Abstract
BackgroundPachymic acid (PA), a lanostane-type triterpenoid from Poria cocos, has been reported to possess anti-emetic, anti-inflammatory, and anti-cancer properties. Nonetheless, the anti-tumor effect of PA in lung cancer cells remains unclear. Herein, we report the chemotherapeutic effects and underlying mechanisms of PA against human lung cancer.MethodsThe anti-proliferative ability of PA on lung cancer cells was assessed by MTT, colony formation and EdU proliferation assays. Flow cytometric analysis was used to detect cell cycle changes. Apoptosis was determined by annexin V/PI double-staining and the DNA ladder formation assays. The expressions of the apoptosis-related proteins were analysed by western blot. The in vivo efficacy of PA was measured using a NCI-H23 xenograft model in nude mice.ResultsPA exhibited anti-tumor effects in vitro accompanied by induction of G2/M phase arrest and apoptosis in NCI-H23 and NCI-H460 lung cancer cells. Mechanistically, our data showed that PA induced reactive oxygen species (ROS) production, resulting in the activation of both c-Jun N-terminal kinase (JNK) and endoplasmic reticulum (ER) stress apoptotic pathways in lung cancer cells. Moreover, blockage of ROS production reversed PA-induced JNK and ER stress activation. Finally, PA inhibited the growth of NCI-H23 xenograft tumors without causing any host toxicity, and inhibited cell proliferation and induction of apoptosis of tumor cells in tumor xenograft tissues.ConclusionsIn summary, our study demonstrates that PA induces apoptosis through activation of the JNK and ER stress pathways in human lung cancer cells. Our findings provide a rationale for the potential application of PA in lung cancer therapy.
Highlights
Pachymic acid (PA), a lanostane-type triterpenoid from Poria cocos, has been reported to possess antiemetic, anti-inflammatory, and anti-cancer properties
We demonstrated that PA induced G2/M phase arrest and cell apoptosis in lung cancer cells, via activating reactive oxygen species (ROS)-dependent Jun N-terminal kinase (JNK) mitochondrial and endoplasmic reticulum (ER) stress pathways
Pachymic acid (PA) inhibits growth of human lung cancer cells in vitro To explore the biological role of PA in lung cancer, we first performed a cell viability assay on NCI-H23 and NCI-H460 cells by MTT assay, treated with different concentrations of PA (0, 20, 40, 80 and 160 μM) for 24, 48 and 72 h
Summary
Pachymic acid (PA), a lanostane-type triterpenoid from Poria cocos, has been reported to possess antiemetic, anti-inflammatory, and anti-cancer properties. The anti-tumor effect of PA in lung cancer cells remains unclear. We report the chemotherapeutic effects and underlying mechanisms of PA against human lung cancer. Many factors, including tobacco smoke, ionizing radiation and viral infection are known to increase the risk of NSCLC, the mechanisms involved in NSCLC formation remain largely unknown [2]. Despite improvements in tumor response to chemotherapy, the long-term survival rate for advanced lung cancer patients remains quite low [1], calling for a dire need of novel strategies to treat lung cancer with more active agents [3]. Herbal medicines have long been an important source for anti-cancer agents, and some of them are currently used in clinical practice [4]. A variety of FDA approved anti-tumor agents, including docetaxel and topotecan, have demonstrated clinical utility based on ongoing investigations of natural products
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