Table 1. anti-Ras compounds inducing autophagy in cancer cells.
| Drug tested | Cancer model | Mechanism of anticancer effect | Mechanism of autophagy induction | Role of autophagy in cancer cells | Mode of autophagy inhibition tested |
|---|---|---|---|---|---|
| Manumycin A, lonafarnib and FTI-276 [63] | Pancreatic cancer and osteosarcoma cell lines | Inhibition of farnesyltransferase; decreases Ras farnesylation and inhibits Ras anchorage to the cell membrane. | Not tested | Uncertain | Pharmacological: 3-MA |
| FTI-1 [64] | Malignant peripheral nerve sheath tumor and murine hepatoma cell lines | Inhibition of farnesyltransferase; decreases Ras farnesylation and inhibits Ras anchorage to the cell membrane. | Not tested | Cell destructive | - |
| FTS [70, 71] | Colon adenocarcinoma, cervical cancer and pancreatic cancer cell lines; mouse fibroblasts | Mimicking the farnesyl group of Ras; dislodges Ras from the cell membrane. | mTOR1 inhibition (possibly) | Cell protective |
Pharmacological: 3-MA, Chloroquine Genetic: knockout of ATG5 |
| Cysmethynil [72] | Prostate cancer cell line | Inhibition of Icmt1; decreases Ras methylation and leads to mislocalization of Ras. | mTOR1 inhibition | Cell destructive |
Pharmacological: 3-MA Genetic: knockdown of Atg5 |
| Cysmethynil [73] | hepatocellular carcinoma and breast cancer cell lines; mouse fibroblasts | Inhibition of Icmt1; decreases Ras methylation and leads to mislocalization of Ras. | Not tested | Cell destructive |
Pharmacological: 3-MA Genetic: knockdown of Atg5 or Atg1/ULK1; knockout of ATG5 |
| Methotrexate [74] | Osteosarcoma cell lines | Inhibition of Icmt1; decreases Ras methylation and disrupts its proper localization. | Class III PI3K complex activation (dependent upon ULK1/Atg13/FIP200 complex formation) | Cell protective | Genetic: knockdown of beclin 1 or Atg7 |