Bavachinin exhibits antitumor activity against non‑small cell lung cancer by targeting PPARγ

Ge,Lu‑Na; Yan,Lei; Li,Cheng; Cheng,Kai

doi:10.3892/mmr.2019.10485

Bavachinin exhibits antitumor activity against non‑small cell lung cancer by targeting PPARγ

Authors:
- Lu‑Na Ge
- Lei Yan
- Cheng Li
- Kai Cheng
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Affiliations: Shandong Medicinal Biotechnology Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250062, P.R. China, Department of Chemotherapy, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, Shandong 250117, P.R. China
Published online on: July 11, 2019 https://doi.org/10.3892/mmr.2019.10485
Pages: 2805-2811
Copyright: © Ge et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Bavachinin (BNN), one of the main active ingredients of Psoraleacorylifolia, can activate peroxisome proliferator‑activated receptor γ (PPARγ). PPARγ has become a promising therapeutic target in cancer. The aim of the present study was to explore the antitumor effects of BNN in non‑small cell lung cancer (NSCLC). Cell Counting Kit‑8 and lactate dehydrogenase release assays were performed to measure cell toxicity. Western blotting and immunofluorescence were used to analyze the expression of apoptosis‑related factors and PPARγ. The ability of PPARγ to bind to BNN was evaluated by drug affinity responsive target stability (DARTS) and cellular thermal shift assay (CETSA). A reactive oxygen species (ROS) assay kit was used to detect the ROS level. The results revealed that the survival rates and cell viability of A549 cells were reduced by BNN in a dose‑dependent manner. The present results also demonstrated that BNN dose‑dependently changed the expression of Bcl‑2, Bax, caspases‑3/9 and PPARγ. In addition, through the cytotoxic and anti‑proliferative effects, the apoptosis‑related proteins' inhibitive properties of BNN were completely inhibited by the PPARγ antagonists T0070907 and GW9662. The DARTS and CETSA results confirmed the protein binding activity of PPARγ. Furthermore, it was demonstrated that the BNN‑induced ROS generation was dependent on PPARγ activation. Taken together, the present study demonstrated that BNN induced the death of A549 cells by activating PPARγ, an effect mediated by the increased ROS level. These results highlighted the potential role of BNN as a chemotherapeutic agent against NSCLC.

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