Phenolic alkaloids from Menispermum dauricum inhibits BxPC-3 pancreatic cancer cells by blocking of Hedgehog signaling pathway

Zhong-guang Zhou; Chao-ying Zhang; Hong-xin Fei; Li-li Zhong; Yun Bai

Articles

Abstract

Pharmacognosy Magazine,2015,11,44,690-697.

DOI:10.4103/0973-1296.165548

Published:September 2015

Type:Original Article

Authors:

Author(s) affiliations:

Zhong-guang Zhou¹, Chao-ying Zhang², Hong-xin Fei³, Li-li Zhong⁴, Yun Bai⁵
¹ Research Institute of Traditional Chinese Medicine, Heilongjiang University of Chinese Medicine, Heilongjiang, China
² The Fourth Affiliated Hospital, Harbin Medical University, Heilongjiang, China
³ Research Institute of Traditional Chinese Medicine, Heilongjiang University of Chinese Medicine; Department of Qiqihar Medical University, Basic Medicine, Heilongjiang, China
⁴ Department of Pathology, The First Affiliated Hospital, Heilongjiang, China
⁵ Basic Medical College, Heilongjiang University of Chinese Medicine, Heilongjiang, China

Abstract:

Background: The Hedgehog (Hh) signaling pathway plays an important role in pancreatic cancer (PC) cells. Phenolic alkaloids from Menispermum dauricum (PAMD), a traditional Chinese medicine used for the treatment of immune disorders, have been reported to have antitumor activity recently. Objective: To investigate the efficacy and mechanism of PAMD against PC cell BxPC-3. Materials and Methods: F assay was used to assess cell proliferation inhibition of PAMD; the apoptotic induction and cell cycle arrest was detected by flow cytometry; the BxPC-3 xenograft was established to evaluate the tumor growth inhibition of PAMD; hematoxylin-eosin staining was applied to analyze the pathological morphology of tumor tissues; immunohistochemistry (IHC) and Western blot was adopted to detect the protein levels; quantitative real-time polymerase chain reaction was used to determine the mRNA expressions. Results: PAMD shows time-and dose-dependent proliferation inhibition on the BxPC-3 cell, induced G0/G1 phase arrest and cell apoptosis in vitro. PAMD also showed better inhibition of tumor growth and a preferable safety profile compared with chemotherapeutic regimen 5-fluoro-2, 4 (1 H, 3 H) pyrimidinedione in BxPC-3 xenograft in vivo. Furthermore, PAMD directly decreases the protein and mRNA levels of Sonic Hedgehog (Shh) and its downstream transcription factor Gli-1 in the BxPC-3 tumor tissues. Conclusion: The treatment of PAMD displayed Hh signaling pathway blockade through decreasing the protein and mRNA levels of Shh and its downstream transcription factor Gli-1, suggesting a promising strategy in treating human PC.