Table 1.
Potential antineoplastic effects and underlying mechanisms of action of SFN based on in vitro studies.
| Cell Lines Used | Conc. and Duration |
Anticancer Effects | Mechanisms | References |
|---|---|---|---|---|
| Breast cancer | ||||
| MCF-7 | 0.1–100 µM (1–48 h) |
Increased cytotoxicity | Not reported | Tseng et al., 2004 [93] |
| MCF-7 | 5–30 µM (6–24 h) |
Suppressed cell proliferation | ↑G2/M phase arrest; ↑cyclin B1; ↑H1 phosphorylation; ↓tubulin polymerization | Jackson and Singletary, 2004 [94] |
| F3II | 5–30 µM (12–48 h) |
Inhibited cell growth | ↑G2/M phase arrest; ↑cdc2 kinase activity; ↓tubulin polymerization; ↑apoptosis; ↓Bcl-2; ↓PARP; ↑caspase-3-like activity | Jackson and Singletary, 2004 [95] |
| MCF-7 | 2.5–50 µM (20–72 h) |
Inhibited cell proliferation | ↑G2/M phase arrest; ↑microtubule dysfunction; ↑tubulin acetylation; ↓tubulin polymerization | Azarenko et al., 2008 [96] |
| MDA-MB-231, MDA-MB-468 | 5–50 µM (3–24 h) |
Inhibited cell growth and invasion | ↑Apoptosis; ↑USP14; ↑UCHL5; ↑Ub-Prs | Ahmed et al., 2018 [97] |
| MDA-MB-231, MDA-MB-468, BT-474, MCF-7 | 1–25 µM (24, 72 h) |
Decreased cell growth | ↓HDAC5; ↓HDAC5; ↓USF1; ↓USF1; ↓luciferase; ↓LSD1; ↑H3K4me1/2; ↑ AcH3K9; ↓USP28; ↑CTDSPL; ↑GLPR1; ↑CYLD; ↑TFP12; ↑PPP2R1B; ↑ISG15; ↑EGLN3 | Cao et al., 2018 [98] |
| MCF-7, MDA-MB-231 | 5 µM (24–72 h) |
Inhibited cell growth | ↑G2-M phase arrest; ↓CCND1; ↓CDK4; ↓HDAC2; ↓HDAC3; ↓HMT; ↑p53; ↑p21; ↑H3K4Me3 | Royston et al., 2018 [99] |
| MDA-MB-231, MCF-7, T47D, MDA-MB-468 | 5–25 µM (24–72 h) |
Inhibited cell growth | ↑G2-M phase arrest; ↓cyclin B1 (MDA-MB-231 and MCF-7); ↑apoptosis; ↓global HDAC; ↓EGFR; ↓HER-2 | Pledgie-Tracy et al., 2007 [100] |
| MCF-7, MDA-MB-231, SK-BR-3 | 5–20 µM (24 h) |
Induced cytotoxicity | ↑p21; ↑oxidative stress; ↑carbonylation of lamin A/C; ↓lamin B1; ↓nucleolar RRN3; ↑nuclear RRN3; ↓NOP2; ↓WDR12 | Lewinska et al., 2017 [101] |
| MCF-7, MDA-MB-231, SK-BR-3 | 2.5–20 µM (24 h) |
Inhibited cell proliferation | ↑Apoptosis; ↑G2/M phase arrest (MCF-7 and MDA-MB-231); ↑G0/G1 phase arrest (SK-BR-3); ↑p53; ↑p21; ↓CCNA2; ↓CCNB1; ↓CCNB2; ↓CCND3; ↓CCNE1, CCND1; ↓CCND2; ↓CCNH; ↓p-ERK1/2 (MDA-MB-231); ↑ROS; ↑DNA DSBs; ↑DNA SSBs; ↓Akt signaling; ↓ATP; ↓AMPK activation; ↓5-mdC; ↑HDAC5; ↓HDAC6-10; ↓DNMT1; ↓DNMT3B | Lewinska et al., 2017 [102] |
| MCF-7, MDA-MB-231 | 1–100 µM (24–72 h) |
Induced cell death | ↑Apoptosis; ↑S phase cells; ↑G2/M phase cells; ↑p21; ↑p27; ↓cyclin A; ↓cyclin B1; ↓CDC2; ↑caspase-3; ↓Bcl-2; ↑autophagy; ↑LC3-I; ↑LC3-II | Kanematsu et al., 2010 [103] |
| MCF-7, SK-BR-3, MDA-MB-231, MDA-MB-468 | 5–30 µM (24 h) |
Inhibited cell proliferation | ↑Autophagosomal vacuoles; ↓mTOR; ↓S6K1; ↓p-Akt | Pawlik et al., 2013 [104] |
| MDA-MB-231, BT549, MDA-MB-468 | 10, 25 µM (16–72 h) |
Inhibited cell growth | ↑Autophagy; ↓P62; ↑Beclin1; ↑LC3-II; ↓HDAC6; ↑PTEN; ↓Akt | Yang et al., 2018 [105] |
| MDA-MB-231, MDA-MB-436, MDA-MB-468, MDA-MB-453 |
1–60 µM (24–72 h) |
Inhibited cell proliferation | ↑Apoptosis; ↑G2/M phase arrest; ↑Egr1; ↑NQO1; ↑SL7A11; ↑G6PD; ↑GCLM; ↑SCD; ↑ID1; ↑IGFBP3; ↓cyclin B1; ↓Cdc2; ↓p-Cdc2; ↓Cdc25c | Yang et al., 2016 [106] |
| ZR-75-1 | 6.25–25 µM (4–72 h) |
Inhibited cell growth | ↑G1/S phase arrest; ↓CDK2; ↓CDK4; ↓CDK6; ↓CDK2; ↓CDK4; ↓SERTAD1; ↓CCDN2; ↓HDAC3; ↓SERTAD; ↓CCDN2; ↓HDAC3 | Cheng et al., 2019 [107] |
| SH, SHR | 5–20 µM (72 h) |
Decreased cell proliferation | ↑Apoptosis; ↑S-phase arrest (SH cells); ↑S-phase and G2/M-phase arrest (SHR cells); ↓HDAC1; ↑global histone H3 acetylation; ↑DCBLD2; ↓Septin 9 | Li et al., 2016 [108] |
| MCF-7, ZR-75-1 | 2.5–30 µM (24–72 h, 7 days) |
Decreased cell proliferation | ↓ERα; ↓PR; ↑PSMB5 | Ramirez and Singletary, 2009 [109] |
| T47D, MCF-7, BT-474 | 2–50 µM (96 h) |
Decreased cell viability | ↑Apoptosis; ↑PARP cleavage | Pawlik et al., 2016 [110] |
| MCF-7 | 25 µM 24–72 h |
Inhibited cell proliferation | ↑Apoptosis; ↑caspase-7; ↑PARP cleavage; ↓Bcl-2; ↑Bax; ↓ERK1/2 MAPK; ↑p38 MAPK | Jo et al., 2007 [111] |
| MCF-7 | 0.01–75 µM (24 and 48 h) |
Decreased cell viability | ↑Apoptosis; ↓Bcl-2; ↓COX-2 | Hussain et al., 2013 [112] |
| MCF-7, MDA-MB-231 | 5–20 µM (72 h) |
Decreased cell viability | ↑Apoptosis; ↓CYP1A1 protein (all cell lines); ↓CYP19 (MCF-7); ↑CYP19; ↑aromatase (MDA-MB-231); ↑CYP1A2 (MDA-MB-231) | Licznerska et al., 2015 [113] |
| MCF-7, MDA-MB-231 | 10–70 µM (96 h) |
Inhibited cell growth | ↑Apoptosis; ↑p53 (MCF-7); ↓PTEN methylation; ↑RARβ2; ↑p21 | Lubecka-Pietruszewska et al., 2015 [114] |
| MCF-7, MDA-MB-231 | 5–20 µM (3–15 days) |
Inhibited cell proliferation | ↑Apoptosis; ↓hTERT; ↓telomerase activity; demethylation of CpGs of the CTCF binding site; ↑ac-H3; ↑ac-H3K9; ↓tri-me-H3K27; ↓tri-me-H3K9, ↓DNMT1; ↓DNMT3a | Meeran et al., 2010 [115] |
| MCF-7, MDA-MB-231 | 1–20 µM (24 h) |
Inhibited cell proliferation | ↑Apoptosis; ↓HSP70; ↓HSP90; ↓HSF1; ↑p53; ↑p21; ↑AIF; ↑Bax; ↑Bad; ↓Bcl-2; ↑caspase-3; ↑caspase-8; ↑caspase-9 | Sarkar et al., 2012 [116] |
| MCF-7 | 10 µM (45 min, 6 h) |
Inhibited cell growth | ↑Nrf2; ↑NQO1; ↑HMOX1; ↑H3K9Ac:H3 | Lo and Matthews, 2013 [117] |
| MCF-7 | 1–12 µM (4–24 h) |
↑TrxR1 | Wang et al., 2005 [118] | |
| MDA-MB-231, MDA-MB-468, BT-549, BT-474, SKBR3, HS578T | 20–60 µM (16, 24 h) |
Decreased cell proliferation | ↑Nrf2; ↓RON | Thangasamy et al., 2011 [119] |
| MCF-7, MDA-MB-231 | 1–20 µM (24 h) |
Decreased cell viability and migration | ↑CAV1; ↑CAV1; ↑condensed chromatin | Deb et al., 2014 [120] |
| MDA-MB-231-Luc-D3H1, JygMC(A) | 2.5–20 µM (48 h) |
Decreased cell proliferation | ↓Primary tumorspheres; ↓secondary tumorspheres; ↓tertiary tumorspheres; ↓CR1; ↓CR3; ↓GRP78; ↓Alk4 | Castro et al., 2019 [86] |
| Gastrointestinal tract and associated cancers | ||||
| Esophageal cancer | ||||
| OE33, FLO-1 | 1–12.5 µM (0.5–5 h) |
Inhibited cell growth | ↑Apoptosis; ↑G1 phase arrest; ↓HSP90; ↑p21 | Qazi et al., 2010 [121] |
| EC9706, ECa109 | 10–60 µM (3–72 h) |
Inhibited cell proliferation and induced autophagy | ↑Apoptosis; ↑caspase-9; ↑LC3B-II; ↓p62; ↑Nrf2 | Lu et al., 2020 [122] |
| Gastric cancer | ||||
| AGS | 2.0–6.75 µM (3–24 h) |
Decreased cell growth and migration | ↑Apoptosis; ↑ROS; ↑Bax; ↓Bcl-2; ↑cyt c; ↑caspase-8; ↑PARP-1 cleavage; ↑SFE; ↑p-JNK; ↑p-P-38; ↓p-ERK1/2 | Mondal et al., 2016 [123] |
| AGS | 2.5–20 µM (24, 48 h) |
Inhibited cell viability | ↑Apoptosis; ↑G2/M phase arrest; ↑cyclin B1; ↑p53; ↑p21; ↑p-H3; ↑PARP cleavage; ↑p-AMPK; ↓cyt c; ↓MMP | Choi et al., 2018 [124] |
| MGC803, AGS | 2–32 µM (24–48 h) |
Inhibited cell proliferation | ↑Apoptosis; ↑G2/M phase arrest; ↓SMYD2; ↓SMYD3 mRNA; ↓CYR61; ↓MYL9 | Dong et al., 2018 [125] |
| AGS, MKN45 | 31–250 µM (48 h) |
Inhibited cell growth | ↑Apoptosis; ↑CDX1; ↑CDX2 | Kiani et al., 2018 [126] |
| Colon cancer | ||||
| SW620 | 5–100 µM (24–72 h) |
Decreased cell proliferation | ↑Apoptosis; ↑caspase-3; ↑double-strand DNA breaks | Andělová et al., 2007 [127] |
| SW620 | 20 µM (12–48 h) |
Inhibited cell proliferation | ↑Apoptosis; ↑caspase-9; ↑caspase-3; ↑caspase-7; ↑ATM kinase; ↑Chk2 kinase; ↑JNK | Rudolf et al., 2009 [128] |
| SW480 | 1–20 µM (3–48 h) |
Inhibited cell proliferation | ↑Apoptosis; ↑caspase-3; ↑caspase-7; ↑caspase-9; ↑ERK; ↑p53; ↓Bcl-2; ↑Bax/Bcl-2 ratio; ↑ROS; ↑MDA | Lan et al., 2017 [129] |
| HT-29 | 5–30 µM (24–96 h) |
Inhibited cell growth | ↑Apoptosis; ↑G2/M phase arrest; ↑cyclin A; ↑cyclin B1; ↑Bax; ↑PARP cleavage | Gamet-Payrastre et al., 2000 [130] |
| 40-16, 379.2 | 0.4–50 µM (10–72 h) |
Decreased cell growth | ↑Apoptosis; ↑PARP cleavage; ↓Pro-C9; ↓Pro-C7; ↓Bax; ↓Bcl-xL | Pappa et al., 2006 [131] |
| 40-16 | 5, 10 µM (24–72 h) |
Inhibited cell growth | ↑PARP cleavage; ↑subG1 phase arrest | Pappa et al., 2007 [132] |
| HCT-116 | 0.5–100 µM (16–48 h) |
Suppressed cell growth | ↑Apoptosis; ↑histone H2A.X phosphorylation; ↑caspase-9; ↑caspase-3; ↑JNK; ↑Bid; ↑Bax; ↓Bcl-2 | Rudolf and Cervinka, 2011 [133] |
| HCT-116, HT-29, DLD1, KM12, SNU-1040 | 2.5, 5 µM (24–72 h) |
Inhibited cell proliferation | ↑Apoptosis; ↑PARP cleavage; ↑G2/M phase arrest; ↑CDK1; ↑CDC25B; ↑MK2; ↑P38; ↑p-JNK; ↓microtubule polymerization | Byun et al., 2016 [134] |
| HT-29 | 6.25–100 µM (4–36 h) |
Inhibited cell growth | ↑G1 phase arrest; ↓cyclin D1; ↓cyclin A; ↓c-myc; ↑P21; ↑ERK; ↑JNK; ↑p38 | Shen et al., 2006 [135] |
| CT116 | 5–15 µM (72 h) |
Inhibited cell viability | ↑Apoptosis; ↑G2 phase arrest; ↑p-SAPK; ↓c-Myc | Zeng et al., 2011 [136] |
| 40-16 | 0.4–50 µM (3–48 h) |
Inhibited cell proliferation | ↑G2/M phase arrest (6, 12, and 24 h); ↑subG1 phase arrest (48 h); ↓GSH | Pappa et al., 2007 [137] |
| HT-29 | 15 µM (48 h) |
Inhibited cell growth | ↑Apoptosis; ↓p-cdc2; ↑p21; ↑G2/M phase arrest; ↑Rb phosphorylation; ↑Rb protein | Parnaud et al., 2004 [138] |
| WiDr | 2.5–80 µM (16 h) |
Inhibited cell proliferation | ↑Apoptosis; ↑autophagy; ↑LC3-1; ↑LC3-II; ↓Bcl-2 | Nishikawa et al., 2010 [139] |
| DLD-1, HCT116, LoVo | 5–20 µM (24 h) |
Inhibited cell proliferation | ↓SKP2 mRNA; ↓SKP2 protein; ↑p27KIP1; ↑Akt; ↑ERK | Chung et al., 2015 [140] |
| Caco-2 | 1–50 µM (2, 24 h) |
Inhibited cell viability | ↑KLF4; ↑p21; ↓CDX-2; ↓KLF5; ↓AMACR | Traka et al., 2005 [141] |
| HCT-116, HT29 | 15 µM (6 h) |
Inhibition of cell growth and migration | ↑p53; ↓Wnt/β-catenin; ↑Nrf2; ↑NMRAL2P | Johnson et al., 2017 [142] |
| Caco-2 | 5–25 µM (6–36 h) |
Induced autophagy | ↑LC-II; ↑UGT1A1; ↑UGT1A8; ↑UGT1A10 mRNA; ↑Nrf2 | Wang et al., 2014 [143] |
| Caco-2 | 0.5–20 µM (48 h) |
Decreased cell viability | ↑MRP2 | Harris and Jeffery, 2008 [144] |
| HTC-116, HT-29, SW48, SW480 | 15 µM (24 h) |
Decreased cell viability | ↑G2/M phase arrest; ↓HDAC3; ↓HDAC6; ↑p-H2AX; ↑p-ATR; ↑CtIP acetylation | Rajendran et al., 2013 [145] |
| RKO, HCT-116 | 2.5–20 µM (72 h) |
Inhibited cell growth | ↑Apoptosis; ↓miR-21; ↓HDAC mRNA; ↓hTERT mRNA | Martin et al., 2018 [146] |
| HCT-116, SW480 | 0.9–60 µM (24 h) |
Decreased cell proliferation | ↑pH2AX; ↑pRPA32; ↑p300; ↑histone H4 acetylation | Okonkwo et al., 2018 [147] |
| HT-29 | 0.25–10 µM (24 h) |
Inhibited cell growth | ↓TNF-α; ↓IL-1β; ↓IL-6; ↓IFN-γ; ↓IL-1β | Bessler and Djaldetti, 2018 [148] |
| HT-29 | 10–50 µM (24, 48 h) |
Suppressed cell growth and migration | ↑Apoptosis; ↑subG1 phase arrest; ↑caspase-3; ↓COX-2; ↓HIF-1; ↓VEGF; ↓CXCR4; ↓PGE2 | Tafakh et al., 2018 [149] |
| Caco-2 | 5–100 µM (24, 72 h) |
Inhibited cell proliferation | ↑p-ERK1/2; ↑p-Akt; ↑NQO1; ↑UGT1A1; ↓MRP2 | Jakubikova et al., 2005 [150] |
| HCT-116, LoVo, Caco-2, HT-29 | 1–15 µM (72 h) |
Decreased cell growth | ↑Apoptosis; ↑ROS; ↓procaspase-8 | Kim et al., 2010 [151] |
| HCT-116 | 12.5–50 µM (1–24 h) |
Inhibited cell migration | ↓HIF-1α; ↓VEGF; ↓HO-1; ↓GLUT1 | Kim et al., 2015 [152] |
| Hepatocellular cancer | ||||
| HepG2, Hepa1c1c7 | 5–100 µM (24 h) |
Exhibited cell cytotoxicity | ↑ERK2; ↑MAPK pathway | Yu et al., 1999 [153] |
| HepG2 | 100 µM (24 h) |
Reduced cell viability and promoted cell death | ↑Apoptosis; ↑MT-I RNA; ↑MT-II RNA, ↑MT protein expression; ↑Nrf2; ↑p38; ↑JNK/MAPK pathways; ↑caspase-3; ↑PARP cleavage; ↑Bax; ↓Bcl-2; ↓Bcl-xL | Yeh and Yen, 2005 [154] |
| HepG2 | 5–30 µM (48 h) |
Inhibited cell viability and promotes cell death | ↑Apoptosis; ↑caspase-3; ↑Bax; ↓Bcl-2; ↓Bcl-xL; ↓PARP; ↓β-catenin | Park et al., 2007 [155] |
| HepG2 | 20 µM (24 h) |
Reduced cellular proliferation | ↑HO-1; ↑ARE; ↑Nrf2; ↑ERK1/2; ↓Keap1; ↓p38 MAPK; ↓p-MKK3/6 | Keum et al., 2006 [156] |
| Huh-7, SNU-449, NCTC | 20–60 µM (24 h) |
Reduced cell viability and promoted cell cycle arrest | ↑Apoptosis; ↑G2/M phase arrest; ↑caspase-3; ↑caspase-8; ↑caspase-9; ↓PFKFB4; ↓HIF-1α; ↓VEGF | Jeon et al., 2011 [157] |
| HepG2 | 1.25–20 µM (24 h) |
Reduced cellular proliferation, adhesion, migration, and invasion | ↓STAT3; ↓HIF-1α; ↓VEGF | Liu et al., 2017 [158] |
| Hep3B | 5–20 µM (24, 48 h) |
Decreased cell viability and promoted cell death | ↑Apoptosis; ↓telomerase; ↓hTERT; ↓Akt; ↑ROS | Moon et al., 2010 [159] |
| HepG2 | 10–80 µM (48 h) |
Inhibited cell proliferation, migration, and invasion | ↑Apoptosis; ↓TGF-β–induced EMT; ↓Vimentin; ↑E-Cadherin; ↑GO/G1 arrest; ↑ROS | Wu et al., 2016 [160] |
| HepG2 | 80 µM (24–72 h) |
Inhibited cell proliferation and promoted cell death | ↑Apoptosis; ↑Bip/GRP78; ↑XBP-1; ↑caspase-12; ↑Bid; ↑CHOP/GADD153 | Zou et al., 2017 [161] |
| Hepa 1c1c7, HepG2 | 1–40 µM (24 h) |
Reduced cell viability | ↑CYP1A1; ↑AhR transformation; ↑AhR binding to XRE | Anwar-Mohamed and El-Kadi, 2009 [162] |
| Pancreatic cancer | ||||
| MIA PaCa-2, PANC-1 | 5–40 µM (24–72 h) |
Promoted cell cycle arrest and death | ↑Apoptosis; ↑caspase-3, ↑caspase-8, ↑G2-M arrest, ↑ROS | Pham et al., 2004 [163] |
| AsPC-1, BxPc-3, MIA PaCa-2, PANC-1 | 0.1–100 µM (12–48 h) | Inhibited cell proliferation and promoted cell death | ↑Apoptosis; ↓Akt; ↓Cdk4; ↓p53; ↑proteasomal degradation of HSP90 client proteins; ↑caspase-3; ↓HSP90-p50Cdc37 complex | Li et al., 2012 [164] |
| AsPC-1, BxPc-3, Capan-1, MIA PaCa2 | 10 µM (24, 48 h) |
Reduced cell viability | ↑Apoptosis; ↓NF-κB binding | Kallifatidis et al., 2009 [165] |
| ASPC, PANC-1, and human pancreatic CSCs | 5–20 µM (1–7 days) |
Reduced cellular proliferation and promoted cell death | ↑Apoptosis; ↓Bcl-2, ↑caspase-3; ↓Nanog; ↓Oct-4; ↓PDGFα; ↓Smo; ↓Gli1; ↓Gli2 | Rodova et al., 2012 [166] |
| AsPC-1, BxPc-3, PANC-1, MIA PaCa-2 | 10 nM (24 h) |
Promoted cell death | ↑Apoptosis; ↑miR-365a-3p | Yin et al., 2019 [167] |
| AsPC-1, BxPc-3, PANC-1 | 10 µM (24 h) |
Promoted cell death | ↑miR-135b-5p; ↑RASAL2 | Yin et al., 2019 [168] |
| PANC-1, MIA PaCa-2 | 1–100 µM (24–72 h) |
Inhibited cellular proliferation, invasion, and migration | ↑Apoptosis; ↑ROS; ↑AMPK; ↑E-Cadherin; ↓N-Cadherin; ↓Vimentin; ↑Nrf2; ↑HO-1 | Chen et al., 2018 [169] |
| BxPc-3, AsPC-1 | 10 µM (24 h) |
Reduced cell viability | ↑E-Cadherin; ↑GJIC; ↑Cx43; ↓c-Met; ↓CD133 | Forster et al., 2014 [170] |
| PANC-1 | 10 µM (24 h) |
Exhibited cytotoxicity | ↑Cx43; ↑GJA1 mRNA; ↑GJIC; ↓miR30a-3p | Georgikou et al., 2020 [171] |
| Gynecological cancers | ||||
| Cervical cancer | ||||
| HeLa | 5–30 µM (48 h) |
Decreased cell viability | ↑Apoptosis; ↑sub-G1 phase arrest; ↑Bax; ↓Bcl-2; ↓Bcl-xL; ↓pro-caspase-3; ↓PARP; ↓β-catenin | Park et al., 2007 [156] |
| HeLa | 0.01–100 µM (24 h) |
Inhibited cell growth | ↑Apoptosis; ↑caspase-3; ↓Bcl-2; ↓COX-2; ↓IL-1β | Sharma et al., 2011 [172] |
| HeLa | 2.5 µM (24–72 h) |
Inhibited cell growth | ↓DNMT; ↓DNMT3B; ↓HDAC1; ↑RARβ; ↑CDH1; ↑DAPK1; ↑GSTP1 | Khan et al., 2015 [173] |
| HeLa | 6.25–25 µM (24, 72 h) |
Decreased cell proliferation | ↑G2/M phase arrest; ↑MPM-2; ↓cyclin B1; ↓cyclin B1/CDC2 complex; ↑CDC25C/p-CDC25C ratio; ↑GADD45β | Cheng et al., 2016 [174] |
| Endometrial cancer | ||||
| MFE280, KLE, Ishikawa, Hec1B, Hec1A, MFE296, AN3CA | 1–32 µM (24–72 h) |
Inhibited cell viability | ↑Apoptosis; ↑G2/M phase arrest; ↓ATP; ↑p21; ↑p27; ↑Cdc2 phosphorylation, ↑caspase-3; ↑Bax; ↓Bcl-2; ↓Cox IV; ↓MEK; ↓ERK | Rai et al., 2020 [175] |
| Ovarian cancer | ||||
| SKOV3 | 10–100 µM (12, 24 h) |
Inhibited cell growth | ↑Apoptosis; ↓Akt; ↓p-Akt; ↓PI3K; ↓cyclin D1; ↓cdk4; ↓cdk6 | Chaudhuri et al., 2007 [176] |
| OVCAR3, SKOV3 | 2–50 µM (24–72 h) |
Reduced cell proliferation | ↑Apoptosis; ↑G1 phase arrest | Chuang et al., 2007 [177] |
| MDAH 2274, SKOV3 | 5–20 µM (12–72 h) |
Induced growth arrest and inhibited cell migration | ↑Apoptosis; ↑G1 phase arrest; ↓RB; ↓p130; ↑p107; ↓E2F-1; ↓E2F-2; ↓E2F-3; ↓G1 phase; ↓cyclins; ↓CDKs; ↑non-phosphorylated RB; ↓E2F-1 | Bryant et al., 2010 [178] |
| OVCAR3, OVCAR4, OVCAR5, SKOV3 | 100 µM (72 h) |
Inhibited cell proliferation | ↑p38; ↑ERK; ↑JNK (OVCAR3 and SKOV3); ↑thioredoxin reductase (OVCAR3) | Kim et al., 2017 [179] |
| A2780, SKOV3 | 2–200 µM (6, 24 h) |
Decreased cell growth | ↑Apoptosis; ↑HSP27; ↑JNK; ↑MEK1; ↑p38; ↑p90rsk phosphorylation; ↑IP3R2; ↑NFR2; ↑CHOP; ↑ATF4; ↑GCLC; ↑HMOX1; ↑NQO-1 | Hudecova et al., 2016 [180] |
| PA-1 | 6.25, 12.5 µM (24, 72 h) |
Inhibited cell proliferation | ↑G2/M phase arrest; ↓CDC2; ↓cyclin B1/CDC2 complex | Chang et al., 2013 [181] |
| Hematological cancers | ||||
| Leukemia | ||||
| Jurkat T | 3–30 µM (24–72 h) |
Decreased cell proliferation | ↑Apoptosis; ↑G2/M phase arrest | Fimognari et al., 2002 [182] |
| Jurkat T | 3–30 µM (24, 48 h) |
Reduced cell viability | ↑Apoptosis; ↑G2/M phase arrest; ↑p53; ↑Bax; ↓cyclin D3; ↓CDK4; ↓CDK6 | Fimognari et al., 2003 [183] |
| HL60 | 10–110 µM (24–72 h) |
Inhibited cell viability | ↑Apoptosis | Fimognari et al., 2008 [184] |
| U937 | 1–5 µM (48 h) |
Reduced cell growth | ↑Apoptosis; ↑sub-G1 phase arrest; ↑Bax; ↓Bcl-2; ↑caspase-3; ↑PARP cleavage; ↑ROS; ↑MMP | Choi et al., 2008 [185] |
| U937, HL60, NB-4, KG-1 | 15–60 µM (24, 48 h) |
Decreased cell proliferation | ↑Apoptosis; ↓miR-155 | Koolivand et al., 2018 [186] |
| HL60 | 6–10 µM (10–48 h) |
Decreased cell viability | ↑G2/M phase arrest; ↑ROS ↑intracellular Ca2+; ↑caspase-3; ↑caspase-8; ↑caspase-9; ↑Bax; ↑Bid; ↑Fas; ↑Fas-L; ↑Endo G; ↑AIF; ↑cyt c; ↓Bcl-xL; ↑FADD | Shang et al., 2016 [187] |
| HL60 | 1–25 µM (24, 48 h) |
Inhibited cell viability | ↑Apoptosis; ↑NQO1; ↓NQO1; ↓Keap1; ↑Nrf2; ↓PARP; ↓pro-caspase-2; ↓pro-caspase-3; ↓p50; ↑Bax; ↓Bcl-2; ↓NF-κB | Wu et al., 2016 [188] |
| Nalm-6, REH, RS4 | 2–40 µM (24, 48 h) |
Reduced cell growth | ↑Caspase-3; ↑caspase-8; ↑caspase-9; ↑PARP cleavage; ↑G2/M phase; ↑S phase arrest; ↑p21; ↑cyclin B1; ↓Akt; ↓p-mTOR | Suppipat et al., 2012 [189] |
| B1647 | 10, 30 µM (24 h) |
Inhibited cell proliferation | ↓AQP8; ↓ROS; ↑Nox4 | Prata et al., 2018 [190] |
| L-1210 | 1–5 µM (24, 48 h) |
Induced cell growth arrest | ↑Apoptosis; ↑DNA strand breaks; ↑PS externalization | Misiewicz et al., 2003 [191] |
| Lymphoma | ||||
| B-lymphoma cells | 1–10 µM (24 h) |
Inhibited cell growth | ↑Caspase-3; ↑caspase-7; ↑caspase- 9; ↑PARP cleavage; ↓p38 MAPK; ↓Akt | Ishiura et al., 2019 [192] |
| Lung cancer | ||||
| A549 | 1–100 µM (24 h) |
Induced mitotic arrest and promoted cell death | ↑Apoptosis; ↑G1/S arrest; ↑G2/M arrest; ↓tubulin polymerization; ↑ROS; ↓GSH | Mi and Chung, 2008 [193] |
| LTEP-A2 | 6.25–50 µM (3–72 h) |
Inhibited cellular proliferation | ↑Apoptosis; ↑G2/M arrest | Liang et al., 2008 [194] |
| A549 | 30–90 µM (24 h) |
Decreased cell proliferation | ↑G2/M phase; ↓G0/S phase; ↑p21; ↓cyclin D1 | Zuryn et al., 2016 [195] |
| H1299 | 5–15 µM (24, 48 h) |
Promoted cell cycle arrest and decreased cell viability | ↑Apoptosis; ↑necrosis; ↑G2/M phase; ↓G0/S phase; ↓cyclin B1; ↑cyclin D1; ↑cyclin K | Zuryn et al., 2019 [196] |
| A549, H1299 | 5–15 µM (48 h) |
Promoted cell cycle arrest and cell death | ↑Apoptosis; ↑H3 acetylation; ↑H4 acetylation; ↑p53; ↑p21; ↑Bax; ↑G0/G1 arrest; ↑G2/M arrest; ↓HDAC | Jiang et al., 2016 [197] |
| A549 | 2.5, 5 µM (5 days) |
Decreased cell viability | ↑H3K4me1; ↓miR-9-3; ↓DNMT3a; ↓HDAC1; ↓HDAC3; ↓HDAC6; ↓CDH1; ↓CpG methylation | Gao et al., 2018 [198] |
| A549, H1299 | 1–15 µM (7 days) |
Inhibited cell proliferation and the formation of tumorspheres | ↑Apoptosis; ↓miR-19a; ↓miR-19b; ↓Wnt/β-catenin pathway; ↑Bax; ↑caspase-3; ↑caspase-8; ↑caspase-9; ↓CD133; ↓CD44; ↓ALDH1A1; ↓nanog; ↓oct4; ↓PCNA; ↓cyclin D1 | Zhu et al., 2017 [199] |
| H1299, 95C, 95D | 0.5–100 µM (24, 48 h) |
Inhibited cell proliferation, migration, and invasion | ↓miRNA-616-5p; ↓β-catenin; ↓N-cadherin; ↓vimentin | Wang et al., 2017 [200] |
| A549, CL1-5 | 10–40 µM (72 h) |
Reduced cell viability and aggregation | ↑Apoptosis; ↑chromatin condensation; ↑anoikis, ↑annexin V binding; ↑PS externalization; ↑p53; ↑p21; ↑Bad; ↑Bax; ↑cleaved PARP, ↓procaspase-3; ↓procaspase-7; ↓procaspase-9; ↓p-FAK; ↓p-Akt; ↓β-catenin | Tsai et al., 2019 [201] |
| XWLC-05 | 0.5–5 µg/L (24, 48, 72 h) |
Promoted cell cycle arrest and death | ↑Apoptosis; ↑G2/M phase; ↓G0/S phase; ↑p73; ↑PUMA; ↑Bax; ↑caspase-9; ↓Bcl-2; ↓p53 | Zhou et al., 2017 [202] |
| Cadmium-transformed BEAS-2BR |
2.5, 5, 10 µM (24 h) |
Exhibited cytotoxicity | ↑Apoptosis; ↓apoptosis resistance; ↑autophagy; ↑caspase-3; ↑C-PARP; ↓constitutive Nrf2; ↓Bcl-2 | Wang et al., 2018 [203] |
| PC9/gef, H1975, A549, CL1-5, H3255 | 5–20 µM (48 h) |
Reduced cell proliferation | ↓pEGFR; ↓p-Akt; ↓p-STAT3; ↑proteasome activity | Chen et al., 2015 [204] |
| A549, H1299 | 0.5–5 µM (72 h) |
Reduces cellular proliferation, migration, and invasion | ↑ERK5; ↑p-ERK5 ↑E-Cadherin; ↑ZO-1; ↓pc-jun; ↓pc-Fos; ↓N-Cadherin; ↓Snail1; ↓MMP-2 | Chen et al., 2019 [205] |
| SK-1, A549 | 5–30 µM (24 h) |
Decreased cell viability and promoted cell death | ↑Apoptosis; ↑ERK1/2; ↑Bax; ↑caspase-3; ↑26S proteasome activity; ↓Bim | Geng et al., 2017 [206] |
| HBE exposed to 2% TS and A549 | 1–40 µM (1–7 days) |
Inhibited TS-induced, CSC-like properties | ↓CD133; ↓ALDH1A1; ↓Oct4; ↓Nanog; ↓IL-6; ↓NICD; ↓Hes1; ↓ΔNp63α | Xie et al., 2019 [207] |
| Neurological cancer | ||||
| T98G and U87MG | 20, 40 µM (24, 48 h) |
Decreased cell viability and promoted cell death | ↑Apoptosis; ↑intracellular Ca+2; ↑Bax:Bcl2; ↑caspase-3; ↑caspase-9; ↑caspase-12; ↑cyt. c; ↑calpain; ↑α-spectrin degradation; ↑ICAD cleavage; ↑AIF; ↑Smac; ↑Diablo; ↓IAPs; ↓NF-κB | Karmakar et al., 2006 [208] |
| U87, U373, U118, SF767 | 5–50 µM (24, 48 h) |
Inhibited cell survival and promoted cell death | ↑Apoptosis; ↑ROS; ↑DNA double-strand breaks; ↑γ-H2AX ↑caspase-3; ↑caspase-7; ↑caspase-9 | Bijangi-Visheshsaraei et al., 2017 [209] |
| U87 and U251 | 1–50 µM (24, 48 h) |
Reduced cell viability and promoted cell death | ↑Apoptosis; ↑caspase-3; ↑Bax; ↑ROS; ↓Bcl-2; ↓p-STAT3 | Miao et al., 2017 [210] |
| U251MG | 10–40 µM (24 h) |
Reduced cell viability and invasion | ↑Apoptosis; ↑Bad; ↑Bax; ↑cyt. c; ↑Annexin V-binding capacity; ↓Bcl-2; ↓survivin; ↓invasion; ↓MMP-2; ↓MMP-9; ↓Galectin-3 | Zhang et al., 2016 [211] |
| U87MG, U373MG | 10–90 µM (24 h) |
Decreased cell proliferation, migration, and invasion | ↑ERK1/2; ↑CD44v6; ↓MMP-2 | Li et al., 2014 [212] |
| Skin cancer | ||||
| ME-18 | 1–5 µM (24, 48 h) |
Induced cell growth arrest | ↑Apoptosis; ↑DNA strand breaks; ↑PS externalization | Misiewicz et al., 2003 [191] |
| A375, 501MEL | 1–5 µg/mL (2–48 h) |
Suppressed cell growth, invasion, and metastasis | ↑Apoptosis; ↑MDM2; ↑BAX; ↑PUMA; ↑GADD45A; ↓CDKN1A; ↑FAS; ↑caspase-3; ↑caspase-8; ↑caspase-9; ↓Bcl2; ↑BBC3; ↓ADORA1; ↑HMOX1; ↑TXNRD1; ↑GGLC; ↑GCLM;↑AKR1B10; ↑G6PD; ↑HTRA3; ↓FST; ↓ITGB4; ↓PLAT; ↓ITGB2; ↓G2/M phase; ↑CDKN1A; ↑EGR1; ↑GADD45B; ↑ATF3 | Arcidiacono et al., 2018 [83] |
| A375 | 2 µg/mL (24–72 h) |
Shifted growth factor receptor ratio from prosurvival to proapoptotic | ↑Apoptosis | Arcidiacono et al., 2018 [213] |
| A375 | 0.1–100 µM (24, 48 h) |
Decreased cell survival | ↑Apoptosis; ↑caspase-3; ↑caspase-4; ↑caspase-6; ↑caspase-7; ↑caspase-8; ↑caspase-9 | Mantso et al., 2016 [214] |
| A375 and WM793 | 1–20 µM (24, 48 h) |
Reduced spheroid formation, migration, and invasion | ↑Apoptosis; ↓Ezh2; ↓H3K27me3; ↓Bmi-1; ↓Suz12 | Fisher et al., 2016 [215] |
| B16F-10 | 1–5 µg/mL | Reduced cell viability and proliferation | ↑Apoptosis; ↑caspase-3; ↑caspase-9; ↑Bax; ↑p53; ↓caspase-8; ↓Bcl-2; ↓Bid; ↓NF-κB; ↓IL-1β; ↓IL-6; ↓TNF-α; ↓IL-12p40; ↓GM-CSF; ↓p65; ↓p50; ↓c-Fos; ↓ATF-2; ↓CREB; ↓c-Rel | Hamsa et al., 2011 [216] |
| B16 | 20–50 µM (24–72 h) |
Reduced cell viability | ↓HDAC | Enriquez et al., 2013 [217] |
| B16 and S91 | 20–50 µM (24–72 h) |
Inhibited cell growth and proliferation | ↓HDAC | Do et al., 2010 [218] |
| Bowes and SK-MEL-28 | 5–100 µM (2–48 h) |
Decreased cellular proliferation | ↑Apoptosis; ↑p-p38 kinase; ↑p53; ↑PUMA; ↑Bax; ↑ROS | Rudolf et al., 2014 [219] |
| Urogenital cancers | ||||
| Bladder cancer | ||||
| T24 | 5–20 µM (24, 48 h) |
Inhibited cell proliferation | ↑Apoptosis; ↓S and G2/M phase cells; ↑p27 | Shan et al., 2006 [220] |
| T24 | 50–20 µM (4–24 h) |
Decreased cell growth | ↓COX-2; ↑nuclear NF-κB translocation; ↑p38 | Shan et al., 2009 [221] |
| T24 | 5–20 µM (10, 24 h) |
Inhibited cell growth | ↑TR-1 mRNA; ↑GSTA1 mRNA; ↓COX-2 | Shan et al., 2010 [222] |
| T24 | 5–20 µM (24 h) |
Decreased cell invasion and migration | ↑E-cadherin; ↓Snail; ↓ZEB1; ↑miR200c | Shan et al., 2013 [223] |
| T24 | 10, 20 µM (24 h) |
Inhibited cell growth | ↑Apoptosis; ↑caspase-3; ↑caspase-9; ↑PARP cleavage; ↓XIAP; ↓cIAP-1; ↓cIAP-2; ↑Bax; ↑cyt. c; ↑ER stress; ↑GRP78; ↑CHOP; ↑ROS; ↑Nrf2; ↓Keap1; ↑HO-1 | Jo et al., 2014 [224] |
| RT4, J82, UMUC3 | 5–100 µM (48 h) |
Inhibited cell proliferation | ↑Apoptosis; ↓NHU; ↑G2/M phase arrest; ↑caspase-3; ↑caspase-7 activity; ↑PARP cleavage; ↓survivin; ↓EGFR; ↓HER2/neu | Abbaoui et al., 2012 [82] |
| RT4, J82, UMUC3 | 4–20 µM (3–48 h) |
Decreased cell growth | ↓HDAC; ↑p21 (RT4 cells); ↓thymidylate synthase; ↓histone H1 phosphorylation; ↑PP1β; ↑PP2A | Abbaoui et al., 2017 [225] |
| BIU87 | 10–80 µM (24 h) |
Decreased cell proliferation | ↑Apoptosis; ↑G2/M phase arrest; ↑IGFBP-3 mRNA; ↓NF-κB | Dang et al., 2014 [226] |
| 5637 | 20 µM (4–48 h) |
Suppressed cell growth | ↑Apoptosis; ↑G2/M phase arrest; ↑histone H3 phosphorylation; ↑cyclin B1; ↑Cdk1; ↑caspase-3; ↑PARP cleavage; ↑MMP loss; ↑ROS | Park et al., 2014 [227] |
| Prostate cancer | ||||
| LNCaP, MDA PCa 2a, MDA PCa 2b, PC-3, TSU-Pr1 | 0.1–0.15 µM (1–72 h) |
Reduced cellular proliferation | ↑NQO1; ↑QR; ↑γ-GCS-L; ↑GSH; ↑microsomal GST; ↑α-class GSTs | Brooks et al., 2001 [228] |
| DU145, LNCaP, PC-3, and CWR22Rv1 | 20, 40 µM (12, 24 h) |
Reduced cell viability | ↑Apoptosis; ↓p-STAT3; ↓IL-6-induced STAT3 phosphorylation; ↓JAK2; ↓pSTAT3 nuclear translocation; ↓STAT3 dimerization; ↓Bcl-2; ↓cyclin D1; ↓survivin; ↓Mcl-1 | Hahm et al., 2010 [229] |
| LNCaP, PC-3 | 10–40 µM (2–24 h) |
Reduced cell growth and proliferation | ↑Apoptosis; ↑p53; ↑Bax; ↑E2F1; ↑Apaf-1; ↓Bak; ↓Bcl-xL; ↓NF-κB; ↓cIAP1; ↓cIAP2; ↓XIAP | Choi et al., 2007 [230] |
| LNCaP | 1, 10 µM (24–72 h) |
Reduced cell viability and growth | ↑Apoptosis; ↓Bcl-xL; ↓glycolysis; ↓HIF-1α; ↓nuclear AR; ↓PSA | Carrasco-Pozo et al., 2019 [231] |
| LNCap, C4-2 | 1–40 µM (24, 48 h) |
Inhibited androgen-stimulated cell growth and proliferation | ↑Transcriptional repression of AR; ↓total AR; ↓Ser210/213 phosphorylated AR; ↓intracellular PSA; ↓secreted PSA | Kim and Singh, 2009 [232] |
| PC-3, LNCaP | 40 µM (16 h) |
Reduced cell viability and promoted cell death | ↑Apoptosis; ↑autophagy; ↑LC3; ↑cyt. c | Herman-Antosiewicz et al., 2006 [233] |
| LNCaP, PC-3 | 20 µM (24 h) |
Inhibited cell growth and proliferation | ↑Apoptosis; ↑autophagy; ↑LC3 cleavage; ↑ROS; ↑G2/M phase arrest; ↑cyt. c; ↑Bax; ↓Bcl-2; ↓respiratory chain activity | Xiao et al., 2009 [234] |
| LNCaP, PC-3 | 150, 300 µM (4 h) |
Decreased cell proliferation | ↑Apoptosis; ↑autophagy; ↑LC3-II; ↓p62 | Watson et al., 2015 [235] |
| DU145 | 5–20 µM (24, 48 h) |
Inhibited cell viability | ↑Apoptosis; ↑G2/M phase arrest; ↑PARP cleavage; ↑ROS; ↑JNK | Cho et al., 2005 [236] |
| PC-3 | 10–40 µM (24 h) |
Reduced cell viabilityand proliferation | ↑Apoptosis; ↑DNA double-strand breaks; ↑S-phase arrest | Hac et al., 2020 [237] |
| LNCaP | 20–100 µM (24 h) |
Decreased cell viability and growth | ↑Apoptosis; ↑PARP cleavage; ↑caspase-3; ↓PGM3 | Lee et al., 2010 [238] |
| PC-3 | 20–100 µM (24–72 h) |
Reduced cell survival and proliferation | ↑Apoptosis; ↑G0/G1 arrest; ↑caspase-3; ↑caspase-8; ↑caspase-9; ↑Bax; ↑PARP cleavage; ↓Bcl-2 | Singh et al., 2004 [239] |
| PC-3, DU145 | 10–40 µM (1–24 h) |
Reduced cell viability | ↑Apoptosis; ↑caspase-3; ↑caspase-9; ↑Bid cleavage; ↑PARP cleavage; ↑Fas; ↑cyt. c; ↑disruption of mitochondrial membrane potential; ↑ROS; ↓GSH | Singh et al., 2005 [240] |
| PC-3 | 5–20 µM (24–96 h) |
Reduced cell viability | ↑Apoptosis; ↑NRF1; ↑mitochondrial fission; ↑Bax; ↑PGC1α; ↓HIF-1α | Negrette-Guzmán et al., 2017 [241] |
| 22Rv1 | 5–50 µM (3–24 h) |
Inhibited cell growth | ↑Apoptosis; ↓USP14 and UCHL5 active sites; ↑USP14; ↑UCHL5 protein; ↑Ub-Prs | Ahmed et al., 2018 [97] |
| LNCaP, PC-3 | 15 µM (6, 24 h) |
Inhibited cell proliferation | ↑HO-1; ↑NQO1; ↓BMX; ↓CDK2; ↓PLK1; ↓Sp1 | Beaver et al., 2014 [242] |
| LNCaP | 10, 25 µM (2–72h) |
Reduced cell growth | ↑Apoptosis; ↑NQO1; ↑LTB4DH; ↑ME1; ↑TXNRD1; ↑GSTM1; ↑MGST1; ↑SOD1; ↑PRDX1; ↑GCLM; ↓Jun; ↑G2/M arrest | Bhamre et al., 2009 [243] |
| LNCaP, PC-3 | 15 µM (24, 48 h) |
Inhibited cellular growth | ↑Ac-H3 at P21 promoter; ↑p21; ↑G2/M phase arrest; ↑HO-1; ↑NQO1; ↓HDAC3; ↓HDAC4; ↓HDAC6 | Clarke et al., 2011 [71] |
| LNCaP, VCaP | 10–20 µM (12, 24 h) |
Decreased cell viability | ↑HSP90 acetylation; ↓AR; ↓HDAC6; ↓ERG | Gibbs et al., 2009 [244] |
| LNCaP, PC-3 | 15 µM (48 h) |
Promoted cell cycle arrest and death | ↓HDAC activity; ↑Ac-H3; ↑Ac-H4; ↑caspase-3; ↑G2/M arrest | Myzak et al., 2006 [245] |
| TRAMP C1 | Exhibited cytotoxicity | ↑Nrf2; ↑NQO-1; ↑Ac-H3; ↓DNMT1; ↓DNMT3a; ↓HDAC1; ↓HDAC4; ↓HDAC5; ↓HDAC7 | Zhang et al., 2013 [246] | |
| LNCaP, PC-3 | 15 µM (3–24 h) |
Decreased cellular proliferation | Altered ~100 lncRNA’s expression | Beaver et al., 2017 [247] |
| PC-3, LNCaP | 10, 20 µM (8–24 h) |
Reduced cell proliferation and migration | ↓Notch1; ↓Notch2; ↓Notch4; ↑DNA fragmentation | Hahm et al., 2012 [248] |
| PC-3, LNCaP | 15, 30 µM (24, 48 h) |
Decreased cellular proliferation | ↓DNMT1; ↓DNMT3b; ↓cyclin-D2-promoter methylation; ↑cyclin D2 | Hsu et al., 2011 [249] |
| LNCaP, PC-3 | 15 µM (48 h) |
Exhibited cytotoxicity | ↓DNMT1; ↓DNMT3b; ↑CCR4; ↑TGFBR1 | Wong et al., 2014 [250] |
| LNCaP, PC-3 | 2.5–20 µM (24 h) |
Decreased cell viability and proliferation | ↑Apoptosis; ↓pCSC; ↓CD24; ↓ITGA6; ↓ZEB2; ↓c-Myc | Vyas et al., 2016 [251] |
| LNCaP, PC-3 | 15 µM (6–24 h) |
Decreased cell viability | ↑SUV39H1 post-translational modification; ↓H3K9me3; ↓chromatin-associated SUV39H1 | Watson et al., 2014 [252] |
| LNCaP, 22Rv1, PC-3 | 5, 10 µM (24 h) |
Decreased cell viability | ↓Glycolysis; ↓HKII; ↓LDHA; ↓PMK2 | Singh et al., 2019 [253] |
| DU145 | 5–40 µM (24 h) |
Decreased cell viability, migration, and invasion | ↓Pseudopodia; ↓MMP-2; ↑p-ERK1/2; ↑E-Cadherin; ↓CD44v6 | Peng et al., 2015 [254] |
| PC-3, DU145 | 10, 20 µM (24 h) |
Decreased cell proliferation and migration | ↑Apoptosis; ↑Vimentin; ↑PAI-1; ↓E-cadherin | Vyas and Singh, 2014 [255] |
| PC-3 | 40 µM (3–24 h) |
Inhibited cell viability | ↑Autophagy; ↓S6K1 phosphorylation; ↑LC3 | Hac et al., 2015 [256] |
| PC-3 | 5–50 µM (24 h) |
Decreased cell viability | ↑H2S; ↑p38; ↑JNK | Pei et al., 2011 [257] |
| PC-3 | 10–40 µM (2–24 h) |
Decreased cell survival | ↓Protein synthesis; ↓[3H]-leucine incorporation; ↓mTOR signaling; ↑S6K1 dephosphorylation; ↓survivin | Wiczk et al., 2012 [258] |
| PC-3 | 1–40 µM (24 h) |
Decreased cell viability | ↓NF-κB; ↓p65 nuclear translocation; ↓VEGF; ↓cyclin-D1; ↓Bcl-xL; ↓IKKα phosphorylation; ↓IKKβ phosphorylation | Xu et al., 2005 [259] |
| PC-3 | 5–40 µM (6–24 h) |
Reduced cell viability | ↑AP-1; ↑p-ERK1/2; ↑p-JNK1/2; ↑p-Elk-1; ↑p-c-Jun | Xu et al., 2006 [260] |
| DU145 | 5–40 µM (24 h) |
Inhibited angiogenesis | ↓HIF-1α; ↑JNK signaling; ↑ERK signaling; ↓VEGF | Yao et al., 2008 [261] |
| LNCaP, 22Rv1 | 5, 10 µM (8–24 h) |
Inhibited cell proliferation | ↓ACC1; ↓FASN; ↓CPT1A; ↓ACADVL; ↓ACADM; ↓HADHA; ↓SREBP1 | Singh et al., 2018 [262] |
| LNCaP | 10–60 µM (24 h) |
Promoted cell cycle arrest and death | ↑G2/M arrest; ↑S phase arrest; ↑mitotic arrest; ↓cyclin D1; ↓cyclin E1; ↓Cdk4; ↓Cdk6; ↓Cdk1; ↓Cdc25C; ↑cyclin B1; ↑p53; ↑p21 | Herman-Antosiewicz et al., 2007 [263] |
| LNCaP, DU-145 | 15 µM (24 h) |
Reduced cellular proliferation | ↓hTERT; ↓G0/G1 transition; ↓S phase; ↓NF-κB; ↓HDAC inhibitor activity; ↓H3K4me2 signal; ↓MeCP2; ↑H3K18Ac signal ↑DNMT1; ↑DNMT3a; ↑Pan-acetylated H3; ↑Pan-acetylated H4 | Abbas et al., 2016 [264] |
Symbols: ↑, increased or upregulated; ↓decreased or downregulated.