Cancer Management and Research (Jul 2020)
Honokiol Suppressed Pancreatic Cancer Progression via miR-101/Mcl-1 Axis
Abstract
Yishuo Wang,1,2 Zhongyong Liu,1,2 Qinrong Liu,1,2 Yongguang Han,1,2 Yuncai Zang,1,2 Huichao Zhang,1,2 Xuzhao Du,1,2 Tao Qin,3 Yuquan Wu1,2 1College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 2Henan Integrated Engineering Technology Research Center of Traditional Chinese Medicine Production, Zhengzhou, People’s Republic of China; 3Department of Rheumatology, Xinmi Hospital of Traditional Chinese Medicine, Xinmi, People’s Republic of ChinaCorrespondence: Yishuo WangCollege of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, People’s Republic of ChinaTel +86-13619847844Email [email protected]: Pancreatic cancer is one of the most aggressive malignancies. The present study aimed to examine the anti-tumor effects of honokiol in pancreatic cancer and to explore the underlying molecular mechanisms.Materials and Methods: In vitro functional assays determined pancreatic cancer cell proliferation, apoptosis and invasion. Xenograft nude mice model determined the in vivo anti-cancer effects of honokiol. Luciferase reporter assay determined the interaction between miR101 and myeloid cell leukemia-1 (Mcl-1).Results: Honokiol concentration-dependently suppressed pancreatic cancer cell viability. In addition, honokiol increased the caspase-3 activity and cell apoptotic rates, induced cell cycle arrest at G0/G1 phase, and inhibited cell invasion in pancreatic cancer. Interestingly, honokiol treatment induced up-regulation of miR-101 in pancreatic cancer cells. Knockdown of miR-101 attenuated the honokiol-induced cell apoptosis and inhibition in cell invasion of pancreatic cancer cells. On the other hand, miR-101 overexpression induced cell apoptosis and inhibited cell viability and invasion in pancreatic cancer. Further mechanistic study verified that Mcl-1 was negatively regulated by miR-101, and Mcl-1 overexpression counteracted the tumor-suppressive effects of honokiol on the pancreatic cancer cells. In vivo studies showed that honokiol dose-dependently suppressed tumor growth of pancreatic cancer in the nude mice and up-regulated miR-101 expression but down-regulated Mcl-1 expression in tumor tissues.Conclusion: Our data showed that honokiol suppressed pancreatic cancer progression via miR-101-Mcl-1 axis. Honokiol could be a promising candidate for cancer prevention and/or therapeutic treatment for pancreatic cancer.Keywords: pancreatic cancer, honokiol, miR-101, apoptosis, invasion, Mcl-1
