4'-Iodo-α-Pyrrolidinononanophenone Provokes Differentiated SH-SY5Y Cell Apoptosis Through Downregulating Nitric Oxide Production and Bcl-2 Expression.

Abuse of pyrrolidinophenone derivatives (PPs) is known to cause severe damage to the central nervous system due to their high lipophilicity. In this study, we compared sensitivity to toxicity elicited by 4'-iodo-α-pyrrolidinononanophenone (I-α-PNP), one of the most potent cytotoxic derivatives among PPs synthesized previously, between SH-SY5Y cells differentiated by all-trans-retinoic acid (ATRA) and the undifferentiated cells, and found that the differentiated cells are more sensitive to I-α-PNP toxicity than the undifferentiated cells. Treatment with I-α-PNP elicited some apoptotic alterations (Bax expression, loss of mitrochondrial membrane potential, and activation of caspases) in the differentiated cells, whose patterns were similar to those in the undifferentiated cells.

Development of cisplatin resistance in breast cancer MCF7 cells by up-regulating aldo-keto reductase 1C3 expression, glutathione synthesis and proteasomal proteolysis.

Cisplatin (CDDP) is widely prescribed for the treatment of various cancers including bladder cancers, whereas its clinical use for breast cancer chemotherapy is restricted owing to easy acquisition of the chemoresistance. Here, we established a highly CDDP-resistant variant of human breast cancer MCF7 cells and found that procuring the resistance aberrantly elevates the expression of aldo-keto reductase (AKR) 1C3. Additionally, MCF7 cell sensitivity to CDDP was decreased and increased by overexpression and knockdown, respectively, of AKR1C3, clearly inferring that the enzyme plays a crucial role in acquiring the CDDP resistance.