Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Research Article

The Green Walnut Husks Induces Apoptosis of Colorectal Cancer through Regulating NLRC3/PI3K Pathway

Author(s): Chao Chen, Na An, Defeng Pang, Yuanyuan Cheng, Yingjie Chen, Xuefei Feng, Haoqi Lei, Wenqian He, Baofeng Yang, Yan Zhang* and Xin Zhao*

Volume 29, Issue 12, 2023

Published on: 17 April, 2023

Page: [940 - 946] Pages: 7

DOI: 10.2174/1381612829666230330105320

Price: $65

Abstract

Background: Colorectal cancer (CRC) is the most common type of gastrointestinal tumor, but the available pharmacological treatment is insufficient. As a traditional Chinese medicine, the green walnut husks (QLY) exhibit anti-inflammatory, analgesic, anti-bacterial and anti-tumor effects. However, the effects and molecular mechanisms of QLY extracts on CRC were not yet made known.

Objective: This study aims to provide efficient and low toxicity drugs for the treatment of CRC. The purpose of this study is to explore the anti-CRC effect and mechanism of QLY, providing preliminary data support for clinical research of QLY.

Methods: Western blotting, Flow cytometry, immunofluorescence, Transwell, MTT, Cell proliferation assay, and xenograft model were used to perform the research.

Results: In this study, the potential of QLY to inhibit the proliferation, migration invasion and induce apoptosis of the mouse colorectal cancer cell line CT26 in vitro was identified. The xenograft tumor model of CRC noted that QLY suppressed tumor growth without sacrificing body weight in mice. In addition, QLY-induced apoptosis in tumor cells through NLRC3/PI3K/AKT signaling pathway was revealed.

Conclusion: QLY regulates the levels of mTOR, Bcl-2 and Bax by affecting the NLRC3/PI3K/AKT pathway to promote apoptosis of tumor cells, suppressing cell proliferation, invasion and migration, and subsequently preventing the progression of colon cancer.

[1]
Zheng R, Zhang S, Zeng H, et al. Cancer incidence and mortality in China, 2016. J Natl Cancer center 2022; 2(1): 1-9.
[2]
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin 2022; 72(1): 7-33.
[http://dx.doi.org/10.3322/caac.21708] [PMID: 35020204]
[3]
Miller KD, Nogueira L, Mariotto AB, et al. Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin 2019; 69(5): 363-85.
[http://dx.doi.org/10.3322/caac.21565] [PMID: 31184787]
[4]
Zhan M, Zhang Y. Research progress on chemical constituents and pharmacological effects of Hickory tree and bark. J Trop Med 2008; 8: 3.
[5]
Wan L, Chen X. Study on anti-inflammatory and analgesic effects of walnut peel. Pharmacology and Clinic of Chinese Medicine 1999; 15: 2.
[6]
Liu ZB, Zhang T, Ye X, et al. Natural substances derived from herbs or plants are promising sources of anticancer agents against colorectal cancer via triggering apoptosis. J Pharm Pharmacol 2022; 74(2): 162-78.
[http://dx.doi.org/10.1093/jpp/rgab130] [PMID: 34559879]
[7]
Vermeulen K, Van Bockstaele DR, Berneman ZN. Apoptosis: mechanisms and relevance in cancer. Ann Hematol 2005; 84(10): 627-39.
[http://dx.doi.org/10.1007/s00277-005-1065-x] [PMID: 16041532]
[8]
Liu X, Chen Y, Zhang Y, et al. Juglone potentiates TRAIL-induced apoptosis in human melanoma cells via activating the ROS-p38-p53 pathway. Mol Med Rep 2017; 16(6): 9645-51.
[http://dx.doi.org/10.3892/mmr.2017.7806] [PMID: 29039537]
[9]
Dilek Bayram. Determination of apoptotic effect of juglone on human bladder cancer TCC-SUP and RT-4 cells: An in vitro study. J Environ Pathol Toxicol Oncol 2018; 37(2): 173-81.
[10]
Huang R, Dai Q, Yang R, et al. A review: PI3K/AKT/mTOR signaling pathway and its regulated eukaryotic translation initiation factors may be a potential therapeutic target in esophageal squamous cell carcinoma. Front Oncol 2022; 12: 817916.
[http://dx.doi.org/10.3389/fonc.2022.817916] [PMID: 35574327]
[11]
Peng Y, Wang Y, Zhou C, Mei W, Zeng C. PI3K/Akt/mTOR pathway and its role in cancer therapeutics: Are we making headway? Front Oncol 2022; 12: 819128.
[http://dx.doi.org/10.3389/fonc.2022.819128] [PMID: 35402264]
[12]
Mafi S, Mansoori B, Taeb S, et al. mTOR-mediated regulation of immune responses in cancer and tumor microenvironment. Front Immunol 2022; 12: 774103.
[http://dx.doi.org/10.3389/fimmu.2021.774103] [PMID: 35250965]
[13]
Karki R, Man SM, Malireddi RKS, et al. NLRC3 is an inhibitory sensor of PI3K-mTOR pathways in cancer. Nature 2016; 540(7634): 583-7.
[http://dx.doi.org/10.1038/nature20597] [PMID: 27951586]
[14]
Yang H, Ma Y, Gao C, et al. Five novel diarylheptanoids from green walnut husks (Juglans regia L.). Fitoterapia 2019; 134: 221-5.
[http://dx.doi.org/10.1016/j.fitote.2019.03.002] [PMID: 30840915]
[15]
Yang H, Gan C, Guo Y, et al. Juglans mandshurica two novel compounds from green walnut husks (Maxim.). Nat Prod Res 2022; 36: 3389-95.
[PMID: 33342293]
[16]
Alzahrani AS. PI3K/Akt/mTOR inhibitors in cancer: At the bench and bedside. Semin Cancer Biol 2019; 59: 125-32.
[http://dx.doi.org/10.1016/j.semcancer.2019.07.009] [PMID: 31323288]
[17]
Drullinsky PR, Hurvitz SA. Mechanistic basis for PI3K inhibitor antitumor activity and adverse reactions in advanced breast cancer. Breast Cancer Res Treat 2020; 181(2): 233-48.
[http://dx.doi.org/10.1007/s10549-020-05618-1] [PMID: 32274666]
[18]
Janku F, Yap TA, Meric-Bernstam F. Targeting the PI3K pathway in cancer: are we making headway? Nat Rev Clin Oncol 2018; 15(5): 273-91.
[http://dx.doi.org/10.1038/nrclinonc.2018.28] [PMID: 29508857]
[19]
Harton JA, Linhoff MW, Zhang J, Ting JPY. Cutting edge: CATERPILLER: A large family of mammalian genes containing CARD, pyrin, nucleotide-binding, and leucine-rich repeat domains. J Immunol 2002; 169(8): 4088-93.
[http://dx.doi.org/10.4049/jimmunol.169.8.4088] [PMID: 12370334]
[20]
Conti BJ, Davis BK, Zhang J, O’Connor W Jr, Williams KL, Ting JPY. CATERPILLER 16.2 (CLR16.2), a novel NBD/LRR family member that negatively regulates T cell function. J Biol Chem 2005; 280(18): 18375-85.
[http://dx.doi.org/10.1074/jbc.M413169200] [PMID: 15705585]
[21]
Liu R, Truax AD, Chen L, et al. Expression profile of innate immune receptors, NLRs and AIM2, in human colorectal cancer: Correlation with cancer stages and inflammasome components. Oncotarget 2015; 6(32): 33456-69.
[http://dx.doi.org/10.18632/oncotarget.5587] [PMID: 26378020]
[22]
Shiwarski DJ, Darr M, Telmer CA, Bruchez MP, Puthenveedu MA. PI3K class II α regulates δ-opioid receptor export from the trans -Golgi network. Mol Biol Cell 2017; 28(16): 2202-19.
[http://dx.doi.org/10.1091/mbc.e17-01-0030] [PMID: 28566554]
[23]
Riehle RD, Cornea S, Degterev A. Role of phosphatidylinositol 3,4,5-trisphosphate in cell signaling. Adv Exp Med Biol 2013; 991: 105-39.
[http://dx.doi.org/10.1007/978-94-007-6331-9_7] [PMID: 23775693]
[24]
Mayer IA, Arteaga CL. The PI3K/AKT pathway as a target for cancer treatment. Annu Rev Med 2016; 67(1): 11-28.
[http://dx.doi.org/10.1146/annurev-med-062913-051343] [PMID: 26473415]
[25]
Wang R, Song F, Li S, Wu B, Gu Y, Yuan Y. Salvianolic acid A attenuates CCl4-induced liver fibrosis by regulating the PI3K/AKT/mTOR, Bcl-2/Bax and caspase-3/cleaved caspase-3 signaling pathways. Drug Des Devel Ther 2019; 13: 1889-900.
[http://dx.doi.org/10.2147/DDDT.S194787] [PMID: 31213776]
[26]
Li R, Ding C, Zhang J, et al. Modulation of Bax and mTOR for cancer therapeutics. Cancer Res 2017; 77(11): 3001-12.
[http://dx.doi.org/10.1158/0008-5472.CAN-16-2356] [PMID: 28381544]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy