38 MAPK, Mcl-1, MKP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-14, MMP-19, c–Myc, NF-κB, iNOS, Nrf2, p65, PCNA, PI3K, PYK2, ROCK1, RhoA, Slug, Snail, SOS1, Src, survivin, mTOR, Twist, UTX, VEGF, vimentin, ZEB1; Enhances Ca2+ levels, cytochrome c release, ROS production; Inhibits Wnt/β-Catenin pathway; Up-regulates ATM, Bax, Beclin-1, E-cadherin, cathepsin B, Fas, DKK1, DR5, ENY2, FADD, FRZB, GSK3β, IL-2, γ-H2AX, LMP, LSD1, p53, PPARγ, PTEN, SFRP1, SIRT3, Smac, SUV39H1, TNF-α, Wnt3α	0–10 nM; 0–40 nM; 0–50 nM; 0–80 nM; 0–100 nM; 0–160 nM; 0–200 nM; 0–300 nM; 0–320 nM; 0–400 nM; 0–500 nM; 0–0.1 μM; 0–25 μM; 0–150 μM; 0–200 μM; 10 nM; 50, 72 nM; 100 nM; 0–8 ng/ml; 0–36 ng/ml; 0–50 ng/ml; 0–400 ng/ml; 5, 10 ng/ml; 5–160 ng/ml; 8 ng/ml; 250 μg/kg; 0–0.8 mg/kg; 0.04–0.36 mg/kg; 0.075 mg/kg; 0.15 mg/kg; 0.25 mg/kg; 0.4 mg/kg; 1 mg/kg; 1.5 mg/kg; 2–4 μg/mouse	Cisplatin; epirubicin; 5-fluorouracil; gemcitabine; hydroxycamptothecin
Cucurbitacin B					Anti-angiogenesis; Anti-metastasis; Anti-proliferation; Inducing apoptosis, cell cycle arrest; Inhibits epithelial-mesenchymal transition	Activates caspase-3, -8, -9, PARP; Decreases mitochondrial membrane potential; Down-regulates Akt, ACLY, BCAR1, Bcl-2, β-catenin, CD31, CDK1, CIP2A, cyclin B1, cyclin D1, EGFR, ERK, FAK, galectin-3, GSK3β, HER2, HIF-1α, ILK1, ITGA6, ITGB4, Jak2, MMP-2, MMP-9, MRP1, c-Myc, nucleophosmin, P-gp, paxillin, RhoA, ROCK1, STAT3, Src, survivin, TACE, TCF1, mTOR, Twist, VEGF, VEGFR2, Wnt3; Enhances cytochrome c release, PP2A activity, ROS production; Inhibits Wnt/β-catenin pathway; Up-regulates ATM, Bax, Bim, E-cadherin, CDC25C, CHK1, γ-H2AX, JNK, p21, p53	0–100 nM; 0–200 nM; 0–1000 nM; 0.1–1000 nM; 0–0.1 μM; 0–1 μM; 0–1.6 μM; 0–30 μM; 0–100 μM; 0–128 μM; 0.02– 62.5 μM; 0–100 μg/ml; 0.1–100 μg/ml; 0.1, 0.2 mg/kg; 0.1, 0.25 mg/kg; 0.5, 1 mg/kg; 1, 5 mg/kg; 2 mg/kg; 10 mg/kg; 0.1 μmol/mouse	Curcumin; docetaxel; gefitinib; gemcitabine
Tanshinone IIA					Anti-angiogenesis; anti-metastasis; anti-proliferation; enhances chemosensitivity, radiosensitivity; induces autophagy, cell cycle arrest; inhibits cell viability, epithelial–mesenchymal transition; pro-apoptosis	Activates caspase-3, -8, -9, -12, PARP; Down-regulates ALDH1, Bcl-2, BIP, N-cadherin, β-catenin, CD31, COX-2, CTGF, FoxM1, HIF-1α, Ki-67, LEF1, MCP-1, Mfn-1, Mfn-2, MMP-2, MMP-9, c-Myc, NANOG, Opa-1, p65, PCNA, Slug, Snail, STAT3, survivin, TCF3, VEGF, vimentin, YAP; Enhances cytochrome c release, ROS accumulation; Reduces mitochondrial membrane potential; Up-regulates ATF-4, Bax, Bak, Bad, E-cadherin, CHOP, Drp-1, DR5, GRP78, p21	0–8 μM; 0–20 µM; 0–40 µM; 0–60 µM; 0–80 μM; 0–100 µM; 0–54.4 μM; 0–20 ng/ml; 0–4 µg/ml; 0–8 μg/ml; 0–18 µg/ml; 0–60 µg/ml; 1 mg/kg; 10, 30 mg/kg; 20 mg/kg	Adriamycin 5-fluorouracil; TRAIL
Oridonin					Anti-angiogenesis; anti-metastasis; anti-proliferation; induces apoptosis, autophagy, cell cycle arrest, epithelial–mesenchymal transition	Activates caspase-3, -8, -9, PARP; Decreases mitochondrial membrane potential; Down-regulates Akt, AMPK, AP-1, Bcl-2, Bcl-xL, N-cadherin, CD31, CD44, CDC25C, CDK1, CDK2, Claudin 1, Claudin 4, Claudin 7, α-CPI, cyclin B1, cyclin D1, cyclin E, DHFR, EGFR, ERK, GLUT-1, GSK3β, HO-1, ICAD, Mcl-1, MCT1, MDM2, MMP-2, MMP-9, c-Myc, NF-κB, Notch, Nrf2, NQO1, p38, p62, PCNA, PI3K, Rac2, Raf, Ras, SERTAD1, Slug, Smad, Snail, Stathmin, SREBP1, mTOR, vimentin; Enhances cytochrome c release, intracellular Ca2+ levels, ROS production; Inhibits TrxR activity; Up-regulates AIF, ASK1, ATM, Bad, Bax, Beclin-1, Bim, BMP7, E-cadherin, CHK2, CHOP, CKS2, eIF2α, FADD, GADD45AQ, GRP78, γ-H2AX, HERC5, HSP90, IRE1, JNK, p21, p53, PERK, PPARγ, RECQL4, SFN, PTEN	0–1000 nM; 0–1.5 μM; 0–4 μM; 0–9 μM; 0–12 μM; 0–15 μM; 0–20 μM; 0–25 μM; 0–30 μM; 0–32 μM; 0–40 μM; 0–50 μM; 0–60 μM; 0–64 μM; 0–80 μM; 0–100 μM; 0–160 μM; 36 μM; 0–10 mM; 0–64 μg/ml; 5–30 μg/ml; 1.875, 7.5 mg/ml; 1 mg/kg; 2–8 mg/kg; 2.5–10 mg/kg; 5, 10 mg/kg; 5–10 mg/kg; 5–15 mg/kg; 7.5–30 mg/kg; 10 mg/kg; 10, 20 mg/kg; 15 mg/kg; 30 mg/kg; 50, 100 mg/kg	Cisplatin; NVP-BEZ235; valproic acid
Shikonin					Anti-metastasis; anti-proliferation; enhances chemosensitivity; induces apoptosis, cell cycle arrest, necroptosis	Activates caspases-3, -8, -9, -12, PARP, JNK/c-Jun, p38 MAPK, PERK/elF2α/CHOP, pathways; Decreases mitochondrial membrane potential; Down-regulates Akt, Bcl-2, CDK4, cyclin D1, FoxO3a, ICBP90, ITGβ1, MDM2, MMP-9, c-Myc, RIPK1; Elevates intracellular Ca2+ and ROS levels; Enhances Ca2+ and K+ efflux; Inhibits ERK pathway, PKM2 activity; Promotes RIP1/RIP3 necrosome formation; Up-regulates Bax, Bim, Cbl-b, CHOP, cytochrome c, EGR1, eIF2α, GRP78, IRE1α, p16, p21, p53, p73, PERK, RIP1, RIP3	0–2 μM; 0–4 μM; 0–5 μM; 0–6 μM; 0–10 μM; 0–20 μM; 0–50 μM; 0.1–0.4 μM; 1 μM; 2 μM; 20 mg/kg; 2 mg/kg	Cisplatin; 5-fluorouracil; oxaliplatin
Gambogic acid					Anti-angiogenesis; anti-metastasis; anti-proliferation; anti-tumor growth; enhances chemosensitivity; induces apoptosis, autophagy, cell cycle arrest; inhibits cell viability, survival	Activates caspase-3, -7, -8, -9, PARP, JNK pathway; Decreases mitochondrial membrane potential; Down-regulates Akt, ALDOA, ATG4B, Bcl-2, Bcl-xL, β-catenin, cFLIPL, cyclin D1, DLL1, DLL3, DLL4, ERK, Jagged1, Jagged2, LRP, p-53, P-gp, Mcl-1, MMP-2, MMP-9, MRP2, PI3K, RRM2, SIRT1, survivin, TOPIIα, VEGF, XIAP; Enhances ROS accumulation, cytochrome c release; Inhibits ERK/E2F1/RRM2, MAPK, PI3K/Akt pathways, NF-κB p65 binding activity, Trx activity; Up-regulates AIF, Atg-5, Bax, CHOP, DUSP1, DUSP5, FoxO3a, c-Jun, p27, p53	200–400 nM; 0–1 μM; 0–2 μM; 0–3 μM; 0–5 μM; 0–8 μM; 0–10 μM; 0–40 μM; 0–50 μM; 0–51.8 μM; 0.5 µM; 0–3 μg/ml; 2 mg/kg; 8 mg/kg	Chlorochalcone; Cisplatin; Doxorubicin; 5–Fluorouracil; Gemcitabine; Nal131; Oxaliplatin; Retinoic acid; TRAIL
Artesunate					Anti-angiogenesis; anti-metastasis; anti-proliferation; anti-tumor growth; induces apoptosis, cell cycle arrest, DNA damage, ferroptosis	Activates caspase-3, -9, p38 MAPK pathway; Decreases metabolic capacity, mitochondrial membrane potential, PGE2 production; Down-regulates Bcl-2, CDC25A, COX-2, cyclin B, cyclin D1, cyclin E2, γ-H2AX, IGF-1R, Keap1, c-Myc, PAX7, RAD51, STAT3, UCA1, xCT; Enhances ROS production; Up-regulates ATF-4, ATM, ATR, Bax, BRCA1, E-cadherin, CHK1, CHK2, CHOP, HO-1, microRNA-16, microRNA-133, microRNA-206, Nrf2, p53	0.1–10 μM; 0–50 μM; 0–100 μM; 0–120 μM; 0–200 μM; 50 μM; 0–50 μg/ml; 0–160 mg/L; 0–200 mg/kg; 50 mg/kg; 50, 150 mg/kg; 100 mg/kg; 200 mg/kg	Cisplatin; Connexin-43; Paclitaxel
Wogonin					Anti-angiogenesis; anti-metastasis; anti-proliferation; anti-tumor growth; induces apoptosis, autophagy, cell cycle arrest, ER stress, mitochondrial dysfunction; reverses drug resistance	Activates caspase-3, -4, -8, -9, -12, PARP, IRE1α-dependent pathway; Decreases mitochondrial membrane potential; Down-regulates Akt, B7H1, Bcl-2, CDK4, CDK6, cyclin D1, cyclin E, EGFR, ERK, HIF-1α, IL-8, IκB, IKKα, Ki-67, MMP-2, MMP-9, c-Myc, PDK1, PI3K, Rac1, RAE-1ε, SGK1, ULK1, VEGF; Enhances calreticulin, HMGB1, cytochrome c release, ROS accumulation; Inhibits 5-LO/BLT2/ERK/IL-8/MMP-9, NF-κB pathways; Up-regulates ASK, Bax, Bid, GRP78, GRP94, IRE1α, JNK, p21, p53, PU.1, PUMA	0–20 μM; 0–40 μM; 0–50 μM; 0–60 μM; 0–80 μM; 0–100 μM; 0–150 μM; 0–200 μM; 40 μM; 50 μM; 0–40 μg/ml; 0–60 mg/kg; 0–80 mg/kg; 8 mg/kg; 20 mg/kg; 60 mg/kg; 12.5 ng/zebrafish	Cisplatin; Paclitaxel; Oxaliplatin; Sorafenib
β-Elemene					Anti-angiogenesis; anti-metastasis; anti-proliferation; anti-tumor growth; enhances radiosensitivity; induces apoptosis, autophagy, cell cycle arrest; reverses chemoresistance	Activates caspase-3, -7, -8, -9, -10; Down-regulates Akt, Bcl-2, β-catenin, CDC25C, CDK1, cyclin B1, cyclin D1, endostatin, ERK, DNMT1, MMP-2, MMP-3, MMP-9, MTA3, c-Myc, STAT3, Sp1, survivin, TCF7, TIMP-1, TIMP-2, VEGF; Enhances ROS accumulation; Induces polarization from M2 to M1 macrophages; Inhibits Wnt/β-catenin pathway; Up-regulates ATF-4, ATF-6, Bad, Bax, BTF, CHK2, CHOP, FoxO3a, IGFBP1, IRE1α, p15, p21, p53, Pak1, PAK1IP1, PERK, TOPIIα	0–25 μM; 0–1000 μM; 67.5–1000 μM; 0–40 μg/ml; 0–50 μg/ml; 0–120 μg/ml; 0–160 μg/ml; 0–200 μg/ml; 0–320 μg/ml; 0–500 μg/ml; 0–800 μg/ml; 0–0.16 mg/ml; 15, 30 μg/ml; 100 mg/ml; 1 mg/kg; 20 mg/kg; 50 mg/kg; 75 mg/kg; 200 mg/kg	Cisplatin; Paclitaxel; Rapamycin
Cepharanthine					Anti-angiogenesis; anti-metastasis; anti-proliferation; anti-tumor growth; induces apoptosis, autophagy, cell cycle arrest; Reverses multi-drug resistance	Activates caspase-3, -9, PARP; Decreases mitochondrial membrane potential; Down-regulates Akt, Bcl-2, Bcl-xL, CDK4, cyclin A, cyclin D, c-FLIP, mTOR, p50, p52, survivin; Enhances cytochrome c release, ROS accumulation; Inhibits lysosomal cathepsin B and cathepsin D maturation, Akt/mTOR, NF-κB, pathways; Up-regulates Atg-7, Bak, Bax, Beclin1, DR5, p38 MAPK, Mcl-1, p21Waf1/Cip1, p53	0–15 μM; 0–20 μM; 0–80 μM; 0–100 μM; 0–120 μM; 2–8 μM; 4, 5 μM; 5–80 mM; 25 mg/kg; 50 mg/kg	Cisplatin; Dacomitinib; Paclitaxel; TRAIL