Journal
PHYTOMEDICINE
Volume 111, Issue -, Pages -Publisher
ELSEVIER GMBH
DOI: 10.1016/j.phymed.2023.154655
Keywords
Drug-resistant oral cancer; Plumbagin; Reactive oxygen species; Endoplasmic reticulum stress; Mitochondrial dysfunction
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This study demonstrated that plumbagin (PG), a natural compound isolated from Plumbago zeylanica L, exhibits anticancer effects against drug-resistant oral cancer cells by reducing cell viability, inducing apoptosis, and triggering intracellular and mitochondrial ROS generation, leading to mitochondrial dysfunction and endoplasmic reticulum stress. In addition, the inhibition of ROS abolished the effects of PG on cell viability, apoptosis, and ER stress.
Background: Oral cancer is one of the leading causes of cancer-related deaths worldwide. Chemotherapy is widely used in the treatment of oral cancer, but its clinical efficacy is limited by drug resistance. Hence, novel compounds capable of overcoming drug-resistance are urgently needed.Purpose: Plumbagin (PG), a natural compound isolated from Plumbago zeylanica L, has been used to treat various cancers. In this study, we investigated the anticancer effects of PG on drug-resistant oral cancer (CR-SAS) cells, as well as the underlying mechanism. Methods: MTT assays were used to evaluate the effect of PG on the viability of CR-SAS cells. Apoptosis and reactive oxygen species (ROS) production by the cells were determined using flow cytometry. Protein expression levels were detected by western blotting.Results: The results show that PG reduces the viability and causes the apoptosis of CR-SAS cells. PG is able to induce intracellular and mitochondrial ROS generation that leads to mitochondrial dysfunction. Furthermore, endoplasmic reticulum (ER) stress was triggered in PG-treated CR-SAS cells. The inhibition of ROS using Nacetylcysteine (NAC) abrogated the PG-induced ER stress and apoptosis, as well as the reduction in cell viability. Meanwhile, similar results were observed both in zebrafish and in murine models of drug-resistant oral cancer.
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