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image of Citral-Loaded Self Nano-Emulsifying Drug Delivery System Suppresses Metastasis and Enhances Apoptosis in SW620 Colon Cancer Cells

Abstract

Introduction

The global incidence of colon cancer is rising, highlighting the need for complementary therapeutic approaches using natural products such as citral. A self-nano-emulsifying drug delivery system incorporated with citral (CIT-SNEDDS) was formulated, and prior studies have demonstrated its potent antiproliferative effects on colon cancer cell lines.

Materials and Methods

The apoptosis-inducing ability of CIT-SNEDDS treatment on SW620 cells was evaluated using Acridine Orange/Propidium Iodide (AO/PI) assay, Annexin V-FITC assay, and cell cycle analysis by flow cytometry. Scratch assay and migration, and invasion assays were performed to assess its anti-metastatic effects.

Results

The cytotoxicity assay results showed that SNEDDS with citral (CIT-SNEDDS) significantly reduced cell viability in a dose-dependent manner compared to free citral and SNEDDS without citral. Acridine orange/propidium iodide staining and Annexin V assay results confirmed apoptosis in CIT-SNEDDS-treated cells. Cell cycle analysis indicated that CIT-SNEDDS induced arrest at the S and G2/M phases, which may contribute to apoptosis initiation. The scratch and trans-well assays demonstrated a reduction in SW620 cell migration and invasion capabilities following CIT-SNEDDS treatment, suggesting a potent anti-metastatic effect.

Discussion

The ability of CIT-SNEDDS to induce apoptosis, disrupt the cell cycle, and inhibit cellular migration in cancer cells aligns with the goals of targeted cancer therapies, which aim to selectively eradicate cancer cells while minimizing effects on healthy tissue.

Conclusion

These findings highlight the therapeutic potential of CIT-SNEDDS for enhancing the efficacy of citral as an anti-tumor and antimetastatic agent for colorectal cancer, warranting further and preclinical studies to optimize its application.

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2026-01-09
2026-01-31
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References

  1. Gogoi P. Kaur G. Singh N.K. Nanotechnology for colorectal cancer detection and treatment. World J. Gastroenterol. 2022 28 46 6497 6511 10.3748/wjg.v28.i46.6497 36569271
    [Google Scholar]
  2. World Health Organization Colorectal cancer. 2023 Available from: https://www.who.int/news-room/fact-sheets/detail/colorectal-cancer#:~:text=Colon%20cancer%20is%20the%20second,individuals%20over%2050%20years%20old
  3. Sung H. Siegel R.L. Laversanne M. Jiang C. Morgan E. Zahwe M. Cao Y. Bray F. Jemal A. Colorectal cancer incidence trends in younger versus older adults: An analysis of population-based cancer registry data. Lancet Oncol. 2024 26 1 51 63 10.1016/S1470‑2045(24)00600‑4 39674189
    [Google Scholar]
  4. Pardamean C.I. Sudigyo D. Budiarto A. Mahesworo B. Hidayat A.A. Baurley J.W. Pardamean B. Changing colorectal cancer trends in Asians: Epidemiology and risk factors. Oncol. Rev. 2023 17 10576 10.3389/or.2023.10576 37284188
    [Google Scholar]
  5. Ministry of Health Malaysia National strategic plan for colorectal cancer 2021-2025. Available from: https://www.moh.gov.my/moh/resources/Penerbitan/Rujukan/NCD/Kanser/National_Strategic_Plan_for_Colorectal_Cancer_(NSPCRC)_2021-2025.pdf 2021
  6. Muhamad N.A. Ma’amor N.H. Rosli I.A. Leman F.N. Abdul Mutalip M.H. Chan H.K. Yusof S.N. Tamin N.S.I. Aris T. Lai N.M. Abu Hassan M.R. Colorectal cancer survival among Malaysia population: Data from the Malaysian National Cancer Registry. Front. Oncol. 2023 13 1132417 10.3389/fonc.2023.1132417 38094603
    [Google Scholar]
  7. Abu Hassan M.R. Ismail I. Mohd Suan M.A. Ahmad F. Wan Khazim W.K. Othman Z. Mat Said R. Tan W.L. Mohammed S.R.N.S. Soelar S.A. Nik Mustapha N.R. Incidence and mortality rates of colorectal cancer in Malaysia. Epidemiol. Health 2016 38 e2016007 10.4178/epih.e2016007 26971697
    [Google Scholar]
  8. Wang N. Chen L. Huang W. Gao Z. Jin M. Current advances of nanomaterial-based oral drug delivery for colorectal cancer treatment. Nanomaterials 2024 14 7 557 10.3390/nano14070557 38607092
    [Google Scholar]
  9. Menon G. Cagir B. Colon cancer. StatPearls StatPearls Publishing Treasure Island 2025
    [Google Scholar]
  10. Kumar A. Gautam V. Sandhu A. Rawat K. Sharma A. Saha L. Current and emerging therapeutic approaches for colorectal cancer: A comprehensive review. World J. Gastrointest. Surg. 2023 15 4 495 519 10.4240/wjgs.v15.i4.495 37206081
    [Google Scholar]
  11. Fadlallah H. El Masri J. Fakhereddine H. Youssef J. Chemaly C. Doughan S. Abou-Kheir W. Colorectal cancer: Recent advances in management and treatment. World J. Clin. Oncol. 2024 15 9 1136 1156 10.5306/wjco.v15.i9.1136 39351451
    [Google Scholar]
  12. Mohamed Abdoul-Latif F. Ainane A. Houmed Aboubaker I. Mohamed J. Ainane T. Exploring the potent anticancer activity of essential oils and their bioactive compounds: Mechanisms and prospects for future cancer therapy. Pharmaceuticals 2023 16 8 1086 10.3390/ph16081086 37631000
    [Google Scholar]
  13. Chunarkar-Patil P. Kaleem M. Mishra R. Ray S. Ahmad A. Verma D. Bhayye S. Dubey R. Singh H. Kumar S. Anticancer drug discovery based on natural products: From computational approaches to clinical studies. Biomedicines 2024 12 1 201 10.3390/biomedicines12010201 38255306
    [Google Scholar]
  14. Atanasov A.G. Zotchev S.B. Dirsch V.M. Orhan I.E. Banach M. Rollinger J.M. Barreca D. Weckwerth W. Bauer R. Bayer E.A. Majeed M. Bishayee A. Bochkov V. Bonn G.K. Braidy N. Bucar F. Cifuentes A. D’Onofrio G. Bodkin M. Diederich M. Dinkova-Kostova A.T. Efferth T. El Bairi K. Arkells N. Fan T-P. Fiebich B.L. Freissmuth M. Georgiev M.I. Gibbons S. Godfrey K.M. Gruber C.W. Heer J. Huber L.A. Ibanez E. Kijjoa A. Kiss A.K. Lu A. Macias F.A. Miller M.J.S. Mocan A. Müller R. Nicoletti F. Perry G. Pittalà V. Rastrelli L. Ristow M. Russo G.L. Silva A.S. Schuster D. Sheridan H. Skalicka-Woźniak K. Skaltsounis L. Sobarzo-Sánchez E. Bredt D.S. Stuppner H. Sureda A. Tzvetkov N.T. Vacca R.A. Aggarwal B.B. Battino M. Giampieri F. Wink M. Wolfender J-L. Xiao J. Yeung A.W.K. Lizard G. Popp M.A. Heinrich M. Berindan-Neagoe I. Stadler M. Daglia M. Verpoorte R. Supuran C.T. Natural products in drug discovery: Advances and opportunities. Nat. Rev. Drug Discov. 2021 20 3 200 216 10.1038/s41573‑020‑00114‑z 33510482
    [Google Scholar]
  15. Hui Z. Wen H. Zhu J. Deng H. Jiang X. Ye X.Y. Wang L. Xie T. Bai R. Discovery of plant-derived anti-tumor natural products: Potential leads for anti-tumor drug discovery. Bioorg. Chem. 2024 142 106957 10.1016/j.bioorg.2023.106957 37939507
    [Google Scholar]
  16. Asma S.T. Acaroz U. Imre K. Morar A. Shah S.R.A. Hussain S.Z. Arslan-Acaroz D. Demirbas H. Hajrulai-Musliu Z. Istanbullugil F.R. Soleimanzadeh A. Morozov D. Zhu K. Herman V. Ayad A. Athanassiou C. Ince S. Natural products/bioactive compounds as a source of anticancer drugs. Cancers 2022 14 24 6203 10.3390/cancers14246203 36551687
    [Google Scholar]
  17. Idrees M. Hakkim F.L. Naikoo G.A. Hassan I.U. Recent advances in extraction, characterization, and potential use of citral. Natural Bio-active Compounds Springer Singapore 2019 225 236 10.1007/978‑981‑13‑7438‑8_9
    [Google Scholar]
  18. Pucci M. Raimondo S. Zichittella C. Tinnirello V. Corleone V. Aiello G. Moschetti M. Conigliaro A. Fontana S. Alessandro R. Biological properties of a citral-enriched fraction of Citrus limon essential oil. Foods 2020 9 9 1290 10.3390/foods9091290 32937843
    [Google Scholar]
  19. Green M. Citral: Behind a component of lemongrass oil. 2019 Available from: http://terpenesandtesting. com/category/science/citral-behind-a-component-of-lemongrass-oil/
  20. Team E.W. CHEBI:23316 - citral. 2018 Available from: https://www.ebi.ac.uk/chebi/searchId.do;jsessionid=DDBED692BD86179A9F78615B68667B1F?chebiId=23316&structureView=applet&viewTermLineage=
  21. Sharma S. Perera K.Y. Jaiswal A.K. Jaiswal S. Natural antimicrobials from fruits and plant extract for food packaging and preservation. Food Packaging and Preservation Academic Press 2024 133 152 10.1016/B978‑0‑323‑90044‑7.00008‑2
    [Google Scholar]
  22. Nagata T. Satou T. Hayashi S. Satyal P. Watanabe M. Riggs B. Saida Y. Citral in lemon myrtle, lemongrass, litsea, and melissa essential oils suppress the growth and invasion of breast cancer cells. BMC Complement. Med. Ther. 2024 24 1 211 10.1186/s12906‑024‑04511‑4 38831283
    [Google Scholar]
  23. Srivastava G. Mukherjee E. Mittal R. Ganjewala D. Geraniol and citral: Recent developments in their anticancer credentials opening new vistas in complementary cancer therapy. Z. Naturforsch. C J. Biosci. 2024 79 7-8 163 177 10.1515/znc‑2023‑0150 38635829
    [Google Scholar]
  24. Sharma S. Habib S. Sahu D. Gupta J. Chemical properties and therapeutic potential of citral, a monoterpene isolated from lemongrass. Med. Chem. 2021 17 1 2 12 10.2174/18756638MTAzbMjYa2 31880247
    [Google Scholar]
  25. Ashaq B. Rasool K. Habib S. Bashir I. Nisar N. Mustafa S. Ayaz Q. Nayik G.A. Uddin J. Ramniwas S. Mugabi R. Wani S.M. Insights into chemistry, extraction and industrial application of lemon grass essential oil -A review of recent advances. Food Chem. X 2024 22 101521 10.1016/j.fochx.2024.101521 38952570
    [Google Scholar]
  26. Mohd Izham M.N. Hussin Y. Aziz M.N.M. Yeap S.K. Rahman H.S. Masarudin M.J. Mohamad N.E. Abdullah R. Alitheen N.B. Preparation and characterization of self nano-emulsifying drug delivery system loaded with citraland its antiproliferative effect on colorectal cells in vitro. Nanomaterials 2019 9 7 1028 10.3390/nano9071028 31323842
    [Google Scholar]
  27. Nordin N. Yeap S.K. Rahman H.S. Zamberi N.R. Abu N. Mohamad N.E. How C.W. Masarudin M.J. Abdullah R. Alitheen N.B. In vitro cytotoxicity and anticancer effects of citral nanostructured lipid carrier on MDA MBA-231 human breast cancer cells. Sci. Rep. 2019 9 1 1614 10.1038/s41598‑018‑38214‑x 30733560
    [Google Scholar]
  28. Kawish S.M. Sharma S. Gupta P. Ahmad F.J. Iqbal M. Alshabrmi F.M. Anwer M.K. Fathi-karkan S. Rahdar A. Aboudzadeh M.A. Nanoparticle-Based Drug delivery Platform for simultaneous administration of phytochemicals and chemotherapeutics: Emerging trends in cancer management. Part. Part. Syst. Charact. 2024 41 12 2400049 10.1002/ppsc.202400049
    [Google Scholar]
  29. Mukhtar M.H. El-Readi M.Z. Elzubier M.E. Fatani S.H. Refaat B. Shaheen U. Adam Khidir E.B. Taha H.H. Eid S.Y. Cymbopogon citratus and citral overcome doxorubicin resistance in cancer cells via modulating the drug’s metabolism, toxicity, and multidrug transporters. Molecules 2023 28 8 3415 10.3390/molecules28083415 37110649
    [Google Scholar]
  30. Lima T.S. Silva M.F.S. Nunes X.P. Colombo A.V. Oliveira H.P. Goto P.L. Blanzat M. Piva H.L. Tedesco A.C. Siqueira-Moura M.P. Cineole-containing nanoemulsion: Development, stability, and antibacterial activity. Chem. Phys. Lipids 2021 239 105113 10.1016/j.chemphyslip.2021.105113 34216586
    [Google Scholar]
  31. Chauhan A. Kamal R. Mishra R. Shekho D. Awasthi A. A comprehensive guide to the development, evaluation, and future prospects of self-nanoemulsifying drug delivery systems for poorly water-soluble drugs. Curr. Pharm. Des. 2024 30 16 1211 1216 10.2174/0113816128296705240327065131 38584540
    [Google Scholar]
  32. Wu F. Ma Q. Tian G. Chen K. Yang R. Shen J. Formulation and evaluation of solid self-nanoemulsifying drug delivery system of cannabidiol for enhanced solubility and bioavailability. Pharmaceutics 2025 17 3 340 10.3390/pharmaceutics17030340 40143004
    [Google Scholar]
  33. Kazi M. Al-Swairi M. Ahmad A. Raish M. Alanazi F.K. Badran M.M. Khan A.A. Alanazi A.M. Hussain M.D. Evaluation of self-nanoemulsifying drug delivery systems (SNEDDS) for poorly water-soluble talinolol: Preparation, in vitro and in vivo assessment. Front. Pharmacol. 2019 10 459 10.3389/fphar.2019.00459 31118895
    [Google Scholar]
  34. Buya A.B. Beloqui A. Memvanga P.B. Préat V. Self- nano-emulsifying drug-delivery systems: From the development to the current applications and challenges in oral drug delivery. Pharmaceutics 2020 12 12 1194 10.3390/pharmaceutics12121194 33317067
    [Google Scholar]
  35. Astuti I.Y. Marchaban M. Martien R. Nugroho A.E. Design and optimization of self nano-emulsifying drug delivery system containing a new anti-inflamatory agent pentagamavunon-0. Indones. J. Chem. 2017 17 3 365 10.22146/ijc.22640
    [Google Scholar]
  36. D S. Prasanna J L. A literature review on self nanoemulsifying drug delivery system (SNEDDS). Int. J. Pharm. Sci. Rev. Res. 2021 70 1 10.47583/ijpsrr.2021.v70i01.011
    [Google Scholar]
  37. SW620 SW-620 2024 Available from: https://www.atcc.org/products/ccl-227
  38. Slater C. de La Mare J.A. Edkins A. In vitro analysis of putative cancer stem cell populations and chemosensitivity in the SW480 and SW620 colon cancer metastasis model. Oncol. Lett. 2018 15 6 8516 8526 10.3892/ol.2018.8431 29805588
    [Google Scholar]
  39. Zhu Q. Meisinger J. Thiel D.H.V. Zhang Y. Mobarhan S. Effects of soybean extract on morphology and survival of Caco-2, SW620, and HT-29 cells. Nutr. Cancer 2002 42 1 131 140 10.1207/S15327914NC421_18 12235645
    [Google Scholar]
  40. Omary M.B. de Grandpre L. McCaffrey M. Kagnoff M.F. Biochemical and morphological differentiation of the human colonic epithelial cell line SW620 in the presence of dimethylsulfoxide. J. Cell. Biochem. 1992 48 3 316 323 10.1002/jcb.240480312 1400616
    [Google Scholar]
  41. Ji Z. Tang Q. Hao R. Zhang J. Pan Y. Induction of apoptosis in the SW620 colon carcinoma cell line by triterpene-enriched extracts from Ganoderma lucidum through activation of caspase-3. Oncol. Lett. 2011 2 3 565 570 10.3892/ol.2011.275 22866120
    [Google Scholar]
  42. Ismail N. Ismail M. Imam M.U. Azmi N.H. Fathy S.F. Foo J.B. Abu Bakar M.F. Mechanistic basis for protection of differentiated SH-SY5Y cells by oryzanol-rich fraction against hydrogen peroxide-induced neurotoxicity. BMC Complement. Altern. Med. 2014 14 1 467 10.1186/1472‑6882‑14‑467 25475556
    [Google Scholar]
  43. Rahim N.F.C. Hussin Y. Aziz M.N.M. Mohamad N.E. Yeap S.K. Masarudin M.J. Abdullah R. Akhtar M.N. Alitheen N.B. Cytotoxicity and apoptosis effects of curcumin analogue (2E,6E)-2,6-Bis(2,3-Dimethoxybenzylidine) cyclohexanone (DMCH) on human colon cancer cells HT29 and SW620 in vitro. Molecules 2021 26 5 1261 10.3390/molecules26051261 33652694
    [Google Scholar]
  44. Izham M.N.M. Hussin Y. Rahim N.F.C. Aziz M.N.M. Yeap S.K. Rahman H.S. Masarudin M.J. Mohamad N.E. Abdullah R. Alitheen N.B. Physicochemical characterization, cytotoxic effect and toxicity evaluation of nanostructured lipid carrier loaded with eucalyptol. BMC Complement. Med. Ther. 2021 21 1 254 10.1186/s12906‑021‑03422‑y 34620132
    [Google Scholar]
  45. Hussin Y. Aziz M. Che Rahim N. Yeap S. Mohamad N. Masarudin M. Nordin N. Abd Rahman N. Yong C. Akhtar M. Zamrus S. Alitheen N. DK1 induces apoptosis via mitochondria-dependent signaling pathway in human colon carcinoma cell lines in vitro. Int. J. Mol. Sci. 2018 19 4 1151 10.3390/ijms19041151 29641445
    [Google Scholar]
  46. Juan T.K. Liu K.C. Kuo C.L. Yang M.D. Chu Y.L. Yang J.L. Wu P.P. Huang Y.P. Lai K.C. Chung J.G. Tetrandrine suppresses adhesion, migration and invasion of human colon cancer SW620 cells via inhibition of nuclear factor-κB, matrix metalloproteinase-2 and matrix metalloproteinase-9 signaling pathways. Oncol. Lett. 2018 15 5 7716 7724 10.3892/ol.2018.8286 29731901
    [Google Scholar]
  47. Aziz M.N.M. Rahim N.F.C. Hussin Y. Yeap S.K. Masarudin M.J. Mohamad N.E. Akhtar M.N. Osman M.A. Cheah Y.K. Alitheen N.B. Anti-metastatic and anti-angiogenic effects of curcumin analog DK1 on human osteosarcoma cells in vitro. Pharmaceuticals 2021 14 6 532 10.3390/ph14060532 34204873
    [Google Scholar]
  48. Schaeffer D. Somarelli J.A. Hanna G. Palmer G.M. Garcia-Blanco M.A. Cellular migration and invasion uncoupled: Increased migration is not an inexorable consequence of epithelial-to-mesenchymal transition. Mol. Cell. Biol. 2014 34 18 3486 3499 10.1128/MCB.00694‑14 25002532
    [Google Scholar]
  49. Justus C.R. Marie M.A. Sanderlin E.J. Yang L.V. Transwell in vitro cell migration and invasion assays. Methods Mol. Biol. 2023 2644 349 359 10.1007/978‑1‑0716‑3052‑5_22 37142933
    [Google Scholar]
  50. Pijuan J. Barceló C. Moreno D.F. Maiques O. Sisó P. Marti R.M. Macià A. Panosa A. In vitro cell migration, invasion, and adhesion assays: From cell imaging to data analysis. Front. Cell Dev. Biol. 2019 7 107 10.3389/fcell.2019.00107 31259172
    [Google Scholar]
  51. Preeti N. Sambhakar S. Malik R. Bhatia S. Al Harrasi A. Rani C. Saharan R. Kumar S. Geeta Sehrawat R. Nanoemulsion: An emerging novel technology for improving the bioavailability of drugs. Scientifica 2023 2023 1 25 10.1155/2023/6640103 37928749
    [Google Scholar]
  52. Chavda V.P. Patel A.B. Mistry K.J. Suthar S.F. Wu Z.X. Chen Z.S. Hou K. Nano-Drug delivery systems entrapping natural bioactive compounds for cancer: Recent progress and future challenges. Front. Oncol. 2022 12 867655 10.3389/fonc.2022.867655 35425710
    [Google Scholar]
  53. Srivastava S. Haider M.F. Ahmad A. Ahmad U. Arif M. Ali A. Exploring nanoemulsions for prostate cancer therapy. Drug Res. 2021 71 8 417 428 10.1055/a‑1518‑6606 34157752
    [Google Scholar]
  54. Akhtar N. Mohammed S.A.A. Khan R.A. Yusuf M. Singh V. Mohammed H.A. Al-Omar M.S. Abdellatif A.A.H. Naz M. Khadri H. Self-Generating nano-emulsification techniques for alternatively-routed, bioavailability enhanced delivery, especially for anti-cancers, anti-diabetics, and miscellaneous drugs of natural, and synthetic origins. J. Drug Deliv. Sci. Technol. 2020 58 101808 10.1016/j.jddst.2020.101808
    [Google Scholar]
  55. Paul S. Hmar E.B.L. Zothantluanga J.H. Sharma H.K. Essential oils: A review on their salient biological activities and major delivery strategies. Sci. Vis. 2020 20 2 54 71 10.33493/scivis.20.02.01
    [Google Scholar]
  56. Kassem A.A. Abd El-Alim S.H. Salman A.M. Mohammed M.A. Hassan N.S. El-Gengaihi S.E. Improved hepatoprotective activity of Beta vulgaris L. leaf extract loaded self-nanoemulsifying drug delivery system (SNEDDS): In vitro in vivo evaluation. Drug Dev. Ind. Pharm. 2020 46 10 1589 1603 10.1080/03639045.2020.1811303 32811211
    [Google Scholar]
  57. Gutiérrez-Pacheco M.M. Torres-Moreno H. Flores-Lopez M.L. Velázquez Guadarrama N. Ayala-Zavala J.F. Ortega-Ramírez L.A. López-Romero J.C. Mechanisms and applications of Citral’s antimicrobial properties in food preservation and pharmaceuticals formulations. Antibiotics 2023 12 11 1608 10.3390/antibiotics12111608 37998810
    [Google Scholar]
  58. Kumari S. Goyal A. Sönmez Gürer E. Algın Yapar E. Garg M. Sood M. Sindhu R.K. Bioactive loaded novel nano-formulations for targeted drug delivery and their therapeutic potential. Pharmaceutics 2022 14 5 1091 10.3390/pharmaceutics14051091 35631677
    [Google Scholar]
  59. Nordin N. Yeap S.K. Rahman H.S. Zamberi N.R. Mohamad N.E. Abu N. Masarudin M.J. Abdullah R. Alitheen N.B. Antitumor and anti-metastatic effects of citral-loaded nanostructured lipid carrier in 4T1-induced breast cancer mouse model. Molecules 2020 25 11 2670 10.3390/molecules25112670 32526880
    [Google Scholar]
  60. Krishna G. Thrimothi D. Nano emulsions: A novel targeted delivery of cancer therapeutics. Design and Applications of Self-Assembly Aggregates - From Micelles to Nanoemulsions IntechOpen 2024 10.5772/intechopen.1004748
    [Google Scholar]
  61. Neophytou C.M. Gregoriou Y. Constantinou A.I. Pro-apoptotic properties of chemopreventive agents. Natural Products for Cancer Chemoprevention Springer 2020 517 559 10.1007/978‑3‑030‑39855‑2_16
    [Google Scholar]
  62. Samia S. Sandeep Chary P. Khan O. Kumar Mehra N. Recent trends and advances in novel formulations as an armament in Bcl-2/Bax targeted breast cancer. Int. J. Pharm. 2024 653 123889 10.1016/j.ijpharm.2024.123889 38346605
    [Google Scholar]
  63. Pahwa R. Sharma G. Chhabra J. Haider T. Anitha K. Mishra N. Nanoemulsion therapy: A paradigm shift in lung cancer management. J. Drug Deliv. Sci. Technol. 2024 101 106227 10.1016/j.jddst.2024.106227
    [Google Scholar]
  64. Sheikh B.Y. Sarker M.M.R. Kamarudin M.N.A. Mohan G. Antiproliferative and apoptosis inducing effects of citral via p53 and ROS-induced mitochondrial-mediated apoptosis in human colorectal HCT116 and HT29 cell lines. Biomed. Pharmacother. 2017 96 834 846 10.1016/j.biopha.2017.10.038 29078261
    [Google Scholar]
  65. Chaouki W. Leger D.Y. Liagre B. Beneytout J.L. Hmamouchi M. Citral inhibits cell proliferation and induces apoptosis and cell cycle arrest in MCF-7 cells. Fundam. Clin. Pharmacol. 2009 23 5 549 556 10.1111/j.1472‑8206.2009.00738.x 19656204
    [Google Scholar]
  66. Kapur A. Felder M. Fass L. Kaur J. Czarnecki A. Rathi K. Zeng S. Osowski K.K. Howell C. Xiong M.P. Whelan R.J. Patankar M.S. Modulation of oxidative stress and subsequent induction of apoptosis and endoplasmic reticulum stress allows citral to decrease cancer cell proliferation. Sci. Rep. 2016 6 1 27530 10.1038/srep27530 27270209
    [Google Scholar]
  67. Luk S.C.W. Siu S.W.F. Lai C.K. Wu Y.J. Pang S.F. Cell cycle arrest by a natural product via G2/M checkpoint. Int. J. Med. Sci. 2005 2 2 64 69 10.7150/ijms.2.64 15968342
    [Google Scholar]
  68. Lu W.C. Huang D.W. Wang C.C.R. Yeh C.H. Tsai J.C. Huang Y.T. Li P.H. Preparation, characterization, and antimicrobial activity of nanoemulsions incorporating citral essential oil. J. Food Drug Anal. 2018 26 1 82 89 10.1016/j.jfda.2016.12.018 29389592
    [Google Scholar]
  69. McClements D.J. Rao J. Food-grade nanoemulsions: Formulation, fabrication, properties, performance, biological fate, and potential toxicity. Crit. Rev. Food Sci. Nutr. 2011 51 4 285 330 10.1080/10408398.2011.559558 21432697
    [Google Scholar]
  70. Sharma P. Chaturvedi S. Khan M.A. Rai Y. Bhatt A.N. Najmi A.K. Akhtar M. Mishra A.K. Nanoemulsion potentiates the anti-cancer activity of Myricetin by effective inhibition of PI3K/AKT/mTOR pathway in triple-negative breast cancer cells. Med. Oncol. 2024 41 2 56 10.1007/s12032‑023‑02274‑5 38218749
    [Google Scholar]
  71. He Y. Sun M.M. Zhang G.G. Yang J. Chen K.S. Xu W.W. Li B. Targeting PI3K/Akt signal transduction for cancer therapy. Signal Transduct. Target. Ther. 2021 6 1 425 10.1038/s41392‑021‑00828‑5 34916492
    [Google Scholar]
  72. Bailly C. Targets and pathways involved in the antitumor activity of citral and its stereo-isomers. Eur. J. Pharmacol. 2020 871 172945 10.1016/j.ejphar.2020.172945 31981590
    [Google Scholar]
  73. Islam M.T. Jang N.H. Lee H.J. Natural products as regulators against matrix metalloproteinases for the treatment of cancer. Biomedicines 2024 12 4 794 10.3390/biomedicines12040794 38672151
    [Google Scholar]
  74. Quintero-Fabián S. Arreola R. Becerril-Villanueva E. Torres-Romero J.C. Arana-Argáez V. Lara-Riegos J. Ramírez-Camacho M.A. Alvarez-Sánchez M.E. Role of matrix metalloproteinases in angiogenesis and Cancer. Front. Oncol. 2019 9 1370 10.3389/fonc.2019.01370 31921634
    [Google Scholar]
  75. Dienstmann R. Rodon J. Tabernero J. Cancer treatment in the era of personalized medicine: A paradigm shift in drug development and clinical trials. Cancer Discov. 2013 3 12 1332 1342 10.1158/2159‑8290.CD‑13‑0344
    [Google Scholar]
  76. Shin A.E. Giancotti F.G. Rustgi A.K. Metastatic colorectal cancer: Mechanisms and emerging therapeutics. Trends Pharmacol. Sci. 2023 44 4 222 236 10.1016/j.tips.2023.01.003 36828759
    [Google Scholar]
  77. Li F. Lin Y. Li R. Shen X. Xiang M. Xiong G. Zhang K. Xia T. Guo J. Miao Z. Liao Y. Zhang X. Xie L. Molecular targeted therapy for metastatic colorectal cancer: Current and evolving approaches. Front. Pharmacol. 2023 14 1165666 10.3389/fphar.2023.1165666 37927605
    [Google Scholar]
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