Theaflavine-3,3\'-digallate br Joseph L Kelly Contribute
Joseph L. Kelly: Contributed to the collection of study data, revision of the article, and approved the final version submitted for publication.
Kirsten Moysich: Contributed to the collection of study data, concep-tion and design of the study, revision of the article, and approved the final version submitted for publication.
Roberta B. Ness, MD: Contributed to the collection of study data, con-ception and design of the study, revision of the article, and approved the final version submitted for publication.
Maria Mori Brooks: Contributed to the analysis and interpretation of data, revision of the article, and approved the final version submitted for publication.
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://doi.
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Biomedicine & Pharmacotherapy
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Bruceine D induces apoptosis in human non-small cell lung cancer Theaflavine-3,3\'-digallate through regulating JNK pathway
Biqin Tana, Yuyu Huanga, Lihua Lanb, Bo Zhanga, Lijun Yea, Wei Yana, Fei Wanga, , Nengming Lina,
a Department of Clinical Pharmacology, Aﬃliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310006, China
b Institute of Agricultural Bio-Environmental Engineering, College of Biosystem Engineering and Food Science, Zhejiang University, Hangzhou, Zhejiang, 310058, China
Non-small cell lung cancer
Bruceine D (BD) is the quassinoids isolated from the traditional Chinese herbal medicine Brucea javanica’s fruit, which exhibits anti-cancer activity. Here, we demonstrated that BD inhibited human non-small cell lung cancer (NSCLC) cell lines in vitro that were attributed to the induction of cell apoptosis. Human NSCLC H460 and A549 cell lines were treated with BD, and cell viability was conducted with CCK-8 assay. Cell clone formation was observed by clone formation assay. Cell apoptosis was measured using DAPI staining and flow cytometry. Protein levels was analyzed by western blot. The results showed BD inhibited the cell viability of H460 and A549 cells in a dose-dependent manner with IC50 values of 0.5 and 0.6 μmol/L, respectively, at 48 h of treatment. Treatment with BD (0.125–1.0 μmol/L) dose-dependently promoted chromatin condensation, Annexin V-posi-tive cell population and caspase-dependent apoptosis in H460 and A549 cells. Mechanistically, BD stimulated the phosphorylation of JNK. Furthermore, the anti-cancer eﬀects of BD were alleviated eﬀectively by a specific JNK inhibitor SP600125 in NSCLC cells. In conclusion, the results demonstrated that BD exerted anti-cancer activity against NSCLC cells through JNK activation, which suggests its potent usefulness for prevention and treatment of NSCLC.
Lung cancer is the leading cause of cancer death and the most commonly diagnosed cancer, with 1.8 million new cases and 1.6 million deaths each year [1–3]. Approximately 85%–90% of all lung cancers are classified as Non-small cell lung cancer (NSCLC) [4,5]. Most NSCLC patients are diagnosed at terminal stage that surgery is not suitable for them, so chemotherapy has the mainstay of treatment for patients with advanced NSCLC . Platinum-based chemotherapy, the standardized treatment for all patients with incurable locally advanced or metastatic NSCLC, has produced only a response rate of 19% and 5-year overall survival (OS) of less than 15% [7,8]. Given that dismal data, it em-phasizes an urgent need for new therapeutic agents with high eﬃciency for this deadly disease.
Natural products are important source of anti-tumor chemicals. Recent years, a number of natural compounds have been reported to exhibit eﬃcient anti-tumor activity, such as curcumin, emodin, silybin [9–13]. Previous study indicated that the fruit of a traditional Chinese medicine Brucea javanica (L.) Merr (Simaroubaceae) could inhibit pancreatic cancer cell proliferation and induce apoptosis in vitro .
Furthermore, it was revealed that quassinoids as the characteristic secondary metabolites of B. javanica acted eﬀectively against cancer cells . Bruceine D (BD), as one of the quassinoids isolated from B. javanica’s fruit, exhibited cytotoxic eﬀect on pancreatic adenocarci-noma cells [16–18]. However, the cytotoxicity of BD in NSCLC remains unclarified.