Rotenone Beyond Just An Insecticide: A Review

Abstract

Pesticides have received the most attention due to their global application and widespread implications on human health. In recent years, both epidemiological and toxicological studies have provided evidence that pesticides have the potential to act as toxicants contributing to the development of pathogenesis such as neuronal degenerations as well as may be utilized to induce signalling for reversal, suppress or prevent carcinogenic progression. Rotenone, an isoflavones naturally found in the roots and stems of several plants, is used as a broad-spectrum pesticide. Surprisingly, being a known toxicant, rotenone is used in organic food farming, based on its label as a natural product. Highly lipophilic, it easily crosses the cellular membrane without depending on a transmembrane protein. Once inside the cell, it accumulates at mitochondrial complex I where it is known to inhibit the transfer of electrons and increases reactive oxygen species (ROS) production, causing oxidative damage to DNA and proteins. More recently, rotenone was also shown to inhibit proteosome activity and catalyze the degradation of ubiquitin tagged proteins which may be implicated in pathogenesis of diseases. Numerous plant derived flavonoids compounds, with mitochondrial electron transport chain interrupter, such as rotenone, are currently used by cancer patients as dietary supplements to complement chemotherapy. Excess generation of ROS and its involvement in down-regulation of cellular proliferation by rotenone may be significant in chemotherapeutic assistance in prolonged treatment of tumourigenesis in future.

Keywords: Rotenone, Reactive oxygen species (ROS), Cancer, Mitochondrial dysfunction