2. Academic Validation
  3. Auriculasin-induced ROS causes prostate cancer cell death via induction of apoptosis

Auriculasin-induced ROS causes prostate cancer cell death via induction of apoptosis

  • Food Chem Toxicol. 2018 Jan:111:660-669. doi: 10.1016/j.fct.2017.12.007.
Hyun-Dong Cho 1,  Ju-Hye Lee 2,  Kwang-Deog Moon 1,  Ki-Hun Park 3,  Mi-Kyung Lee 4,  Kwon-Il Seo 5
Affiliations

Affiliations

  • 1 Department of Food Science and Technology, Kyungpook National University, Daegu, 41566, Republic of Korea.
  • 2 Functional Food and Nutrition Division, Department of Agro-Food Resource, National Academy of Agricultural Science, Rural Development Administration, Wanju, 55365, Republic of Korea.
  • 3 Division of Applied Life Science (BK21 Plus), IALS, Gyeongsang National University, Jinju, 52828, Republic of Korea.
  • 4 Department of Food and Nutrition, Sunchon National University, Suncheon, 57922, Republic of Korea.
  • 5 Department of Biotechnology, Dong-A University, Busan, 49315, Republic of Korea. Electronic address: kseo@dau.ac.kr.
PMID: 29217266 DOI: 10.1016/j.fct.2017.12.007
Abstract

Recent studies have demonstrated that natural agents targeting the accumulation of Reactive Oxygen Species (ROS) that selectively kill, leaving normal cells undamaged, can suppress prostate Cancer. Here, we show that auriculasin, derived from Flemingia philippinensis, induces significant cell death and Apoptosis via ROS generation in prostate Cancer cells. Auriculasin treatment resulted in selective apoptotic cell death in LNCaP prostate Cancer cells, characterized by DNA fragmentation, accumulation of sub-G1 cell population, cleavage of poly (ADP-ribose) polymerase (PARP), regulation of Bax/Bcl-2 ratio, increase of cytosolic apoptosis-inducing factor (AIF) and Endonuclease G (EndoG), in addition to inhibiting tumor growth in a xenograft mouse model. Interestingly, auriculasin-induced Apoptosis did not result in Caspase-3, -8, and -9 activations. We found that auriculasin treatment decreased phosphorylation of Akt/mTOR/p70S6K in a dose- and time-dependent manner. Further, cellular ROS levels increased in LNCaP cells treated with auriculasin and blocking ROS accumulation with ROS scavengers resulted in inhibition of auriculasin-induced PARP cleavage, AIF increase, upregulation of Bax/Bcl-2 ratio, and decrease in Akt/mTOR phosphorylation. Taken together, these data suggest that auriculasin targets ROS-mediated caspase-independent pathways and suppresses PI3K/Akt/mTOR signaling, which leads to Apoptosis and decreased tumor growth.

Keywords

Apoptosis; Auriculasin; Prostate cancer; Reactive oxygen species.

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