Table 1 In vitro studies of autophagy inhibiors on the TMZ anti-glioblastoma activity
From: Targeting autophagy to sensitive glioma to temozolomide treatment
Cell lines | Therapeutic methods (concentration /exprosure time) | Major findings | Interpretation | Reference |
|---|---|---|---|---|
Rat C6 cells | TMZ 100–1,000 μM/24 hours | CQ potentiated TMZ-induced cytotoxicity. | CQ increaseed cellular ROS in glioma cells by inhibiting mitochondrial autophagy. | [35] |
Human U87 cells | CQ 10 μM/24 hours | |||
Human LN229, U251 and U87 cells | TMZ 20–100 μM/48 hours | CQ increased the chemosensitivity of glioma cells to TMZ. | CQ blocked autophagy and triggered endoplasmic reticulum stress. | [48] |
CQ 10-25 μM/48 hours | ||||
Human GBM8901cells | TMZ 100 μM/24 hours | Chrysin induced apoptosis, suppressed migration and invasion, and sensitized GBM cells to TMZ. | Chrysin inhibited TMZ-induced autophagy and MGMT expression. | [75] |
Chrysin 20 μM/24 hours | ||||
Human U87, GBM8401 and GBM-SKH cells | TMZ 400 μM/72 hours | Resveratrol enhanced the therapeutic effect of TMZ against malignant glioma. | Coadministration of resveratrol and TMZ reduced tumor volumes by suppressing ROS/ERK-mediated autophagy. | [42] |
Resveratrol 10 μM/1 hours | ||||
Human U87, U251 and SHG‑44U87 cells | TMZ 100 μM/72 hours | ATM inhibitor ku-55933 enhanced TMZ cytotoxicity in inherently TMZ‑sensitive glioma cells. | Ku-55933 inhibited the phosphorylation of AMPK, and reduced the levels of TMZ-induced autophagy. | [54] |
Ku-55933 10 μM/72 hours | ||||
Human U87 and U251 cells | TMZ 100 μM/72 hours | TMZ chemoresistance was overwhelmed by targeting ATM. | Ku‑55933 inhibited the activation of ULK1 and interrupted the cytoprotective process of autophagy. | [55] |
Ku-55933 10 μM/72 hours | ||||
Human U-118 cells | TMZ 0–500 μM/24-48 hours | Inhibition of ERK1/2 partially eradicated the chemoresistance of U-118 GBM cells to TMZ. | ERK1/2 specific inhibitors U-0126 prevented the activation of autophagy by TMZ. | [19] |
U-0126 15 mM/48 hours | ||||
Human U87 cells | TMZ 400 μM/0–72 hours SP600125 10 μM/1 hours | TMZ-induced autophagy is mediated by JNK activation. | JNK inhibitor suppressed TMZ-induced JNK phosphorylation, further blocked autophagy and increased apoptosis. | [61] |
Human LN229 and U251 cells | TMZ 100 μM/24 hours | Targeting eEF-2 kinase can enhance the anti-glioma activity of TMZ. | Inhibition of eEF-2 kinase by SiRNA or NH125 blocked the activation of TMZ-induced autophagy. | [65] |
eEF-2 SiRNA N/A | ||||
NH125 0.5 μM/24 hours | ||||
Human U251 cells | TMZ 200 and 400 μM/72 hours | Inhibition of autophagy potentiated the cytotoxicity of curcumin or TMZ as well as TMZ/curcumin combination. | Autophagy inhibition sensitizes TMZ and curcumin treated cells to apoptosis. | [81] |
Curcumin 15 μM/72 hours | ||||
3-MA 4 mM/72 hours | ||||
Human U87 cells | TMZ 400 μM/36-72 hours | TMZ induced autophagy through mitochondrial damage- and ER stress-dependent mechanisms to protect glioma cells. | ETC inhibitors rotenone, sodium azide, oligomycin, or ER stress inhibitor 4-PBA reduced autophagy and consequently increased TMZ-induced apoptosis. | [61] |
rotenone 20 nM/1 hour | ||||
sodium azide 150 μM/1 hour | ||||
oligomycin 1 nM/1 hour | ||||
4-PBA 10mM/1 hour | ||||
Human U87 and U251 cells | TMZ 50–200 μM/48 hours | Targeting VAMP8 alleviated TMZ resistance in glioma cells. | silencing of VAMP8 by SiRNA could impaire the TMZ-induced autophagic flux. | [69] |
VAMP8 SiRNA N/A |