Glutathione S-transferase P 1 (GSTP1)

Glutathione S-transferase P 1 (GSTP1) is a major Phase II detoxification enzyme belonging to the pi class of the glutathione S-transferase family [1, 3]. Its primary biological function involves catalyzing the conjugation of reduced glutathione (GSH) to a wide range of electrophilic and hydrophobic compounds, including environmental carcinogens and chemotherapeutic agents, thereby facilitating their excretion [1, 4]. Beyond its catalytic role, GSTP1 acts as a critical regulator of cellular signaling by forming protein-protein complexes with kinases such as c-Jun N-terminal kinase (JNK) and apoptosis signal-regulating kinase 1 (ASK1), effectively inhibiting stress-induced apoptosis [2, 6, 11]. In oncology, GSTP1 is frequently overexpressed in various malignancies, including lung, breast, and ovarian cancers, where it contributes significantly to multi-drug resistance (MDR) by detoxifying anticancer drugs and suppressing apoptotic pathways [6, 10, 11]. Conversely, the GSTP1 gene is often silenced via promoter hypermethylation in prostate cancer, making it a valuable diagnostic biomarker [3, 14]. Therapeutic strategies targeting GSTP1 include the use of inhibitors like ezatiostat to sensitize resistant tumors to chemotherapy and the development of prodrugs like canfosfamide that are selectively activated by the enzyme's catalytic activity [2, 11].

Other names

GSTP1-1GST piFatty Acid Ethyl Ester Synthase III (FAEES3)DFN7PIGST3HEL-S-22

Inhibition of enzymatic activity to reverse drug resistance and sensitize cells to chemotherapy; activation of glutathione-analog prodrugs via catalytic cleavage; disruption of GSTP1-kinase complexes to restore pro-apoptotic signaling [1, 2, 6, 11].