Ursolic acid derivative UA232 evokes apoptosis of lung cancer cells induced by endoplasmic reticulum stress

Autor: Na Luo, Ning Hongxin, Gou Wenfeng, Bi Changfen, Hongying Wu, Xiaojun Yu, Duan Yuqing, Yiliang Li, Huiqiang Wei, Wenbin Hou
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Lung Neoplasms
Time Factors
Pharmaceutical Science
Apoptosis
RM1-950
Pharmacology
030226 pharmacology & pharmacy
01 natural sciences
03 medical and health sciences
chemistry.chemical_compound
Broad spectrum
Inhibitory Concentration 50
0302 clinical medicine
Ursolic acid
Non-small cell lung cancer
Cell Line
Tumor
Drug Discovery
medicine
Humans
Lung cancer
Cell Proliferation
Natural product
Dose-Response Relationship
Drug
Chemistry
Endoplasmic reticulum
General Medicine
medicine.disease
Endoplasmic Reticulum Stress
Antineoplastic Agents
Phytogenic
Triterpenes
0104 chemical sciences
Bioavailability
respiratory tract diseases
010404 medicinal & biomolecular chemistry
Complementary and alternative medicine
A549 Cells
Molecular Medicine
Therapeutics. Pharmacology
Derivative (chemistry)
Research Article
Signal Transduction
Zdroj: Pharmaceutical Biology
article-version (VoR) Version of Record
Pharmaceutical Biology, Vol 58, Iss 1, Pp 707-715 (2020)
ISSN: 1744-5116
1388-0209
Popis: Context Ursolic acid (UA), a natural product, shows a broad spectrum of anticancer effects. However, the poor bioavailability and efficacy of UA limit its clinical application. Objective We developed novel analogues of UA with enhanced antitumor activities by the extensive chemical modification of UA. Materials and methods We developed multiple compounds by structural modification of UA, and found that UA232 had stronger activity than UA. The effects of UA232 (0–50 μM) on inhibiting the proliferation of A549 and H460 cells were determined by CCK-8 for 24, 48, or 72 h. The proapoptotic effect of UA232 was analyzed by microscopy and flow cytometry, and the potential signal pathway affected by UA232 was further validated by Western blotting and flow cytometry. Results Compared with UA, UA232 showed a stronger ability to inhibit the proliferation of lung cancer cells (IC50 = 5.4–6.1 μM for A549 and 3.9–5.7 μM for H460 cells). UA232 could induce not only cell cycle arrest in the G0/G1 phase but also apoptosis in both A549 and H460 cells. The treatment of UA232 could lead to an increase of CHOP expression rather than an increase in Bax or caspase-8, indicating that the apoptosis induced by UA232 was correlated with the endoplasmic reticulum stress (ER stress) pathway. Treatment with the ER stress-specific inhibitor, 4-PBA, decreased the ability of UA232 to induce apoptosis in A549 and H460 cells. Conclusion UA232 induced apoptosis through the ER stress pathway, and showed stronger growth-inhibitory effects in A549 and H460 cells compared to UA, which may be a potential anticancer drug to suppress the proliferation of lung cancer.
Databáze: OpenAIRE
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