TY - JOUR ID - 31197 TI - Aldose Reductase Inhibitor Fidarestat as a Promising Drug Targeting Autophagy in Colorectal Carcinoma: a Pilot Study JO - Asian Pacific Journal of Cancer Prevention JA - APJCP LA - en SN - 1513-7368 Y1 - 2015 PY - 2015 VL - 16 IS - 12 SP - 4981 EP - 4985 KW - Aldose reductase KW - Autophagy KW - colorectal cancer KW - Drug KW - fidarestat KW - Therapeutics DO - N2 - Background: Colorectal cancer (CRC) is a leading cause of morbidity and mortality worldwide. Targetingautophagic cell death is emerging as a novel strategy in cancer chemotherapy. Aldose reductase (AR) catalyzesthe rate limiting step of the polyol pathway of glucose metabolism; besides reducing glucose to sorbitol, ARreduces lipid peroxidation-derived aldehydes and their glutathione conjugates. A complex interplay betweenautophagic cell death and/or survival may in turn govern tumor metastasis. This exploratory study aimed toinvestigate the potential role of AR inhibition using a novel inhibitor Fidarestat in the regulation of autophagy inCRC cells. Materials and Methods: For glucose depletion (GD), HT-29 and SW480 CRC cells were rinsed withglucose-free RPMI-1640, followed by incubation in GD medium +/- Fidarestat (10μM). Proteins were extractedby a RIPA-method followed by Western blotting (35-50 μg of protein; n=3). Results: Autophagic regulatorymarkers, primarily, microtubule associated protein light chain (LC) 3, autophagy-related gene (ATG) 5, ATG 7and Beclin-1 were expressed in CRC cells; glyceraldehyde-3 phosphate dehydrogenase (GAPDH) was used asan internal reference. LC3 II (14 kDa) expression was relatively high compared to LC3A/B I levels in both CRCcell lines, suggesting occurrence of autophagy. Expression of non-autophagic markers, high mobility group box(HMG)-1 and Bcl-2, was comparatively low. Conclusions: GD +/- ARI induced autophagy in HT-29 and SW-480cells, thereby implicating Fidarestat as a promising therapeutic agent for colorectal cancer; future studies withmore potent ARIs are warranted to fully dissect the molecular regulatory networks for autophagy in colorectalcarcinoma. UR - https://journal.waocp.org/article_31197.html L1 - https://journal.waocp.org/article_31197_84f34ae3298d78b22a89b489a44c3cfe.pdf ER -