Aging
Navigate
Submit an Article
Research Paper|Volume 12, Issue 1|pp 138—155

Lycorine induces autophagy-associated apoptosis by targeting MEK2 and enhances vemurafenib activity in colorectal cancer

Man Hu1, Zhaomin Yu1, Peiyuan Mei2, Jinxiao Li1, Dan Luo3, Haiming Zhang4, Minfeng Zhou5, Fengxia Liang5, Rui Chen1
  • 1Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  • 2Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  • 3Department of Respiratory Medicine, Wuhan First Hospital, Wuhan, China
  • 4Department of Oncology, Integrated Traditional Chinese and Western Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  • 5Department of Acupuncture, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China
Received: June 11, 2019Accepted: December 5, 2019Published: January 3, 2020
https://doi.org/10.18632/aging.102606

Copyright: © 2020 Hu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Lycorine is a powerful anti-cancer agent against various cancer cell lines with minor side effects. However, the detailed mechanisms of its effects in colorectal cancer (CRC) remain unclear. In this study, we investigated the function and mechanism of lycorine against CRC both in vitro and in vivo. Molecular docking modeling was used to identify potential inhibitory targets of lycorine in CRC. Cell viability was measured using the Cell Counting Kit-8 assay, and apoptosis was measured using flow cytometry. Autophagosomes were examined using transmission electron microscopy and confocal microscopy. HCT116-derived xenografts were constructed to analyze the effect of lycorine in CRC in vivo. Using the CDOCKER algorithm, we determined that lycorine has four interactions with the conserved domain of mitogen-activated protein kinase kinase 2 (MEK2). This prediction was further confirmed by the degradation of phosphorylated MEK2 and its downstream targets after lycorine treatment, and MEK2 overexpression abolished lycorine-induced autophagy-associated apoptosis. Additionally, we revealed that the combination of vemurafenib and lycorine had better effects in CRC models in vitro and in vivo than monotherapy. Our findings identified lycorine as an effective MEK2 inhibitor and suggested that the combination of lycorine and vemurafenib could be used to treat CRC.