Table 1 6-Shogaol in vitro anticancer study (“↑” represents increase/promotion/activation while “↓” represents inhibition/reduction/inactivation. “-”Indicates not indicated.)
Cancer models | Cell lines | Mechanisms | Concentration used | IC50 | Ref. |
|---|---|---|---|---|---|
Breast cancer | MCF-7 MDA-MB-231 | Induce G2/M phase cell cycle arrest Induce apoptosis: Notch1↓ Hes↓ cyclinD1↓ Induce cell autophagy | 1–100 μM | MCF-7 7.94 ± 0.57 μM MDA-MB-231 5.67 ± 0.73 μM | [12] |
T47D | Induce cell autophagy Induce apoptosis Induce G2/M phase cell cyclearrest: Notch↓ Hes1↓ CyclinD1↓ | 0–100 μM | 0.5 ± 0.1 μM | [35] | |
MCF-7 MDA-MB-231 | Inhibit cancer cell invasion Inhibit NF-kB cascade activation: MMP-9↓ p-JNK↓ p–c-jun↓ p65↓ | 5–30 μM | _ | [36] | |
MDA-MB-231 | Induce ER stress: polyubiquitinated proteins↑ Bip↑ CHOP↑ Induce G1 phase cell cycle arrest | 0–50 μM | 22.1 ± 0.4 μM | [37] | |
Liver cancer | SMMC-7721 | Induce apoptosis: p-elF2α↓ CHOP↑ | 0–20 μM | _ | [38] |
HepG2 Huh-7 | Induce G2/M phase cell cycle arrest: CyclinA↓、CyclinB1↓、CyclinD1↓ CyclinE1↓ cdc2↓ cdc25↓ Induce apoptosis: Caspase-3↑ ROS↑ ERK↓ p38↓ JNK↓ Induce autophagy: ER stress ROS↑ LC-3II↑ GRP78↑ p-eIF2aα↑ p-Akt↓ p-AMPK↓ | 10–60 μM | HepG2 50 μM Huh-7 60 μM | [15] | |
HepG2 Li-7 | Induce apoptosis: MRP1↓ Induce G0/G1 cell cycle arrest: AKT/mTOR/MRP1↓ CyclinA2↓ Cyclin D1↓ Cyclin E1↓ | 10–50 μM | _ | [39] | |
Hep3B | Inhibit invasion and metastasis: MAPK↓ PI3k/Akt↓ NF-kB↓ STAT3↓ | 10–50 μM | _ | [40] | |
Cervical cancer | HeLa SiHa | Induce apoptosis: p-PI3K↓ p-Akt↓ p-mTOR↓ Induce G2/M phase arrest Inhibit metastasis: N-cadherin↓ Snail↓ Twist↓ Zeb-1↓ Zeb-2↓ | 0–160 μM | HeLa 25.68 ± 0.47 μM SiHa 37.52 ± 1.56 μM | [13] |
HeLa | Induce apoptosis: ER stress、Bax↑ Caspase-3↑ PARP↓ Induce G2/M phase arrest | 5–80 μM | 14.75 ± 0.94 μM | [41] | |
Colon cancer | SW480 SW620 | Induce apoptosis Induce G2/M phase arrest | 0–80 μM | 20 μM | [30] |
HT-29 | Induce G2/M phase arrest Induce apoptosis: survivin↓ Bcl-2↓ Bax↑ | 0–80 μM | 40 μM | [42] | |
HT-29 HCT116 | Induce apoptosis: PPARγ↑ NFκB↓ | 0–100 μM | _ | [43] | |
Oral cancer | YD-10B Ca9-22 | Induce apoptosis: p-PI3K↓ p-AKT↓ p-mTOR↓ p53↓ caspase-3↓ Bcl-2↓ Bax↑ Inhibit cell proliferation: PI3K/AKT↓ | 0–20 μM | _ | [44] |
Kidney cancer | 786-O | Inhibit PhIP-mediated osteoclastogenesis and bone resorption: IL-8↓ PTHrP↓ RANKL↓ | 2 mM | _ | [16] |
Caki | Induce apoptosis: MMP↓ c-FLIP(L) ↓ ROS↑ | 0–20 μM | _ | [45] | |
Non-small cell lung cancer | A549 | Induce cell death via pyroptosis | 0–50 μM | 29.6 ± 2.1 μM | [37] |
A549 | Induce autophagy: AKT↓ mTOR↓ GSK-3β↓ FKHR↓ | 0–50 μM | _ | [46] | |
A549 | Induce apoptosis: GSH↑ p53↑ PUMA↑ Bcl-2↓ Bcl-XL↓ | 0–80 μM | 25.17 μM | [47] | |
A549 | Induce apoptosis: GSK3β / β-catenin↓ mPGES-1↓ | 25–240 μM | _ | [48] | |
NCI-H1650 NCI-H520 NCI-H1975 | Induce G1 or G2/M phase arrest Induce apoptosis: caspase-3↑ caspase-7↑ AKT↓ p-STAT3↓ | 0–20 μM | _ | [49] | |
H-1299 | Induce apoptosis | 0–80 μM | 25.8 μM | [50] | |
Prostate cancer | LNCaP DU145 PC3 | Induce apoptosis: STAT3↓ NF-KB↓ cyclin D1↓ survivin↓ cMyc↓ Bcl-2↓ Bax↑ p21↑ p27↑ SOCS1↑ IRF1↑ Anti-inflammatory: IL-7↓ CCL5↓ | 0–40 μM | _ | [33] |
PC-3 | Induce apoptosis: COX-2↓ MAPK↓ PI3K/Akt↓ cyclin D1↓ MMP-9↓ caspase↓ | 0–100 μM | _ | [18] | |
Leukaemia | Nalm-6 | Induce apoptosis: p53↑ p21↑ PUMA↑ FSAN↓ ROS↑ | 0–200 μM | 191.33 ± 2.96 μM | [51] |
Pancreatic cancer | BxPC-3 | Induce apoptosis: TLR4 / NF-κB↓ cIAP-1↓ survivin↓ XIAP↓ Bcl-2↓ caspase 3↑ COX-2↓ cyclin D1↓PARP↑ | 0–30 μM | 6.60 μM | [52] |
Human fibrosarcoma | HT1080 cell | Induce apoptosis: ROS↑ p-mTOR↑ p-Akt↑ | 2.5–150 μM | 52.8 μM | [34] |
Melanoma | B16F10 mouse melanoma cells | Inhibit melanin synthesis: ERK↑ Tyrosinase↓ | 1–10 μM | _ | [53] |