Neferine from Nelumbo nucifera induces autophagy through the inhibition of PI3K/Akt/mTOR pathway and ROS hyper generation in A549 cells

• Published in: Food chemistry 2013-12, Vol.141 (4), p.3598-3605
• Main Authors: Poornima, Paramasivan, Weng, Ching Feng, Padma, Viswanadha Vijaya
• Format: Article
• Language: English
• Subjects: Apoptosis - drug effects; Autophagy; Autophagy - drug effects; Benzylisoquinolines - pharmacology; Biological and medical sciences; Cell Line, Tumor; Down-Regulation - drug effects; Food toxicology; GSH; Humans; Medical sciences; mTOR; Neferine; Nelumbo - chemistry; Neoplasms - metabolism; Neoplasms - physiopathology; Phosphatidylinositol 3-Kinases - metabolism; Plant Extracts - pharmacology; Proto-Oncogene Proteins c-akt - metabolism; Reactive Oxygen Species - metabolism; ROS; Signal Transduction - drug effects; TOR Serine-Threonine Kinases - metabolism; Toxicology
• ISSN: 0308-8146; 1873-7072
• DOI: 10.1016/j.foodchem.2013.05.138

•We examine the antiproliferative effect of neferine on lung cancer cells.•Neferine exerts cytotoxicity in a dose dependent manner.•ROS hypergeneration and GSH depletion was induced by neferine in A549 cells.•Neferine induces PI3K/Akt/mTOR pathway dependent autophagy.•Supplementation of neferine may offer protection against lung cancer. Previously we have reported that neferine from the medicinal plant Nelumbo nucifera, inhibited cancer cell proliferation by inducing apoptosis. The present study was focused on the action mechanism of neferine in inducing autophagy in lung cancer cells. Neferine markedly inhibited A549 cell proliferation in a dose dependent manner. Acidic vesicular accumulation was observed in neferine treated cells as an indication of autophagy. Neferine could induce the conversion of LC3B-I to LC3B-II without affecting the expression levels of PI3KCIII and Beclin1. It has been observed that neferine mediated autophagy is dependent on inhibition of PI3K/Akt/mTOR signaling by neferine. Neferine treatment could also lead to the ROS hypergeneration and depletion of cellular antioxidant, GSH. The results demonstrate that neferine-induced autophagy is mediated through ROS hypergeneration and mTOR inhibition. Taken together, the present study unveils a novel mechanism of action of neferine on lung cancer cells in the induction of autophagy.