Anticancer activities of chalcone flavokawain B from Alpinia pricei Hayata in human lung adenocarcinoma (A549) cells via induction of reactive oxygen species-mediated apoptotic and autophagic cell death

You Cheng Hseu, Yu Chi Huang, Varadharajan Thiyagarajan, Dony Chacko Mathew, Kai Yuan Lin, Ssu Ching Chen, Jer Yuh Liu, Li Sung Hsu, Mei Ling Li, Hsin Ling Yang

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Chalcones found in fruits and vegetables have promising cancer chemopreventive properties. This study attempts to identify the anticancer efficacies of chalcone flavokawain B (FKB) in the rhizomes of Alpinia pricei Hayata by examining key molecular events in non-small-cell lung cancer (A549) cells. Our results indicated that in human A549 cells, FKB (0–15 μg/ml) decreases cell viability and colony formation, dysregulates the Bax:B-cell lymphoma 2 ratio and increases apoptotic DNA fragmentation. Mitochondrial (caspase-9/-3 and poly ADP ribose polymerase [PARP]) signaling was found to be involved in FKB-induced apoptosis. In addition, FKB-induced reactive oxygen species (ROS) generation, and N-acetylcysteine attenuated FKB-induced apoptotic cell death. Moreover, FKB triggered autophagy, as evidenced by the improved acidic vesicular organelle formation, lipidated light chain 3 (microtubule-related light chain 3) accumulation, and ATG7 expression and the decreased mammalian target of rapamycin phosphorylation. Furthermore, FKB suppressed ROS-mediated ATG4B expression. Inhibiting autophagy using 3-methyladenine/chloroquine diminished FKB-induced cell death, indicating that autophagy is triggered as a death mechanism by FKB. In summary, FKB has a crucial role in the execution and propagation of ROS-mediated apoptotic and autophagic cell death of lung adenocarcinoma cells.

Original languageEnglish
Pages (from-to)17514-17526
Number of pages13
JournalJournal of Cellular Physiology
Volume234
Issue number10
DOIs
StatePublished - Oct 2019

Keywords

  • Alpinia pricei hayata
  • apoptosis
  • autophagy
  • chalcone flavokawain B
  • ROS

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