Matrine Alkaloids Modulating DNA Damage Repair in Chemoresistant Non-small Cell Lung Cancer Cells

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2024 Oct 16

PMID 39415176

Authors

Fengping Wang

Jun Liu

Wenliang Liao

Lixiang Zheng

Shuai Qian

Lisi Mao

Affiliations

Soon will be listed here.

Abstract

Background: Non-small cell lung cancer (NSCLC) presents a significant challenge in the medical field due to its high incidence and resistance to chemotherapy. Chemoresistance in NSCLC diminishes treatment efficacy and contributes to poor patient outcomes. Matrine alkaloids have shown promise in reversing chemotherapy resistance in NSCLC by targeting DNA repair mechanisms.

Methods: Utilizing molecular dynamics simulations, we explored the interactions between Matrine alkaloids and DNA repair-related proteins to elucidate their impact on NSCLC cells. In vitro experiments involved treating A549/DDP cells with Matrine alkaloids to evaluate their sensitizing effects on lung cancer cells. Additionally, animal model experiments were conducted to validate the therapeutic potential of Matrine alkaloids in NSCLC treatment.

Results: Our findings demonstrate that Matrine alkaloids disrupt DNA damage repair processes in NSCLC cells, leading to increased sensitivity to chemotherapy. Molecular docking studies revealed the intricate mechanisms by which Matrine alkaloids interact with DNA repair proteins, impacting cell survival and proliferation. Both cell experiments and animal models confirmed the chemosensitizing effects of Matrine alkaloids in NSCLC treatment.

Conclusion: Matrine alkaloids offer a promising avenue for overcoming chemotherapy resistance in NSCLC by interfering with DNA repair pathways. This study lays a solid foundation for future clinical investigations into the potential of Matrine alkaloids as effective therapeutic agents for enhancing NSCLC treatment outcomes.

References

Wang M, Herbst R, Boshoff C . Toward personalized treatment approaches for non-small-cell lung cancer. Nat Med. 2021; 27(8):1345-1356. DOI: 10.1038/s41591-021-01450-2. View

Zeng Y, Zhang Z, Chen H, Fan J, Yuan W, Li J . Comprehensive Analysis of Immune Implication and Prognostic Value of in Non-Small Cell Lung Cancer. Front Oncol. 2022; 11:798425. PMC: 8761744. DOI: 10.3389/fonc.2021.798425. View

Chen M, Gu Y, Zhang A, Sze D, Mo S, May B . Biological effects and mechanisms of matrine and other constituents of Sophora flavescens in colorectal cancer. Pharmacol Res. 2021; 171:105778. DOI: 10.1016/j.phrs.2021.105778. View

Zhu L, Huang S, Li J, Chen J, Yao Y, Li L . Sophoridine inhibits lung cancer cell growth and enhances cisplatin sensitivity through activation of the p53 and Hippo signaling pathways. Gene. 2020; 742:144556. DOI: 10.1016/j.gene.2020.144556. View

Trick A, Chen F, Schares J, Freml B, Lor P, Yun Y . High resolution estimates of relative gene abundance with quantitative ratiometric regression PCR (qRR-PCR). Analyst. 2021; 146(21):6463-6469. PMC: 8627783. DOI: 10.1039/d1an01397a. View

Pilipovic A, Mitrovic D, Obradovic S, Posa M . Docking-based analysis and modeling of the activity of bile acids and their synthetic analogues on large conductance Ca2+ activated K channels in smooth muscle cells. Eur Rev Med Pharmacol Sci. 2021; 25(23):7501-7507. DOI: 10.26355/eurrev_202112_27449. View

Zhang X, Xu H, Bi X, Hou G, Liu A, Zhao Y . Src acts as the target of matrine to inhibit the proliferation of cancer cells by regulating phosphorylation signaling pathways. Cell Death Dis. 2021; 12(10):931. PMC: 8511016. DOI: 10.1038/s41419-021-04221-6. View

Kinner A, Wu W, Staudt C, Iliakis G . Gamma-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin. Nucleic Acids Res. 2008; 36(17):5678-94. PMC: 2553572. DOI: 10.1093/nar/gkn550. View

Jia X, Xin M, Xu J, Xiang X, Li X, Jiao Y . Inhibition of autophagy potentiates the cytotoxicity of the irreversible FGFR1-4 inhibitor FIIN-2 on lung adenocarcinoma. Cell Death Dis. 2022; 13(8):750. PMC: 9428205. DOI: 10.1038/s41419-022-05201-0. View

10.

Zhou K, Huang S, Hu L, Zhang X, Qin W, Zhang Y . Increased Nuclear Transporter KPNA2 Contributes to Tumor Immune Evasion by Enhancing PD-L1 Expression in PDAC. J Immunol Res. 2021; 2021:6694392. PMC: 7939744. DOI: 10.1155/2021/6694392. View

11.

Altorki N, Wang X, Kozono D, Watt C, Landrenau R, Wigle D . Lobar or Sublobar Resection for Peripheral Stage IA Non-Small-Cell Lung Cancer. N Engl J Med. 2023; 388(6):489-498. PMC: 10036605. DOI: 10.1056/NEJMoa2212083. View

12.

Safran M, Dalah I, Alexander J, Rosen N, Iny Stein T, Shmoish M . GeneCards Version 3: the human gene integrator. Database (Oxford). 2010; 2010:baq020. PMC: 2938269. DOI: 10.1093/database/baq020. View

13.

Luo D, Dai X, Tian H, Fan C, Xie H, Chen N . Sophflarine A, a novel matrine-derived alkaloid from Sophora flavescens with therapeutic potential for non-small cell lung cancer through ROS-mediated pyroptosis and autophagy. Phytomedicine. 2023; 116:154909. DOI: 10.1016/j.phymed.2023.154909. View

14.

Sun K, Zhang Y, Li Y, Yang P, Sun Y . Biochemical Targets and Molecular Mechanism of Matrine against Aging. Int J Mol Sci. 2023; 24(12). PMC: 10299030. DOI: 10.3390/ijms241210098. View

15.

Gong X, Gao Y, Guo G, Vondran F, Schwartlander R, Efimova E . Effect of matrine on primary human hepatocytes in vitro. Cytotechnology. 2014; 67(2):255-65. PMC: 4329302. DOI: 10.1007/s10616-013-9680-1. View

16.

Li X, Tang Z, Wen L, Jiang C, Feng Q . Matrine: A review of its pharmacology, pharmacokinetics, toxicity, clinical application and preparation researches. J Ethnopharmacol. 2020; 269:113682. DOI: 10.1016/j.jep.2020.113682. View

17.

Li W, Zhang S, Liu J, Liu Y, Liang Q . Vitamin K2 stimulates MC3T3‑E1 osteoblast differentiation and mineralization through autophagy induction. Mol Med Rep. 2019; 19(5):3676-3684. PMC: 6472126. DOI: 10.3892/mmr.2019.10040. View

18.

Zhang T, Li B . [Application Progress of Immune Checkpoint Inhibitors  in Oncogene-driven Advanced Non-small Cell Lung Cancer]. Zhongguo Fei Ai Za Zhi. 2021; 24(3):188-195. PMC: 8143967. DOI: 10.3779/j.issn.1009-3419.2021.101.04. View

19.

Yu G, Wang L, Han Y, He Q . clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012; 16(5):284-7. PMC: 3339379. DOI: 10.1089/omi.2011.0118. View

20.

Xu Y, Wang X, Sa K, Li H, Chen L . Alkaloids from the roots of Sophora flavescens and their anti-tumor activity. Fitoterapia. 2023; 171:105685. DOI: 10.1016/j.fitote.2023.105685. View