Anthricin‑induced caspase‑dependent apoptosis through IGF1R/PI3K/AKT pathway inhibition in A549 human non‑small lung cancer cells

Park,Bo‑Ram; Lee,Seul Ah; Moon,Sung Min; Kim,Chun Sung

doi:10.3892/or.2018.6333

Anthricin‑induced caspase‑dependent apoptosis through IGF1R/PI3K/AKT pathway inhibition in A549 human non‑small lung cancer cells

Authors:
- Bo‑Ram Park
- Seul Ah Lee
- Sung Min Moon
- Chun Sung Kim
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Affiliations: Department of Dental Hygiene, Chodang University, Muan‑ro, Muan‑eup, Muan 534‑701, Republic of Korea, Department of Oral Biochemistry, College of Dentistry, Chosun University, Dong‑gu, Gwangju 501‑759, Republic of Korea, CStech Research Institute, Gwangju 61007, Republic of Korea
Published online on: March 27, 2018 https://doi.org/10.3892/or.2018.6333
Pages: 2769-2776

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Abstract

Anthricin (deoxypodophyllotoxin) is a major lignan in Anthriscus sylvestris and possesses many bioactivities such as antiproliferative, antitumor, anti‑platelet aggregation, antiviral and anti‑inflammatory actions. However, the anticancer effects of anthricin on A549 human non‑small cell lung cancer cells and potential molecular mechanisms remain unknown. Therefore, we investigated the anticancer effect of anthricin and the underlying mechanism in A549 cells. Anthricin (10‑200 nM) inhibited the viability of A549 cells in a dose‑ and time‑dependent manner. Moreover, anthricin‑induced apoptosis was confirmed by live and dead assay, 4,6‑dianmidino‑2‑phenylindole staining, and flow cytometric analysis. In addition, anthricin induced cell cycle arrest at the G2/M phase through suppression of the expression of cell cycle cascade proteins, Cdc2 and Cdc25C. Furthermore, it induced the expression of caspase‑related proteins and significantly suppressed the phosphorylation of insulin‑like growth factor 1 receptor (IGF1R), PI3K and Akt. Anthricin significantly inhibited tumor growth without any significant change in the body weight of mice in A549 tumor xenograft BALB/c nude mice. Anthricin induced caspase‑dependent apoptosis through the IGF1R/PI3K/Akt signaling pathway in A549 cells.

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