Identification of Bulbocodin D and C as novel STAT3 inhibitors and their anticancer activities in lung cancer cells.
10.1016/S1875-5364(23)60521-7
- Author:
Xinyu HE
1
;
Jiarui FU
2
;
Wenyu LYU
1
;
Muyang HUANG
1
;
Jianshan MO
3
;
Yaxin CHENG
1
;
Yulian XU
4
;
Lijun ZHENG
5
;
Xiaolei ZHANG
3
;
Lu QI
6
;
Lele ZHANG
7
;
Ying ZHENG
1
;
Mingqing HUANG
8
;
Lin NI
9
;
Jinjian LU
10
,
11
,
12
Author Information
1. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China.
2. College of Plant Protection, Fujian Agriculture and Forestry University, Fuzhou 350002, China.
3. National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation, Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
4. College of Life Sciences, China Jiliang University, Hangzhou 310018, China.
5. Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou 350100, China.
6. Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
7. School of Basic Medical Sciences, Chengdu University, Chengdu 610106, China.
8. College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350003, China. Electronic address: hmq1115@126.com.
9. College of Plant Protection, Fujian Agriculture and Forestry University, Fuzhou 350002, China. Electronic address: nilin_fjau@126.com.
10. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China
11. Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Macao 999078, China
12. Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, University of Macau, Macao 999078, China. Electronic address: jinjianlu@um.edu.mo.
- Publication Type:Journal Article
- Keywords:
Bulbocodin C;
Bulbocodin D;
Cancer;
ERK;
Natural products;
STAT3
- MeSH:
Humans;
Lung Neoplasms/metabolism*;
STAT3 Transcription Factor/metabolism*;
Antineoplastic Agents/chemistry*;
A549 Cells;
Apoptosis;
Cell Line, Tumor;
Cell Proliferation
- From:
Chinese Journal of Natural Medicines (English Ed.)
2023;21(11):842-851
- CountryChina
- Language:English
-
Abstract:
Cancer stands as one of the predominant causes of mortality globally, necessitating ongoing efforts to develop innovative therapeutics. Historically, natural products have been foundational in the quest for anticancer agents. Bulbocodin D (BD) and Bulbocodin C (BC), two bibenzyls derived from Pleione bulbocodioides (Franch.) Rolfe, have demonstrated notable in vitro anticancer activity. In human lung cancer A549 cells, the IC50s for BD and BC were 11.63 and 11.71 μmol·L-1, respectively. BD triggered apoptosis, as evidenced by an upsurge in Annexin V-positive cells and elevated protein expression of cleaved-PARP in cancer cells. Furthermore, BD and BC markedly inhibited the migratory and invasive potentials of A549 cells. The altered genes identified through RNA-sequencing analysis were integrated into the CMap dataset, suggesting BD's role as a potential signal transducer and activator of transcription 3 (STAT3) inhibitor. SwissDock and MOE analyses further revealed that both BD and BC exhibited a commendable binding affinity with STAT3. Additionally, a surface plasmon resonance assay confirmed the direct binding affinity between these compounds and STAT3. Notably, treatment with either BD or BC led to a significant reduction in p-STAT3 (Tyr 705) protein levels, regardless of interleukin-6 stimulation in A549 cells. In addition, the extracellular signal-regulated kinase (ERK) was activated after BD or BC treatment. An enhancement in cancer cell mortality was observed upon combined treatment of BD and U0126, the MEK1/2 inhibitor. In conclusion, BD and BC emerge as promising novel STAT3 inhibitors with potential implications in cancer therapy.
