Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Osthole represses growth of multiple myeloma cells by regulating PI3K/AKT and ERK pathways

Lingling Huang^1,2, Xiaofeng Zhao², Zhengmei He³, Lizhong Guo¹

¹First Clinical Medical College of Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing City, Jiangsu Province 210046; ²Department of Chinese Medicine, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an City, Jiangsu Province 223300; ³Department of Hematology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an City, Jiangsu Province 223300, China.

For correspondence:- Lizhong Guo Email: LizhongGuo431@163.com Tel:+8651780872635

Accepted: 26 October 2019 Published: 30 November 2019

Citation: Huang L, Zhao X, He Z, Guo L. Osthole represses growth of multiple myeloma cells by regulating PI3K/AKT and ERK pathways. Trop J Pharm Res 2019; 18(11):2287-2292 doi: 10.4314/tjpr.v18i11.8

© 2019 The authors.
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Abstract

Purpose: To identify the effects of osthole on the growth of multiple myeloma cells and determine the probable molecular mechanism of action.

Methods: 3-(4, 5-Dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay was used to measure multiple myeloma cell viability. Flow cytometry was used for the evaluation of cell cycle and apoptosis. For protein expression measurement, western blot analysis was employed.

Results: The results show that osthole dose- and time-dependently suppressed the viability of multiple myeloma cells (p < 0.01). Osthole also dose-dependently initiated multiple myeloma cell cycle arrest in G0/G1 phase (p < 0.05) and induced multiple myeloma cell apoptosis (p < 0.01). Moreover, western blotting revealed a significant reduction in cyclin D1 (p < 0.01) and induction in p21, cleaved caspase 3 and cleaved poly (ADP-ribose) polymerase (p < 0.01). Furthermore, osthole treatment significantly downregulated the phosphorylation levels of protein kinase B (AKTT308), AKTS473, and extracellular regulated protein kinase 1/2 (ERK1/2).

Conclusion: These findings demonstrated that osthole inhibited viability and induced cell cycle arrest and apoptosis of multiple myeloma cells by regulating PI3K/AKT and ERK pathways. Osthole may be considered as a potential anticancer agent for the therapy of multiple myeloma.

Keywords: Multiple myeloma, Osthole, Phosphatidylinositol 3 kinase, Protein kinase B, Extracellular regulated protein kinases, Cell growth