Flavokawains A and B from kava (Piper methysticum) activate heat shock and antioxidant responses and protect against hydrogen peroxide-induced cell death in HepG2 hepatocytes.

Authors:
Keanu D Pinner
Keanu D Pinner
Daniel K. Inouye College of Pharmacy
Rachel A Gristock
Rachel A Gristock
Daniel K. Inouye College of Pharmacy
Hoa T Vo
Hoa T Vo
a Mountain Manor Treatment Center
Nadine So
Nadine So
Daniel K. Inouye College of Pharmacy
Aaron T Jacobs
Aaron T Jacobs
Vanderbilt Institute of Chemical Biology
United States

Pharm Biol 2016 Sep 20;54(9):1503-12. Epub 2016 Jan 20.

a Department of Pharmaceutical Sciences , Daniel K. Inouye College of Pharmacy, University of Hawaii at Hilo , Hilo , HI , USA ;

Context Flavokawains are secondary metabolites from the kava plant (Piper methysticum Forst. f., Piperaceae) that have anticancer properties and demonstrated oral efficacy in murine cancer models. However, flavokawains also have suspected roles in rare cases of kava-induced hepatotoxicity. Objective To compare the toxicity flavokawains A and B (FKA, FKB) and monitor the resulting transcriptional responses and cellular adaptation in the human hepatocyte cell line, HepG2. Materials and methods HepG2 were treated with 2-100 μM FKA or FKB for 24-48 h. Cellular viability was measured with calcein-AM and changes in signalling and gene expression were monitored by luciferase reporter assay, real-time PCR and Western blot of both total and nuclear protein extracts. To test for subsequent resistance to oxidative stress, cells were pretreated with 50 μM FKA, 10 μM FKB or 10 μM sulphoraphane (SFN) for 24 h, followed by 0.4-2.8 mM H2O2 for 48 h, and then viability was assessed. Results FKA (≤100 μM) was not toxic to HepG2, whereas FKB caused significant cell death (IC50=23.2 ± 0.8 μM). Both flavokawains activated Nrf2, increasing HMOX1 and GCLC expression and enhancing total glutathione levels over 2-fold (p < 0.05). FKA and FKB also activated HSF1, increasing HSPA1A and DNAJA4 expression. Also, flavokawain pretreatment mitigated cell death after a subsequent challenge with H2O2, with FKA being more effective than FKB, and similar to SFN. Conclusions Flavokawains promote an adaptive cellular response that protects hepatocytes against oxidative stress. We propose that FKA has potential as a chemopreventative or chemotherapeutic agent.

Download full-text PDF

Source
http://dx.doi.org/10.3109/13880209.2015.1107104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5040346PMC

Still can't find the full text of the article?

We can help you send a request to the authors directly.
September 2016
322 Reads

Publication Analysis

Top Keywords

piper methysticum
8
fka fkb
8
cell death
8
flavokawains
5
responses cellular
4
transcriptional responses
4
monitor transcriptional
4
fka ≤100 μm
4
fkb monitor
4
total nuclear
4
cellular adaptation
4
hepatocyte cell
4
cell hepg2
4
human hepatocyte
4
50 μm fka
4
viability assessed
4
adaptation human
4
assessed fka
4
fkb
4
hepg2 fkb
4

Similar Publications