Andrographolide induces apoptotic and non‑apoptotic death and enhances tumor necrosis factor‑related apoptosis‑inducing ligand‑mediated apoptosis in gastric cancer cells

Lim,Sung‑Chul; Jeon,Ho Jong; Kee,Keun Hong; Lee,Mi Ja; Hong,Ran; Han,Song Iy

doi:10.3892/ol.2017.5923

Andrographolide induces apoptotic and non‑apoptotic death and enhances tumor necrosis factor‑related apoptosis‑inducing ligand‑mediated apoptosis in gastric cancer cells

Authors:
- Sung‑Chul Lim
- Ho Jong Jeon
- Keun Hong Kee
- Mi Ja Lee
- Ran Hong
- Song Iy Han
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Affiliations: Department of Pathology, College of Medicine, Chosun University, Gwangju 61452, Republic of Korea, Division of Premedical Science, College of Medicine, Chosun University, Gwangju 61452, Republic of Korea
Published online on: March 27, 2017 https://doi.org/10.3892/ol.2017.5923
Pages: 3837-3844

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Abstract

Andrographolide, a natural compound isolated from Andrographis paniculata, has been reported to possess antitumor activity. In the present study, the effect of andrographolide in human gastric cancer (GC) cells was investigated. Andrographolide induced cell death with apoptotic and non‑apoptotic features. At a low concentration, andrographolide potentiated apoptosis and reduction of clonogenicity triggered by recombinant human tumor necrosis factor‑related apoptosis‑inducing ligand (rhTRAIL). Exposure of GC cells to andrographolide altered the expression level of several growth‑inhibiting and apoptosis‑regulating proteins, including death receptors. It was demonstrated that activity of the TRAIL‑R2 (DR5) pathway was critical in the development of andrographolide‑mediated rhTRAIL sensitization, since its inhibition significantly reduced the extent of apoptosis induced by the combination of rhTRAIL and andrographolide. In addition, andrographolide increased reactive oxygen species (ROS) generation in a dose‑dependent manner. N‑acetyl cysteine prevented andrographolide‑mediated DR5 induction and the apoptotic effect induced by the combination of rhTRAIL and andrographolide. Collectively, the present study demonstrated that andrographolide enhances TRAIL‑induced apoptosis through induction of DR5 expression. This effect appears to involve ROS generation in GCs.

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