piperlongumine

Piperlongumine is a naturally occurring alkaloid isolated primarily from the fruit of Piper longum (long pepper). This small molecule has demonstrated potent and selective cytotoxicity against a broad array of cancer cell lines, including breast, pancreatic, thyroid, and non-small cell lung cancer cells, while sparing normal cells[1][4][9]. The anticancer effects of piperlongumine are mainly attributed to its ability to increase intracellular reactive oxygen species (ROS) levels by directly inhibiting the antioxidant enzyme glutathione S-transferase Pi 1 (GSTP1), leading to apoptosis and cell death in cancer cells[1]. Piperlongumine also inhibits signal transducer and activator of transcription 3 (STAT3) nuclear translocation and phosphorylation, modulates STAT3-regulated gene expression, and effectively inhibits tumor cell proliferation and tumorigenesis in xenograft mouse models[4][6]. Additional mechanisms include induction of autophagy, cell cycle arrest, and ferroptosis[1]. Piperlongumine has been shown to overcome resistance to chemotherapeutic agents and targeted therapies, such as cisplatin and osimertinib, by inhibiting Akt phosphorylation through ROS accumulation and reversing drug resistance in non-small cell lung cancer models[3][7]. Preclinical studies demonstrate low toxicity in normal tissues and favorable tolerability in animal models[3][4][6]. While widely studied in cancer biology, piperlongumine remains in preclinical and early clinical development stages and is not approved for clinical use[2][6].

Other names

1-[(2E)-3-(3,4,5-Trimethoxyphenyl)-2-propenoyl]-5,6-dihydro-2(1H)-pyridinonePLPPL