Table 4 Examples of the pharmacological compounds or therapeutical procedures found to improve PCa in human cell lines by modulating the autophagy process
Drug/ compound/ procedure | In vitro/In vivo | Cell line(s) | Animal model | Target pathway(s) affecting autophagy | Effect on autophagy | Finding(s) | Ref(s) |
|---|---|---|---|---|---|---|---|
Icariside II | In vitro | DU145 | - | Modulating the PI3K/AKT/mTOR pathway | ↑ | Suppressed human prostate tumor cell proliferation and migration | [222] |
Valproic acid | In vitro | PC3, DU145 and LNCaP | - | Inhibiting the Akt/mTOR pathway | ↑ | Suppressed the growth of PCa cells | [220] |
Sunitinib | In vitro | PC3 and LNCaP | - | Activating the ERK1/2 pathway- Inhibiting the mTOR/p70S6K pathway | ↑ | Inhibited PCa cell growth and induced autophagy- Increased apoptotic, and autophagic cell death | [227] |
Efavirenz (EFV) and SPV122.2 (Reverse transcriptase inhibitors) | In vitro | PC3 and LNCaP | - | - | ↑ | Decreased proliferation - Induced genome damage- Increased autophagy | [228] |
Benzyl isothiocyanate (BITC) | In vitro | Rv1, and PC3 | - | Inhibiting the mTOR pathway | ↑ | Induced apoptosis and autophagy in human PCa cells | [223] |
Qianlie Xiaozheng decoction | In vitro/In vivo | PC3 | Nude mice bearing PC3 xenografts | Inhibiting the Akt/mTOR pathway | ↑ | Accelerated cell death in PCa cells-Inhibited tumor growth in vivo in PC3 cell line | [224] |
Eriocalyxin B (EriB) | In vitro | PC3, and 22RV1 | - | Inhibiting the Akt/mTOR pathway | ↑ | Induced apoptosis and autophagy in PCa cells -Suppressed tumor cell proliferation. | [225] |
Neuregulin | In vitro | LNCaP | - | Activating JNK and Beclin 1 | ↑ | Induced incomplete autophagy and cell death in ROS level-dependent manner - Autophagy activation was independent of mTOR inhibition. | [226] |
Rottlerin | In vitro | Human prostate CSCs | - | Activating the AMPK pathway Inhibiting the Akt/mTOR pathway | ↑ | Induced autophagy, apoptosis, and cytoplasmic vacuolation in prostate CSCs | [229] |
Quercetin | In vitro | PC3 | - | Inhibiting the PI3K/AKT/mTOR pathway | ↑ | Inhibited cell viability in a dose-time dependent manner - Induced apoptosis | [230] |
Low frequency ultrasound | In vitro | PTX-resistant PC3 | - | ERs-mediated downregulation of the PI3K/AKT/mTOR pathway | ↑ | Induced apoptosis and autophagy- Enhanced chemosensitivity | [231] |
Propranolol + 2DG (glycolysis inhibitor) | In vitro/In vivo | PC3, LNCaP, and PNT1A (human immortalized prostatic cell line) | NOD SCID mice bearing PC3 xenografts | - | ↓ | In vitro: prevented cancer cell proliferation, induced cell apoptosis, altered the morphology of mitochondria, inhibited mitochondrial energetics, and aggravated ERs. In vivo: inhibited tumor growth | [232] |
Hydroxytyrosol | In vitro | PC3 | - | - | ↓ | Induced apoptosis and mitochondrial malfunction in PC3 cells through producing superoxide | [233] |
BEZ235 or PI103 (Dual PI3K/mTOR inhibitors) | In vitro | PC3 RR, DU145RR and LNCaPRR | - | Inhibiting the PI3K/AKT/mTOR pathway | ↓ | Improved radiosensitivity via increased rate of apoptosis, inhibition of autophagy, and suppression of the DNA repair mechanisms (NHEJ and HR) | [234] |
Cytolethal distending toxin | In vitro | LAPC4 | - | Downregulating c-Myc expression Reducing HMGB1 | ↓ | Improved radiosensitivity - Prolonged radiation-induced DSBs – Suppressed autophagy | [235] |