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. 2019 Apr 11;8(5):R91–R104. doi: 10.1530/EC-19-0114

Table 2.

Drugs that positively increased the ACC apoptosis rate in in vitro and in vivo studies.

Anti-ACC drugs Drug type Method to evaluate apoptosis Samples type Ref.
AMG 900 Aurora kinase inhibitor Annexin V-FITC apoptosis detection assay ACC cell line NCI-H295 (141)
ATR-101 (PD132301-02) Adrenalytic activity inhibitor TUNEL assay NCI-H295R xenographs (142)
Annexin V-FITC apoptosis detection assay ACC cell line NCI-H295R
Cholesterol free sHDL nanoparticles in combination with cisplatin, etoposide or mitotane efflux cholesterol inducer Annexin V-FITC apoptosis detection assay ACC cell lines: SW-13 and NCI-H295R (143)
Docosahexenoic acid n-3 polyunsaturated fatty acid/mTOR complex 1/2 inhibitor Annexin V-FITC Apoptosis Detection assay ACC cell lines: SW-13 and NCI-H295R (144)
TUNEL assay SW-13 xenographs
DZNep EZH2 (histone modifier) inhibitor BCL2, BCL-XL and BIRC5 expression/Caspase 3 activity assay/TUNEL assay ACC cell line NCI-H295R (145)
Erlotinib and NVP-AEW541 combination EGFR and IGF1R inhibitor Annexin V-FITC apoptosis detection assay ACC cell lines: SW-13 and NCI-H295R (134)
Fingolimod (FTY720) Sphingosine kinase 1 antagonist Annexin V-FITC apoptosis detection assay ACC cell lines: SW-13 and NCI-H295R (146)
G-1 Non-steroidal G protein-coupled estrogen receptor agonist Annexin V-FITC Apoptosis Detection assay/Caspase 9 and 3/7 activity assay/TUNEL assay ACC cell line NCI-H295R (147)
Metformin Biguanide cationic agent Annexin V Apoptosis Detection assay/Bcl-xl, Bcl-2, Bcl-w and Cleaved Caspase 3 expression ACC cell line NCI-H295R (148)
Mitotane (drug used in ACC patients) Steroidogenesis inhibitor and cytostatic antineoplastic Annexin V Apoptosis Detection assay/Bax, Bak and Bcl-2 expression ACC cell line NCI-H295 (149, 150)
Caspase 3/7 activity assay ACC cell line NCI-H295R (151)
Niclosamide Anti-helminthic agent Caspase 3/7 activity assay ACC cell lines: BD140A, SW-13 and NCI-H295R (152)
Rapamycin mTOR complex 1 inhibitor Cleaved Caspase 3 expression Adrenocortical tumors from AdTAg mice (153)
Rottlerin Anti-helminthic or fertilization antagonist TUNEL assay SW-13 xenographs (133)
Annexin V-FITC Apoptosis Detection assay ACC cell lines: SW-13 and NCI-H295R

ACC, adrenocortical carcinomas; AMG, urora kinases inhibitor; Bak, B-cell lymphoma 2 homologous antagonist/killer; Bax, B-cell lymphoma 2-associated X protein; BCL-2, B-cell lymphoma 2; BCL-W, B-cell lymphoma-like 2; BCL-XL, B-cell lymphoma-extra-large; BIRC5, Baculoviral IAP repeat containing 5; DZNep, Deazaneplanocin A; EGFR, epidermal growth factor receptor; EZH2, enhancer of zeste homolog 2; FITC, fluorescein isothiocyanate; IGFR, insulin growth factor receptor; mTOR, mammalian target of rapamycin; NCI, National Cancer Institute; sHDL, synthetic high-density lipoprotein; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling.