Flavonoids isolated from Citrus platymamma induced G2/M cell cycle arrest and apoptosis in A549 human lung cancer cells

Nagappan,Arulkumar; Lee,Ho  Jeong; Saralamma,Venu   Venkatarame Gowda; Park,Hyeon  Soo; Hong,Gyeong  Eun; Yumnam,Silvia; Raha,Suchismita; Charles,Shobana  Nancy; Shin,Sung  Chul; Kim,Eun  Hee; Lee,Won  Sup; Kim,Gon  Sup

doi:10.3892/ol.2016.4793

Flavonoids isolated from Citrus platymamma induced G2/M cell cycle arrest and apoptosis in A549 human lung cancer cells

Authors:
- Arulkumar Nagappan
- Ho Jeong Lee
- Venu Venkatarame Gowda Saralamma
- Hyeon Soo Park
- Gyeong Eun Hong
- Silvia Yumnam
- Suchismita Raha
- Shobana Nancy Charles
- Sung Chul Shin
- Eun Hee Kim
- Won Sup Lee
- Gon Sup Kim
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Affiliations: Department of Internal Medicine, Institute of Health Sciences and Gyeongnam Regional Cancer Center, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam 660‑702, Republic of Korea, Brain Korea 21 Program for Leading Universities and Students, Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Jinju, Gyeongnam 660‑701, Republic of Korea, Department of Chemistry, Research Institute of Life Science, Gyeongsang National University, Jinju, Gyeongnam 660‑701, Republic of Korea, Department of Nursing Science, International University of Korea, Jinju, Gyeongnam 660‑759, Republic of Korea
Published online on: June 28, 2016 https://doi.org/10.3892/ol.2016.4793
Pages: 1394-1402
Copyright: © Nagappan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Citrus platymamma hort. ex Tanaka belongs to the Rutaceae family and is widely used in folk medicines in Korea due to its anti‑proliferative, anti‑cancer, anti‑oxidant, anti‑inflammatory and anti‑diabetic activities. However, the molecular mechanism of its anti‑cancer effect is not well understood. The present study was conducted to elucidate the anti‑cancer effect and molecular mechanism of flavonoids from Citrus platymamma (FCP) on A549 cells. FCP displayed concentration-dependent inhibition on A549 cells proliferation. Further, flow cytometry revealed that FCP significantly increased the sub‑G1 (apoptotic cell population) and G2/M phase population, and the total number of apoptotic cells, in a dose‑dependent manner. Nuclear condensation and fragmentation were also observed upon staining with Hoechst 33342 in FCP‑treated A549 cells. Immunoblotting demonstrated a dose‑dependent downregulation of cyclin B1, cyclin‑dependent kinase 1, cell division cycle 25c, pro‑caspases ‑3, ‑6, ‑8 and ‑9, and poly (adenosine diphosphate‑ribose) polymerase (PARP) in FCP‑treated A549 cells. In addition, FCP induced caspase‑3 activation and subsequent PARP cleavage, and increased the B‑cell lymphoma (Bcl)‑2‑associated X protein/Bcl‑extra large ratio in A549 cells. These findings suggest that FCP induced G2/M arrest and apoptosis of A549 cells. The present study provides evidence that FCP may be useful in the treatment of human lung cancer.

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