Skip to content
2000
image of Mechanistic Overview on the Therapeutic Potential of Alkaloids in Combating Non-small Cell Lung Carcinoma

Abstract

Non-Small Cell Lung Cancer (NSCLC) holds a significant position globally among cancer types. Alkaloids, which are natural compounds containing nitrogen atoms, are found in various plant sources and play a crucial role in anti-cancer activity, offering potential therapeutic applications. They are classified by their chemical structure into categories such as indole alkaloids, isoquinoline alkaloids, pyrrole and pyrrolizidine alkaloids, β-carboline and benzoquinolizidine alkaloids, quinazoline alkaloids, and diterpene alkaloids. Alkaloid-based treatments offer several advantages in drug design, including high bioavailability, lower toxicity, and effective therapeutic outcomes. Drugs like vinca alkaloids, camptothecin, and sanguinarine demonstrate high efficacy against lung cancer cells. Combination therapy involving alkaloids can prevent chemoresistance and exhibit high potency against cancer cells. This review highlights the importance of alkaloids in combating chemoresistance in lung cancer. The mechanisms by which alkaloids inhibit the EGFR/AKT/MAPK signaling pathways and induce apoptosis are discussed in detail. In the future, alkaloid-based therapeutics for NSCLC and other malignancies may be explored as advanced and effective treatment options.

Loading

Article metrics loading...

/content/journals/npj/10.2174/0122103155322306241021043330
2024-10-30
2025-01-27
Loading full text...

Full text loading...

References

  1. Chaitanya Thandra K. Barsouk A. Saginala K. Sukumar Aluru J. Barsouk A. Epidemiology of lung cancer. Contemp. Oncol. (Pozn.) 2021 25 1 45 52 10.5114/wo.2021.103829 33911981
    [Google Scholar]
  2. Araghi M. Mannani R. Heidarnejad maleki A. Hamidi A. Rostami S. Safa S.H. Faramarzi F. Khorasani S. Alimohammadi M. Tahmasebi S. Akhavan-Sigari R. Recent advances in non-small cell lung cancer targeted therapy; an update review. Cancer Cell Int. 2023 23 1 162 10.1186/s12935‑023‑02990‑y 37568193
    [Google Scholar]
  3. Sathishkumar K. Chaturvedi M. Das P. Stephen S. Mathur P. Cancer incidence estimates for 2022 & projection for 2025: Result from national cancer registry programme, India. Indian J. Med. Res. 2022 156 4&5 598 607 36510887
    [Google Scholar]
  4. Herbst R.S. Non-small cell lung cancer. 2023 Available from: https://www.yalemedicine.org/
  5. Mathur P. Nath A. Sathishkumar K. Das P. Sudarshan K.L. A clinicoepidemiological profile of lung cancers in India – Results from the national cancer registry programme. Indian J. Med. Res. 2022 155 2 264 272 10.4103/ijmr.ijmr_1364_21 35946203
    [Google Scholar]
  6. Raso M. G. Wistuba I. I. Molecular pathogenesis of early-stage non-small cell lung cancer and a proposal for tissue banking to facilitate identification of new biomarkers. J Thorac Oncol. 2007 2 7 Suppl 3 S128 S135
    [Google Scholar]
  7. Villalobos P. Wistuba I.I. Lung I. Cancer biomarkers. Hematol. Oncol. Clin. North Am. 2017 31 1 13 29 10.1016/j.hoc.2016.08.006 27912828
    [Google Scholar]
  8. The ABCs and 123s of Cancer Stages. Lane regional medical centre Accessed December 18, 2023
  9. Webb S.D. Sherratt J.A. Fish R.G. Mathematical modelling of tumour acidity: Regulation of intracellular pH. J. Theor. Biol. 1999 196 2 237 250 10.1006/jtbi.1998.0836 9990741
    [Google Scholar]
  10. Chen S. Tang J. Liu F. Li W. Yan T. Shangguan D. Yang N. Liao D. Changes of tumor microenvironment in non-small cell lung cancer after TKI treatments. Front. Immunol. 2023 14 1094764 10.3389/fimmu.2023.1094764 36949948
    [Google Scholar]
  11. Saini N. Grewal A.S. Lather V. Gahlawat S.K. Natural alkaloids targeting EGFR in non-small cell lung cancer: Molecular docking and ADMET predictions. Chem. Biol. Interact. 2022 358 109901 10.1016/j.cbi.2022.109901 35341731
    [Google Scholar]
  12. Huang S. He T. Yang S. Sheng H. Tang X. Bao F. Wang Y. Lin X. Yu W. Cheng F. Lv W. Hu J. Metformin reverses chemoresistance in non-small cell lung cancer via accelerating ubiquitination-mediated degradation of Nrf2. Transl. Lung Cancer Res. 2020 9 6 2337 2355 10.21037/tlcr‑20‑1072 33489797
    [Google Scholar]
  13. Naidu S. Garofalo M. microRNAs: An emerging paradigm in lung cancer chemoresistance. Front. Med. (Lausanne) 2015 2 77 10.3389/fmed.2015.00077 26583081
    [Google Scholar]
  14. Dey P. Kundu A. Kumar A. Gupta M. Lee B.M. Analysis of alkaloids (indole alkaloids, isoquinoline alkaloids, tropane alkaloids). Recent Advances in Natural Products Analysis. 2020 505 567
    [Google Scholar]
  15. Heinrich M. Mah J. Amirkia V. Alkaloids used as medicines: Structural phytochemistry meets biodiversity—an update and forward look. Molecules 2021 26 7 1836 10.3390/molecules26071836 33805869
    [Google Scholar]
  16. Alkaloid | definition, structure, & classification 2017 Available from: https://www.britannica.com/science/alkaloid
  17. History of antimalarial drugs | medicines for malaria venture 2017 Available from: https://www.mmv.org/malaria-medicines/history-antimalarials-drugs
  18. Taur D.J. Patil R.Y. Some medicinal plants with antiasthmatic potential: A current status. Asian Pac. J. Trop. Biomed. 2011 1 5 413 418 10.1016/S2221‑1691(11)60091‑9 23569804
    [Google Scholar]
  19. Iqbal J. Abbasi B.A. Mahmood T. Kanwal S. Ali B. Shah S.A. Khalil A.T. Plant-derived anticancer agents: A green anticancer approach. Asian Pac. J. Trop. Biomed. 2017 7 12 1129 1150 10.1016/j.apjtb.2017.10.016
    [Google Scholar]
  20. Vardanyan R Hruby V Cholinomimetics. Synthesis of best-seller drugs. 2016 Available from: https://www.sciencedirect.com/book/9780124114920/synthesis-of-best-seller-drugs
  21. Luna-Vázquez F. Ibarra-Alvarado C. Rojas-Molina A. Rojas-Molina I. Zavala-Sánchez M. Vasodilator compounds derived from plants and their mechanisms of action. Molecules 2013 18 5 5814 5857 10.3390/molecules18055814 23685938
    [Google Scholar]
  22. Tamargo J. Delpón E. Pharmacological Bases of Antiarrhythmic Therapy. Cardiac Electrophysiology: From Cell to Bedside: Seventh Edition 2018 513 524
    [Google Scholar]
  23. Jiang W. Tang M. Yang L. Zhao X. Gao J. Jiao Y. Li T. Tie C. Gao T. Han Y. Jiang J.D. Analgesic alkaloids derived from traditional chinese medicine in pain management. Front. Pharmacol. 2022 13 851508 10.3389/fphar.2022.851508 35620295
    [Google Scholar]
  24. Mabhiza D. Chitemerere T. Mukanganyama S. Antibacterial properties of alkaloid extracts from Callistemon citrinus and vernonia adoensis against staphylococcus aureus and pseudomonas aeruginosa. Int. J. Med. Chem. 2016 2016 1 7 10.1155/2016/6304163 26904285
    [Google Scholar]
  25. Behl T. Gupta A. Albratty M. Najmi A. Meraya A.M. Alhazmi H.A. Anwer M.K. Bhatia S. Bungau S.G. Alkaloidal phytoconstituents for diabetes management: Exploring the unrevealed potential. Molecules 2022 27 18 5851 10.3390/molecules27185851 36144587
    [Google Scholar]
  26. Kalix P. The pharmacology of psychoactive alkaloids from ephedra and catha. J. Ethnopharmacol. 1991 32 1-3 201 208 10.1016/0378‑8741(91)90119‑X 1881158
    [Google Scholar]
  27. Kaur K. Alkaloids-important therapeutic secondary metabolites of plant origin. J Crit Rev 2015 2 3 1 8
    [Google Scholar]
  28. Lichman B.R. The scaffold-forming steps of plant alkaloid biosynthesis. Nat. Prod. Rep. 2021 38 1 103 129 10.1039/D0NP00031K 32745157
    [Google Scholar]
  29. Castejón-Vega B. Rubio A. Pérez-Pulido A.J. Quiles J.L. Lane J.D. Fernández-Domínguez B. Cachón-González M.B. Martín-Ruiz C. Sanz A. Cox T.M. Alcocer-Gómez E. Cordero M.D. L-arginine ameliorates defective autophagy in GM2 gangliosidoses by mTOR modulation. Cells 2021 10 11 3122 10.3390/cells10113122 34831346
    [Google Scholar]
  30. Adibah K. Plant toxins: Alkaloids and their toxicities. GSC Biological and Pharmaceutical Sciences 2019 6 2
    [Google Scholar]
  31. Rowinsky Eric The Vinca Alkaloids, microtubule-targetting natural products. Holland-Frei Cancer Medicine, 6th edition NCBI Bookshelf 2023
    [Google Scholar]
  32. Li F. Jiang T. Li Q. Ling X. Camptothecin (CPT) and its derivatives are known to target topoisomerase I (Top1) as their mechanism of action: Did we miss something in CPT analogue molecular targets for treating human disease such as cancer? Am. J. Cancer Res. 2017 7 12 2350 2394 29312794
    [Google Scholar]
  33. Mollica A. Locatelli M. Stefanucci A. Pinnen F. Synthesis and bioactivity of secondary metabolites from marine sponges containing dibrominated indolic systems. Molecules 2012 17 5 6083 6099 10.3390/molecules17056083 22614862
    [Google Scholar]
  34. Reyes F. Fernández R. Rodríguez A. Francesch A. Taboada S. Ávila C. Cuevas C. Aplicyanins A–F, new cytotoxic bromoindole derivatives from the marine tunicate Aplidium cyaneum. Tetrahedron 2008 64 22 5119 5123 10.1016/j.tet.2008.03.060
    [Google Scholar]
  35. Prabhu K. S. Bhat A, A. Siveen K. S. Kuttikrishnan S. Raza S. S. Raheed T. Jochebeth A. Khan A. Q. Chawdhery M. Z. Haris M. Kulinski M. Dermime S. Steinhoff M. Uddin S. Sanguinarine mediated apoptosis in non-small cell lung cancer via generation of reactive oxygen species and suppression of JAK/STAT pathway. Biomed Pharmacother. 2021 144 112358
    [Google Scholar]
  36. Li L. Xu Y. Wang B. Liriodenine induces the apoptosis of human laryngocarcinoma cells via the upregulation of p53 expression. Oncol. Lett. 2015 9 3 1121 1127 10.3892/ol.2014.2834 25663867
    [Google Scholar]
  37. Luan F. He X. Zeng N. Tetrandrine: A review of its anticancer potentials, clinical settings, pharmacokinetics and drug delivery systems. J. Pharm. Pharmacol. 2020 72 11 1491 1512 10.1111/jphp.13339 32696989
    [Google Scholar]
  38. Achi I.T. Sarbadhikary P. George B.P. Abrahamse H. Multi-target potential of berberine as an antineoplastic and antimetastatic agent: A special focus on lung cancer treatment. Cells 2022 11 21 3433 10.3390/cells11213433 36359829
    [Google Scholar]
  39. Liu W. Qi Y. Liu L. Tang Y. Wei J. Zhou L. Suppression of tumor cell proliferation by quinine via the inhibition of the tumor necrosis factor receptor-associated factor 6-AKT interaction. Mol. Med. Rep. 2016 14 3 2171 2179 10.3892/mmr.2016.5492 27430155
    [Google Scholar]
  40. Krishnamoorthi S. Kasinathan G.N. Paramasivam G. Rath S.N. Prakash J. Selective targeting of lung cancer cells with methylparaben-tethered-quinidine cocrystals in 3D spheroid models. ACS Omega 2023 8 49 46628 46639 10.1021/acsomega.3c05617 38107962
    [Google Scholar]
  41. Wang H. Shi Y. Ma D. Cao M. Sun Y. Jiang X. Xu Z. Wang Y. Yang Y. Shi Y. Wang K. Cinchonine exerts anti-tumor and immunotherapy sensitizing effects in lung cancer by impairing autophagic-lysosomal degradation. Biomed Pharmacother. 2023 164 114980
    [Google Scholar]
  42. Rodilla A.M. Korrodi-Gregório L. Hernando E. Manuel-Manresa P. Quesada R. Pérez-Tomás R. Soto-Cerrato V. Synthetic tambjamine analogues induce mitochondrial swelling and lysosomal dysfunction leading to autophagy blockade and necrotic cell death in lung cancer. Biochem. Pharmacol. 2017 126 23 33 10.1016/j.bcp.2016.11.022 27890727
    [Google Scholar]
  43. Yu Q. Luo J. Zhang J. Chen Y. Chen K. Lin J. Sun S. Lin X. Oxymatrine inhibits the development of non-small cell lung cancer through miR-367-3p upregulation and target gene SGK3 downregulation. Am. J. Transl. Res. 2020 12 9 5538 5550 33042436
    [Google Scholar]
  44. Ahmad I. Khan H. Usman Amin M. Khalid S. Behl T. Ur Rahman N. An overview on the anticancer potential of punarnavine: prediction of drug-like properties. Oncologie 2021 23 3 321 333 10.32604/Oncologie.2021.018296
    [Google Scholar]
  45. Zhu G. Yin F. Deng X. [Effect of NF-kappaB on inhibition of non-small cell lung cancer cell cyclooxygenase-2 by brucine]. Zhongguo Zhongyao Zazhi 2012 37 9 1269 1273 22803374
    [Google Scholar]
  46. Do M.T. Kim H.G. Choi J.H. Khanal T. Park B.H. Tran T.P. Jeong T.C. Jeong H.G. Antitumor efficacy of piperine in the treatment of human HER2-overexpressing breast cancer cells. Food Chem. 2013 141 3 2591 2599 10.1016/j.foodchem.2013.04.125 23870999
    [Google Scholar]
  47. Yeo W. L. Riely G. J. Yeap B. Y. Lau M. W. Warner J. L. Bodio K. Huberman M. S. Kris M. G. Tenen D. G. Pao W. Kobayashi S. Costa D. B. Erlotinib at a dose of 25 mg daily for non-small cell lung cancers with EGFR mutations. J Thorac Oncol. 2010 5 7 1048 1053
    [Google Scholar]
  48. Du G. H. GH. Paclitaxel. 18 Available from: https://go.drugbank.com/drugs/DB01229
  49. Moudi M. Go R. Yien C.Y. Nazre M. Vinca alkaloids. Int. J. Prev. Med. 2013 4 11 1231 1235 24404355
    [Google Scholar]
  50. S M A spotlight on alkaloid nanoformulations for the treatment of lung cancer. Front. Oncol. 2022 12 994155
    [Google Scholar]
  51. Zhang Y.W. Kong X.Y. Wang J.H. Du G.H. Vinblastine and Vincristine. Natural Small Molecule Drugs from Plants 2018 551 562
    [Google Scholar]
  52. Cisplatin + Vinblastine + Radiation 2023 Available from: https://www.chemoexperts.com/cisplatin-vinblastine-radiation-nsclc.html#:~:text=Cisplatin%20and%20vinblastine%20are%20chemotherapy,the%20effects%20of%20the%20radiation. 2017
  53. Radiation therapy plus chemotherapy in treating patients with non-small cell lung cancer Patent NCT01134861, 2017
  54. Surgery with or without preoperative chemotherapy in treating patients with resectable non-small cell lung cancer Patent NCT00003159, 2017
  55. Rosell R Combination chemotherapy compared with no treatment following surgery in treating patients with non-small cell lung cancer 2023 Available from: https://clinicaltrials.gov/
  56. Jaferian S. Soleymaninejad M. Daraee H. Verapamil (VER) enhances the cytotoxic effects of docetaxel and vinblastine combined therapy against non-small cell lung cancer cell lines. Drug Res. (Stuttg.) 2018 68 3 146 152 10.1055/s‑0043‑117895 29132176
    [Google Scholar]
  57. Zhou C. Zhu Y. Lu B. Zhao W. Zhao X. Survivin expression modulates the sensitivity of A549 lung cancer cells resistance to vincristine. Oncol. Lett. 2018 16 4 5466 5472 10.3892/ol.2018.9277 30250619
    [Google Scholar]
  58. Samadi N. Ghanbari P. Mohseni M. Tabasinezhad M. Sharifi S. Nazemieh H. Rashidi M. Combination therapy increases the efficacy of docetaxel, vinblastine and tamoxifen in cancer cells. J. Cancer Res. Ther. 2014 10 3 715 721 10.4103/0973‑1482.139152 25313766
    [Google Scholar]
  59. Kang D.H. Park D.I. Chung C. Moon J.Y. Park H.S. Jung S.S. Kim J.O. Lee J.E. Efficacy of weekly vinorelbine monotherapy in patients with lung adenocarcinoma. J. Clin. Oncol. 2018 36 15_suppl e21157 10.1200/JCO.2018.36.15_suppl.e21157
    [Google Scholar]
  60. Li H. Sun L. Li H. Lv X. Semukunzi H. Li R. Yu J. Yuan S. Lin S. DT-13 synergistically enhanced vinorelbine-mediated mitotic arrest through inhibition of FOXM1-BICD2 axis in non-small-cell lung cancer cells. Cell Death Dis. 2017 8 5 e2810 10.1038/cddis.2017.218 28542137
    [Google Scholar]
  61. Kaburaki K. Isobe K. Kobayashi H. Yoshizawa T. Takai Y. Homma S. A feasibility study of bevacizumab and vinorelbine in patients with previously treated advanced non-squamous non-small-cell lung cancer. Mol. Clin. Oncol. 2017 6 4 510 514 10.3892/mco.2017.1187 28413657
    [Google Scholar]
  62. Genova C. Alama A. Coco S. Rijavec E. Dal Bello M.G. Vanni I. Biello F. Barletta G. Rossi G. Grossi F. Vinflunine for the treatment of non-small cell lung cancer. Expert Opin. Investig. Drugs 2016 25 12 1447 1455 10.1080/13543784.2016.1252331 27771969
    [Google Scholar]
  63. Yamazaki Y. Urano A. Sudo H. Kitajima M. Takayama H. Yamazaki M. Aimi N. Saito K. Metabolite profiling of alkaloids and strictosidine synthase activity in camptothecin producing plants. Phytochemistry 2003 62 3 461 470 10.1016/S0031‑9422(02)00543‑5 12620359
    [Google Scholar]
  64. Chiu Y.H. Hsu S.H. Hsu H.W. Huang K.C. Liu W. Wu C.Y. Huang W.P. Chen J. Chen B.H. Chiu C.C. Human non‑small cell lung cancer cells can be sensitized to camptothecin by modulating autophagy. Int. J. Oncol. 2018 53 5 1967 1979 10.3892/ijo.2018.4523 30106130
    [Google Scholar]
  65. Raj A. Thomas R.K. Vidya L. Aparna V.M. Neelima S. Sudarsanakumar C. Exploring the cytotoxicity on human lung cancer cells and DNA binding stratagem of camptothecin functionalised silver nanoparticles through multi-spectroscopic, and calorimetric approach. Sci. Rep. 2023 13 1 9045 10.1038/s41598‑023‑34997‑w 37270606
    [Google Scholar]
  66. Xie J. Wang H. Huang Q. Lin J. Wen H. Miao Y. Lv L. Ruan D. Yu X. Qin L. Zhou Y. Enhanced cytotoxicity to lung cancer cells by mitochondrial delivery of camptothecin. Eur J Pharm Sci. 2023 189 106561
    [Google Scholar]
  67. Dai X. Wu G. Zhang Y. Zhang X. Yin R. Qi X. Li J. Jiang T. Design, synthesis, and in vitro/in vivo anti-cancer activities of novel (20S)-10,11-methylenedioxy-camptothecin heterocyclic derivatives. Int. J. Mol. Sci. 2020 21 22 8495 10.3390/ijms21228495 33187360
    [Google Scholar]
  68. Panda M. Biswal S. Biswal B.K. Evodiamine potentiates cisplatin-induced cell death and overcomes cisplatin resistance in non-small-cell lung cancer by targeting SOX9-β‐catenin axis. Mol. Biol. Rep. 2024 51 1 523 10.1007/s11033‑024‑09477‑7 38630183
    [Google Scholar]
  69. Feng G. He J. Li Q. Bai M. Liu K. Liu X. Yi X. Liu Y. Luo L. Gao C. New alkaloids and steroids from hydranth of goniopora columna corals and their inhibiting lung cancer cell activities. Chem. Biodivers. 2024 21 4 e202301993 10.1002/cbdv.202301993 38342755
    [Google Scholar]
  70. Islam Z. Islam S.M.R. Hossen F. Mahtab-ul-Islam K. Hasan M.R. Karim R. Moringa oleifera is a prominent source of nutrients with potential health benefits. Int. J. Food Sci. 2021 2021 1 11 10.1155/2021/6627265 34423026
    [Google Scholar]
  71. Bhadresha K. Thakore V. Brahmbhatt J. Upadhyay V. Jain N. Rawal R. Anticancer effect of moringa oleifera leaves extract against lung cancer cell line via induction of apoptosis. Advances in Cancer Biology - Metastasis 2022 6 100072 10.1016/j.adcanc.2022.100072
    [Google Scholar]
  72. Makarević J. Rutz J. Juengel E. Kaulfuss S. Reiter M. Tsaur I. Bartsch G. Haferkamp A. Blaheta R.A. Amygdalin blocks bladder cancer cell growth in vitro by diminishing cyclin A and cdk2. PLoS One 2014 9 8 e105590 10.1371/journal.pone.0105590 25136960
    [Google Scholar]
  73. Qian L. Xie B. Wang Y. Qian J. Amygdalin-mediated inhibition of non-small cell lung cancer cell invasion in vitro. Int. J. Clin. Exp. Pathol. 2015 8 5 5363 5370 26191238
    [Google Scholar]
  74. Bisset N.G. Plants as a source of isoquinoline alkaloids. The Chemistry and Biology of Isoquinoline Alkaloids. Proceedings in Life Sciences Berlin, Heidelberg,1985, pp.1-22 10.1007/978‑3‑642‑70128‑3_1
    [Google Scholar]
  75. Basu P. Kumar G.S. Sanguinarine and its role in chronic diseases. Adv. Exp. Med. Biol. 2016 928 155 172 10.1007/978‑3‑319‑41334‑1_7 27671816
    [Google Scholar]
  76. Yang J. Wang X. Gao Y. Fang C. Ye F. Huang B. Li L. Inhibition of PI3K-AKT signaling blocks PGE2-induced COX-2 expression in lung adenocarcinoma. OncoTargets Ther. 2020 13 8197 8208 10.2147/OTT.S263977 32904445
    [Google Scholar]
  77. Xu R. Wu J. Luo Y. Wang Y. Tian J. Teng W. Zhang B. Fang Z. Li Y. Sanguinarine represses the growth and metastasis of non-small cell lung cancer by facilitating ferroptosis. Curr. Pharm. Des. 2022 28 9 760 768 10.2174/1381612828666220217124542 35176976
    [Google Scholar]
  78. Li B. Luo Y. Zhou Y. Wu J. Fang Z. Li Y. Role of sanguinarine in regulating immunosuppression in a lewis lung cancer mouse model. Int. Immunopharmacol. 2022 110 108964 10.1016/j.intimp.2022.108964 35728305
    [Google Scholar]
  79. Gu S. Yang X.C. Xiang X.Y. Wu Y. Zhang Y. Yan X.Y. Xue Y.N. Sun L.K. Shao G.G. Sanguinarine-induced apoptosis in lung adenocarcinoma cells is dependent on reactive oxygen species production and endoplasmic reticulum stress. Oncol. Rep. 2015 34 2 913 919 10.3892/or.2015.4054 26081590
    [Google Scholar]
  80. Chang H.C. Chang F.R. Wu Y.C. Lai Y.H. Anti-cancer effect of liriodenine on human lung cancer cells. Kaohsiung J. Med. Sci. 2004 20 8 365 371 10.1016/S1607‑551X(09)70172‑X 15473647
    [Google Scholar]
  81. Lan J. Wang N. Huang L. Liu Y. Ma X. Lou H. Chen C. Feng Y. Pan W. Design and synthesis of novel tetrandrine derivatives as potential anti-tumor agents against human hepatocellular carcinoma. Eur. J. Med. Chem. 2017 127 554 566 10.1016/j.ejmech.2017.01.008 28109948
    [Google Scholar]
  82. Guo J. Gu X. Mai Y. Zhao Y. Gou G. Yang J. Preparation and characterisation of tetrandrine nanosuspensions and in vitro estimate antitumour activity on A549 lung cancer cell line. J. Microencapsul. 2020 37 5 384 393 10.1080/02652048.2020.1761905 32349635
    [Google Scholar]
  83. Chen Z. Zhao L. Zhao F. Yang G. Wang J. Tetrandrine suppresses lung cancer growth and induces apoptosis, potentially via the VEGF/HIF-1α/ICAM-1 signaling pathway. Oncol. Lett. 2018 15 5 7433 7437 10.3892/ol.2018.8190 29849794
    [Google Scholar]
  84. Wang C. Yang J. Guo Y. Shen J. Pei X. Anticancer activity of tetrandrine by inducing apoptosis in human breast cancer cell line MDA‐MB‐231 in vivo. Evid. Based Complement. Alternat. Med. 2020 2020 1 6823520 10.1155/2020/6823520 32714412
    [Google Scholar]
  85. Imenshahidi M. Hosseinzadeh H. Berberis vulgaris and berberine: An update review. Phytother. Res. 2016 30 11 1745 1764 10.1002/ptr.5693 27528198
    [Google Scholar]
  86. Liu Q. Xu X. Zhao M. Wei Z. Li X. Zhang X. Liu Z. Gong Y. Shao C. Berberine induces senescence of human glioblastoma cells by downregulating the EGFR-MEK-ERK signaling pathway. Mol. Cancer Ther. 2015 14 2 355 363 10.1158/1535‑7163.MCT‑14‑0634 25504754
    [Google Scholar]
  87. Chen Q. Shi J. Ding Z. Xia Q. Zheng T. Ren Y. Li M. Fan L. Berberine induces apoptosis in non-small-cell lung cancer cells by upregulating miR-19a targeting tissue factor. Cancer Manag. Res. 2019 11 9005 9015 10.2147/CMAR.S207677 31695492
    [Google Scholar]
  88. Fusi A. Festino L. Botti G. Masucci G. Melero I. Lorigan P. Ascierto P.A. PD-L1 expression as a potential predictive biomarker. Lancet Oncol. 2015 16 13 1285 1287 10.1016/S1470‑2045(15)00307‑1 26433815
    [Google Scholar]
  89. Liu Y. Liu X. Zhang N. Yin M. Dong J. Zeng Q. Mao G. Song D. Liu L. Deng H. Berberine diminishes cancer cell PD-L1 expression and facilitates antitumor immunity via inhibiting the deubiquitination activity of CSN5. Acta Pharm. Sin. B 2020 10 12 2299 2312 10.1016/j.apsb.2020.06.014 33354502
    [Google Scholar]
  90. Prajapati S.M. Patel K.D. Vekariya R.H. Panchal S.N. Patel H.D. Recent advances in the synthesis of quinolines: A review. RSC Advances 2014 4 47 24463 24476 10.1039/C4RA01814A
    [Google Scholar]
  91. Quinidine M. Encyclopedia of Toxicology. Elsevier 2014 16 18
    [Google Scholar]
  92. Qi Y. Pradipta A.R. Li M. Zhao X. Lu L. Fu X. Wei J. Hsung R.P. Tanaka K. Zhou L. Cinchonine induces apoptosis of HeLa and A549 cells through targeting TRAF6.. J Exp Clin Cancer Res. 2017 36 1 35
    [Google Scholar]
  93. Jayawickreme K. Świstak D. Ozimek E. Reszczyńska E. Rysiak A. Makuch-Kocka A. Hanaka A. Pyrrolizidine alkaloids—pros and cons for pharmaceutical and medical applications. Int. J. Mol. Sci. 2023 24 23 16972 10.3390/ijms242316972 38069294
    [Google Scholar]
  94. Cao R. Peng W. Wang Z. Xu A. beta-Carboline alkaloids: Biochemical and pharmacological functions. Curr. Med. Chem. 2007 14 4 479 500 10.2174/092986707779940998 17305548
    [Google Scholar]
  95. Tang J. Cao Y. Zhang H. Wang R. Oxymatrine inhibits the development of radioresistance in NSCLC cells by reversing EMT through the DcR3/AKT/GSK-3β pathway. Arch. Med. Sci. 2023 20 5
    [Google Scholar]
  96. Liu H. Zou M. Li P. Wang H. Lin X. Ye J. Oxymatrine‑mediated maturation of dendritic cells leads to activation of FOXP3+/CD4+ Treg cells and reversal of cisplatin‑resistance in lung cancer cells. Mol. Med. Rep. 2019 19 5 4081 4090 10.3892/mmr.2019.10064 30896871
    [Google Scholar]
  97. Manu K.A. Kuttan G. Anti-metastatic potential of punarnavine, an alkaloid from boerhaavia diffusa linn. Immunobiology 2009 214 4 245 255 10.1016/j.imbio.2008.10.002 19171408
    [Google Scholar]
  98. Saraswati S. Alhaider A.A. Agrawal S.S. Punarnavine, an alkaloid from Boerhaavia diffusa exhibits anti-angiogenic activity via downregulation of VEGF in vitro and in vivo. Chem Biol Interact. 2013 206 2 204 213
    [Google Scholar]
  99. Zheng L. Wang X. Luo W. Zhan Y. Zhang Y. Brucine, an effective natural compound derived from nux-vomica, induces G1 phase arrest and apoptosis in LoVo cells. Food Chem. Toxicol. 2013 58 332 339 10.1016/j.fct.2013.05.011 23688861
    [Google Scholar]
  100. Li M. Li P. Zhang M. Ma F. Su L. [Brucine inhibits the proliferation of human lung cancer cell line PC-9 
via arresting cell cycle]. Zhongguo Fei Ai Za Zhi 2014 17 6 444 450 24949683
    [Google Scholar]
  101. Rather R.A. Bhagat M. Cancer chemoprevention and piperine: Molecular mechanisms and therapeutic opportunities. Front. Cell Dev. Biol. 2018 6 6 10 10.3389/fcell.2018.00010 29497610
    [Google Scholar]
  102. Marques da Fonseca L. Jacques da Silva L.R. Santos dos Reis J. Rodrigues da Costa Santos M.A. de Sousa Chaves V. Monteiro da Costa K. Sa-Diniz J.N. Freire de Lima C.G. Morrot A. Nunes Franklim T. de Alcântara-Pinto D.C. Freire de Lima M.E. Previato J.O. Mendonça-Previato L. Freire-de-Lima L. Piperine inhibits TGF-β signaling pathways and disrupts emt-related events in human lung adenocarcinoma cells. Medicines (Basel) 2020 7 4 19 10.3390/medicines7040019 32276474
    [Google Scholar]
  103. Jeong J. H. Ryu J. H. Lee H. J. In vitro inhibition of Piper nigrum and piperine on growth, migration, and invasion of PANC-1 human pancreatic cancer cells. Natural Product Communications 2021 16 11 10.1177/1934578X211057694
    [Google Scholar]
  104. Zheng J. Zhou Y. Li Y. Xu D.P. Li S. Li H.B. Spices for prevention and treatment of cancers. Nutrients 2016 8 8 495 10.3390/nu8080495 27529277
    [Google Scholar]
  105. Sunil Kumar A. Kudva J. Lahtinen M. Peuronen A. Sadashiva R. Naral D. Synthesis, characterization, crystal structures and biological screening of 4-amino quinazoline sulfonamide derivatives. J. Mol. Struct. 2019 1190 29 36 10.1016/j.molstruc.2019.04.050
    [Google Scholar]
  106. Knight L.A. Di Nicolantonio F. Whitehouse P. Mercer S. Sharma S. Glaysher S. Johnson P. Cree I.A. The in vitroeffect of gefitinib (‘Iressa’) alone and in combination with cytotoxic chemotherapy on human solid tumours. BMC Cancer 2004 4 1 83 10.1186/1471‑2407‑4‑83 15560844
    [Google Scholar]
  107. Costanzo R. Piccirillo M.C. Sandomenico C. Carillio G. Montanino A. Daniele G. Giordano P. Bryce J. De Feo G. Di Maio M. Rocco G. Normanno N. Perrone F. Morabito A. Gefitinib in non small cell lung cancer. J. Biomed. Biotechnol. 2011 2011 815269 21660144
    [Google Scholar]
  108. Sun C. Gao W. Liu J. Cheng H. Hao J. FGL1 regulates acquired resistance to Gefitinib by inhibiting apoptosis in non-small cell lung cancer. Respir. Res. 2020 21 1 210 10.1186/s12931‑020‑01477‑y 32778129
    [Google Scholar]
  109. Li T. Qian Y. Zhang C. Uchino J. Provencio M. Wang Y. Shi X. Zhang Y. Zhang X. Anlotinib combined with gefitinib can significantly improve the proliferation of epidermal growth factor receptor-mutant advanced non-small cell lung cancer in vitro and in vivo. Transl. Lung Cancer Res. 2021 10 4 1873 1888 10.21037/tlcr‑21‑192 34012799
    [Google Scholar]
  110. Okita R. Shimizu K. Nojima Y. Yukawa T. Maeda A. Saisho S. Nakata M. Lapatinib enhances trastuzumab-mediated antibody-dependent cellular cytotoxicity via upregulation of HER2 in malignant mesothelioma cells. Oncol. Rep. 2015 34 6 2864 2870 10.3892/or.2015.4314 26503698
    [Google Scholar]
  111. Nelson V. Ziehr J. Agulnik M. Johnson M. Afatinib: Emerging next-generation tyrosine kinase inhibitor for NSCLC. OncoTargets Ther. 2013 6 135 143 23493883
    [Google Scholar]
  112. Lee S.H. Lee J.K. Ahn M.J. Kim D.W. Sun J.M. Keam B. Kim T.M. Heo D.S. Ahn J.S. Choi Y.L. Min H.S. Jeon Y.K. Park K. Vandetanib in pretreated patients with advanced non-small cell lung cancer-harboring RET rearrangement: A phase II clinical trial. Ann. Oncol. 2017 28 2 292 297 10.1093/annonc/mdw559 27803005
    [Google Scholar]
/content/journals/npj/10.2174/0122103155322306241021043330
Loading
/content/journals/npj/10.2174/0122103155322306241021043330
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test