Abstract
BackgroundPhysalin A isolated from Physalis alkekengi var. franchetii has been known to have many pharmacological properties. However, its effect through the Nrf2 pathway has not yet been elucidated. In the present study, we determined the effects of physalin A on cancer chemoprevention via the Nrf2 pathway.MethodsExperiments were performed in Hepa-1c1c7 and HepG2 cells. The quinone reductase (QR) activity assay was used to assess the activity of physalin A and other compounds isolated from P. alkekengi. The antioxidant response element (ARE) reporter assay was used to determine physalin A induced transcription of Nrf2 target genes, whereas the oligonucleotide pull-down assay was used to investigate Nrf2 binding to the AREs post physalin A treatment. Real-time PCR and western blotting were performed to determine the expression of Nrf2 target genes. Immunocytochemistry was used to determine Nrf2 localization after treatment with physalin A. Kinase inhibitors were used to test the involvement of Nrf2-targeting kinases and the role of ERK and p38 phosphorylation was confirmed using western blotting.ResultsPhysalin A significantly induced QR activity. As an upstream effector of QR, Nrf2 induced genes containing the ARE, which encode various antioxidants and detoxification enzymes. We observed that physalin A increased the expression of Nrf2 and its target genes in HepG2 cells. Moreover, we observed that physalin A-induced Nrf2 activation was regulated by ERK and p38 kinase in HepG2 cells.ConclusionsTaken together, we showed that physalin A increased detoxifying enzyme expression via activation of Nrf2 and its target genes. These results imply that physalin A could be a potential chemopreventive agent for liver diseases, as well as cancer.
Highlights
Physalin A isolated from Physalis alkekengi var. franchetii has been known to have many pharmacological properties
We investigated the effect of P. alkekengi and physalin A on cancer chemoprevention via the Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway
Sulforaphane was used as a positive control in these experiments. These results showed that physalin A is an active component responsible for induction of quinone reductase (QR) activity
Summary
Physalin A isolated from Physalis alkekengi var. franchetii has been known to have many pharmacological properties. Its effect through the Nrf pathway has not yet been elucidated. We determined the effects of physalin A on cancer chemoprevention via the Nrf pathway. The fifth-most common cancer worldwide, is the third-most common cause of mortality due to cancer [1]. Liver cancer-associated mortality in both men and women is higher than the diagnostic rates [2]. Prevention of liver cancer is of utmost importance. Synthetic or natural pharmaceutical agents mainly used, especially, traditional medicine is useful to prevent the Phytochemicals, especially plant-derived compounds, are used in clinical trials as cancer chemopreventive agents [6]. Sulforaphane is a representative phytochemical obtained by hydrolysis of glucoraphanin, which is abundant in broccoli. Sulforaphane inhibits cancer growth and the overall carcinogenetic process by inducing phase II enzymes, including quinone reductase (QR, NAD(P)H: quinone oxidoreductase) and glutathione S-transferases (GSTs) [6, 7]
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