TABLE 3.
Drug resistance to chemotherapeutic agents reversed by AKR inhibitors
| Platinum-Based Drugs | ||||
|---|---|---|---|---|
| AKR | AKR Inhibitors | Chemotherapeutic Drug Resistance Inhibited | Cancer/Cell Line | Reference |
| AKR1B1 | 1-Benzyl-3-hydroxy-2(5H)-oxopyrrole-4-carboxylate (EBPC) | Cis-platin | Cervical cancer HeLa |
(Lee et al., 2002) |
| AKR1C1, AKR1C2, AKR1C3, AKR1C4 | Mefenamic acid | + mouse xenograft | (Shiiba et al., 2017) | |
| AKR1C1 AKR1C3 |
3-Bromo-5-phenylsalicylic acid (AKR1C1) Tolfenamic acid (AKR1C3) |
Colon cancer HCT15 |
(Matsunaga et al., 2013) | |
| AKR1C1, AKR1C2, AKR1C3, AKR1C4 |
Mefenamic acid | Oral squamous cell carcinoma Sa3 | (Shiiba et al., 2017) | |
| AKR1C1 | 3-Bromo-5-phenylsalicylic acid (Ki = 4 nM) | Head and neck squamous carcinoma 293 T, FaDu Cal-27, HSC-2 and HSC-4 |
(Chang et al., 2019) | |
| AKR1C1 | Flufenamic acid | Metastatic bladder cancer UM-UC-3 |
(Matsunaga et al., 2016a) | |
| AKR1C1, AKR1C2, AKR1C3 |
Phenolphthalein α-methylcinnamic acid, Flufenamic acid |
Oxaliplatin | Gastro-intestinal tract cancer TSGH | (Chen et al., 2013) |
| Anthracyclines | ||||
| AKR1B1 | 1-Benzyl-3-hydroxy-2(5H)-oxopyrrole-4-carboxylate | Doxorubicin | Cervical cancer HeLa |
(Lee et al., 2002) |
| AKR1C2 | 5β-Cholanic acid-3α,7α-diol | Breast cancer MCF-7 |
(Veitch et al., 2009) | |
| AKR1B10, AKR1C3, AKR1C2 | 5β-Cholanic acid-3α,7α-diol | Breast cancer MCF-7 | (Heibein et al., 2012) | |
| AKR1B10 | Oleanoic acid 3-(4-hydroxy-2-methoxyphenyl-1)acrylic acid 3-(3-hydroxyphenyl)propyl ester |
Gastric cancer MKN45 |
(Morikawa et al., 2015) | |
| AKR1C1 AKR1C3 |
3-Bromo-5-phenylsalicylic acid, Tolfenamic acid, |
Daunorubicin | Leukemia (acute monocytic leukemia) U937 |
(Matsunaga et al., 2014) |
| AKR1B10 AKR1C3 |
Emodin | Lung cancer A-549 Liver cancer Hep-G2 |
(Hintzpeter et al., 2016) | |
| AKR1C3 | Purvalanol A Roscovine | Colon cancer HCT 116 |
(Novotná et al., 2018a) | |
| Dinaciclib | (Novotná et al., 2018a, 2018b) | |||
| AKR1C3 | Irutinib Acalabrutinib Buparlisib |
Colon cancer HCT 116 |
(Morrell et al., 2020) (Bukum et al. 2019) |
|
| AKR1B10 | Epalrestat | Daunorubicin, Idarubicin |
Lung cancer NCI-H460 | (Zhong et al., 2011) |
| AKR1C3 | 2-Hydroxyflavanone | Lung cancer A-549 |
(Hofman et al., 2014) | |
| Other drugs | ||||
| AKR1B10 | (Z)-2-(4-methoxyphenyl-imino)-7-hydroxy-N-(pyridin-2-yl)-»H-chromene-3-carbox-amide | Mitomycin-c | Colon cancer HT-29 |
(Matsunaga et al., 2011) |
| AKR1C3 | Baccharin derivatives | Etoposide | Leukemia (acute myeloid leukemia) HL-60, KG-1a |
(Verma et al., 2016) |
| AKR1C1, AKR1C2, AKR1C3 |
6-Medroxy-progesterone acetate | Vincristine | Leukemia (acute lymphoblastic leukemia) CCRF-CEM, DND-41, Loucy |
(Bortolozzi et al., 2018) |
| AKR1C1, AKR1C2, AKR1C3, AKR1C4 | Mefenamic acid | 5-Fluoro uracil | Cervical cancer HeLa + mouse xenograft |
(Shiiba et al., 2017) |
| AKR1C3 | 1,3,5-Trisubstituted amido cinnamic acids Compounds Kv-49a, Kv-49g |
Cytarabine | Leukemia (acute myeloid leukemia) HL-60, TMP-1, KG-1a (T-cell acute lymphoblastic leukemia) primary cells |
(Verma et al., 2019) |
| AKR1C3 | Tolfenamic acid | Irinotecan | Colon cancer cell lines DLD1, RKO, LoVo | (Matsunaga et al., 2020) |
| Antihormone Therapy | ||||
| AKR1C3 | Indomethacin | Enzalutamide Abiraterone Acetate |
Castration resistant prostate cancer | (Liu et al., 2015; 2017) |
| AKR1C3 | Kv-37 and related Baccharin analogs | Enzalutamide | Castration resistant prostate cancer | (Verma et al., 2018) |
| 1,3,5-Trisubstituted amido cinnamic acids Compound Kv-49g |
Apalutamide Darolutamide |
Castration resistant prostate cancer | (Morsy & Trippier, 2020) | |