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image of Therapeutic Effects of Crocin Nanoparticles Alone or in Combination with Doxorubicin against Hepatocellular Carcinoma In vitro

Abstract

Objective

Crocin (CRO), the primary antioxidant in saffron, is known for its anticancer properties. However, its effectiveness in topical therapy is limited due to low bioavailability, poor absorption, and low physicochemical stability. This study aimed to prepare crocin nanoparticles (CRO-NPs) to enhance their pharmaceutical efficacy and evaluate the synergistic effects of Cro-NPs with doxorubicin (DOX) chemotherapy on two cell lines: human hepatocellular carcinoma cells (HepG2) and non-cancerous cells (WI38).

Methods

CRO-NPs were prepared using the emulsion diffusion technique and characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), Zeta potential, and Fourier transform infrared spectroscopy (FT-IR). Cell proliferation inhibition was assessed using the MTT assay for DOX, CRO, CRO-NPs, and DOX+CRO-NPs. Apoptosis and cell cycle were evaluated by flow cytometry, and changes in the expression of apoptotic gene (P53) and autophagic genes (ATG5 & LC3) were analyzed using real-time polymerase chain reaction.

Results

TEM and SEM revealed that CRO-NPs exhibited a relatively spherical shape with an average size of 9.3 nm, and zeta potential analysis indicated better stability of CRO-NPs compared to native CRO. Significantly higher antitumor effects of CRO-NPs were observed against HepG2 cells (IC = 1.1 mg/ml and 0.57 mg/ml) compared to native CRO (IC = 6.1 mg/ml and 3.2 mg/ml) after 24 and 48 hours, respectively. Annexin-V assay on HepG2 cells indicated increased apoptotic rates across all treatments, with the highest percentage observed in CRO-NPs, accompanied by cell cycle arrest at the G2/M phase. Furthermore, gene expression analysis showed upregulation of P53, ATG5, and LC3 genes in DOX/CRO-NPs co-treatment compared to individual treatments. In contrast, WI38 cells exhibited greater sensitivity to DOX toxicity but showed no adverse response to CRO-NPs.

Conclusion

Although more studies in animal models are required to corroborate these results, our findings suggest that CRO-NPs can be a potential new anticancer agent for hepatocellular carcinoma. Moreover, they have a synergistic effect with DOX against HepG2 cells and mitigate the toxicity of DOX on normal WI38 cells.

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2024-10-09
2024-12-04

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References

  1. Serra M. Di Matteo M. Serneels J. Pal R. Cafarello S.T. Lanza M. Sanchez-Martin C. Evert M. Castegna A. Calvisi D.F. Mazzone M. Columbano A. Deletion of Lactate Dehydrogenase-A Impairs Oncogene-Induced Mouse Hepatocellular Carcinoma Development. Cell. Mol. Gastroenterol. Hepatol. 2022 14 3 609 624 10.1016/j.jcmgh.2022.06.003 35714859
    [Google Scholar]
  2. Abdu S. Juaid N. Amin A. Moulay M. Miled N. Therapeutic Effects of Crocin Alone or in Combination with Sorafenib against Hepatocellular Carcinoma: In Vivo & In Vitro Insights. Antioxidants 2022 11 9 1645 10.3390/antiox11091645 36139719
    [Google Scholar]
  3. Singal A.G. Kanwal F. Llovet J.M. Global trends in hepatocellular carcinoma epidemiology: implications for screening, prevention and therapy. Nat. Rev. Clin. Oncol. 2023 20 12 864 884 10.1038/s41571‑023‑00825‑3 37884736
    [Google Scholar]
  4. Serraino D. Fratino L. Piselli P. Epidemiological Aspects of Hepatocellular Carcinoma. Hepatocellular Carcinoma. Ettorre G.M. [Internet] Cham Springer International Publishing 2023 3 9 10.1007/978‑3‑031‑09371‑5_1
    [Google Scholar]
  5. Toh M.R. Wong E.Y.T. Wong S.H. Ng A.W.T. Loo L.H. Chow P.K.H. Ngeow J. Global Epidemiology and Genetics of Hepatocellular Carcinoma. Gastroenterology 2023 164 5 766 782 10.1053/j.gastro.2023.01.033 36738977
    [Google Scholar]
  6. Kim D.Y. Changing etiology and epidemiology of hepatocellular carcinoma: Asia and worldwide. J. Liver Cancer 2024 24 1 622 670 10.17998/jlc.2024.03.13 38523466
    [Google Scholar]
  7. Epidemiology and risk factors for hepatocellular carcinoma. 2024 Available from: https://www.uptodate.com/contents/epidemiology-and-risk-factors-for-hepatocellular-carcinoma/print(accessed on 7-8-2024)
  8. Reddy K.R. McLerran D. Marsh T. Parikh N. Roberts L.R. Schwartz M. Nguyen M.H. Befeler A. Page-Lester S. Tang R. Srivastava S. Rinaudo J.A. Feng Z. Marrero J.A. Incidence and Risk Factors for Hepatocellular Carcinoma in Cirrhosis: The Multicenter Hepatocellular Carcinoma Early Detection Strategy (HEDS) Study. Gastroenterology 2023 165 4 1053 1063.e6 10.1053/j.gastro.2023.06.027 37429366
    [Google Scholar]
  9. Shannon A.H. Ruff S.M. Pawlik T.M. Expert Insights on Current Treatments for Hepatocellular Carcinoma: Clinical and Molecular Approaches and Bottlenecks to Progress. J. Hepatocell. Carcinoma 2022 9 1247 1261 10.2147/JHC.S383922 36514693
    [Google Scholar]
  10. Villarruel-Melquiades F. Mendoza-Garrido M.E. García-Cuellar C.M. Sánchez-Pérez Y. Pérez-Carreón J.I. Camacho J. Current and novel approaches in the pharmacological treatment of hepatocellular carcinoma. World J. Gastroenterol. 2023 29 17 2571 2599 10.3748/wjg.v29.i17.2571 37213397
    [Google Scholar]
  11. Al-Hrout A. Chaiboonchoe A. Khraiwesh B. Murali C. Baig B. El-Awady R. Tarazi H. Alzahmi A. Nelson D.R. Greish Y.E. Ramadan W. Salehi-Ashtiani K. Amin A. Safranal induces DNA double-strand breakage and ER-stress-mediated cell death in hepatocellular carcinoma cells. Sci. Rep. 2018 8 1 16951 10.1038/s41598‑018‑34855‑0 30446676
    [Google Scholar]
  12. Ntellas P. Chau I. Updates on Systemic Therapy for Hepatocellular Carcinoma. Am. Soc. Clin. Oncol. Educ. Book 2024 44 1 e430028 10.1200/EDBK_430028 38175973
    [Google Scholar]
  13. Zhu C. Zhao M. Fan L. Cao X. Xia Q. Zhou J. Yin H. Zhao L. Chitopentaose inhibits hepatocellular carcinoma by inducing mitochondrial mediated apoptosis and suppressing protective autophagy. Bioresour. Bioprocess. 2021 8 1 4 10.1186/s40643‑020‑00358‑y 38650195
    [Google Scholar]
  14. Cao C. Li Y. Shi F. Jiang S. Li Y. Yang L. Zhou X. Gao Y. Tang F. Li H. Han S. Yu Z. Zou Y. Guo J. Nano co-delivery of doxorubicin and plumbagin achieves synergistic chemotherapy of hepatocellular carcinoma. Int. J. Pharm. 2024 661 124424 10.1016/j.ijpharm.2024.124424 38971510
    [Google Scholar]
  15. Qin Y. Wang C.J. Ye H.L. Ye G.X. Wang S. Pan D.B. Wang J. Shen H.J. Xu S.Q. WWP2 overexpression inhibits the antitumor effects of doxorubicin in hepatocellular carcinoma. Cell Biol. Int. 2022 46 10 1682 1692 10.1002/cbin.11856 35880837
    [Google Scholar]
  16. Li CJ. Tsai HW. Chen YL. Wang CI. Lin YH. Chu PM. Cisplatin or doxorubicin reduces cell viability via the PTPIVA3-JAK2-STAT3 cascade in hepatocellular carcinoma. J Hepatocell Carcinoma. 2023 10 123 138
    [Google Scholar]
  17. Kullenberg F. Degerstedt O. Calitz C. Pavlović N. Balgoma D. Gråsjö J. Sjögren E. Hedeland M. Heindryckx F. Lennernäs H. In vitro cell toxicity and intracellular uptake of doxorubicin exposed as a solution or liposomes: implications for treatment of hepatocellular carcinoma. Cells 2021 10 7 1717 10.3390/cells10071717 34359887
    [Google Scholar]
  18. Sun J.B. Duan J.H. Dai S.L. Ren J. Zhang Y.D. Tian J.S. Li Y. In vitro and in vivo antitumor effects of doxorubicin loaded with bacterial magnetosomes (DBMs) on H22 cells: The magnetic bio-nanoparticles as drug carriers. Cancer Lett. 2007 258 1 109 117 10.1016/j.canlet.2007.08.018 17920762
    [Google Scholar]
  19. Khafaga A.F. El-Sayed Y.S. All-trans-retinoic acid ameliorates doxorubicin-induced cardiotoxicity: in vivo potential involvement of oxidative stress, inflammation, and apoptosis via caspase-3 and p53 down-expression. Naunyn Schmiedebergs Arch. Pharmacol. 2018 391 1 59 70 10.1007/s00210‑017‑1437‑5 29085977
    [Google Scholar]
  20. Afsar T. Razak S. Almajwal A. Effect of Acacia hydaspica R. Parker extract on lipid peroxidation, antioxidant status, liver function test and histopathology in doxorubicin treated rats. Lipids Health Dis. 2019 18 1 126 10.1186/s12944‑019‑1051‑2 31142345
    [Google Scholar]
  21. Block KI. Gyllenhaal C. Lowe L. Amedei A. Amin ARMR. Amin A. Designing a broad-spectrum integrative approach for cancer prevention and treatment. Semin Cancer Biol. 2015 35 S276 S304 10.1016/j.semcancer.2015.09.007
    [Google Scholar]
  22. Wang Y. Li J. Xia L. Plant-derived natural products and combination therapy in liver cancer. Front. Oncol. 2023 13 1116532 10.3389/fonc.2023.1116532 36865794
    [Google Scholar]
  23. Abu-Izneid T. Rauf A. Khalil A.A. Olatunde A. Khalid A. Alhumaydhi F.A. Aljohani A.S.M. Sahab Uddin M. Heydari M. Khayrullin M. Shariati M.A. Aremu A.O. Alafnan A. Rengasamy K.R.R. Nutritional and health beneficial properties of saffron ( Crocus sativus L): a comprehensive review. Crit. Rev. Food Sci. Nutr. 2022 62 10 2683 2706 10.1080/10408398.2020.1857682 33327732
    [Google Scholar]
  24. Huang L. Han Y. Wang Z. Qiu Q. Yue S. Zhou Q. Su W. Yan J. Saffron reduces the liver fibrosis in mice by inhibiting the JAK/STAT3 pathway. Acta Cir. Bras. 2023 38 e385823 10.1590/acb385823 38055395
    [Google Scholar]
  25. Elfardi Y.R. El Boukhari R. Fatimi A. Bouissane L. The multifaceted therapeutic potential of saffron: an overview based on research and patents. Drugs and Drug Candidates 2024 3 3 437 454 10.3390/ddc3030026
    [Google Scholar]
  26. Boozari M. Hosseinzadeh H. Crocin molecular signaling pathways at a glance: A comprehensive review. Phytother. Res. 2022 36 10 3859 3884 10.1002/ptr.7583 35989419
    [Google Scholar]
  27. Rashidi K. Korani M. Nemati H. Shahraki R. Korani S. Abbasifard M. Majeed M. Jamialahmadi T. Sahebkar A. The combined effect of curcumin and crocin on the reduction of inflammatory responses in arthritic rats. Curr. Med. Chem. 2024 31 28 4562 4577 10.2174/0929867330666230409003744 37031388
    [Google Scholar]
  28. Veisi A. Akbari G. Role of crocin in several cancer cell lines: An updated review. Iran J Basic Med Sci. 2020 23 1 3 12
    [Google Scholar]
  29. Mishra Y. Mishra V. Multifaceted roles of crocin, phytoconstituent of Crocus sativus L. in cancer treatment: An expanding horizon. S. Afr. J. Bot. 2023 160 456 468 10.1016/j.sajb.2023.07.038
    [Google Scholar]
  30. Mollaei H. Safaralizadeh R. Babaei E. Abedini M.R. Hoshyar R. The anti-proliferative and apoptotic effects of crocin on chemosensitive and chemoresistant cervical cancer cells. Biomed. Pharmacother. 2017 94 307 316 10.1016/j.biopha.2017.07.052 28763753
    [Google Scholar]
  31. Jia Y. Yang H. Yu J. Li Z. Jia G. Ding B. Lv C. Crocin suppresses breast cancer cell proliferation by down‐regulating tumor promoter miR ‐122‐5p and up‐regulating tumor suppressors FOXP2 and SPRY2. Environ. Toxicol. 2023 38 7 1597 1608 10.1002/tox.23789 36988377
    [Google Scholar]
  32. Pourmousavi L. Asadi R.H. Zehsaz F. Jadidi R.P. Effect of crocin and treadmill exercise on oxidative stress and heart damage in diabetic rats bioRxiv 2023.02.01.526596 2023 10.1101/2023.02.01.526596
    [Google Scholar]
  33. Mohamadpour A.H. Ayati Z. Parizadeh M.R. Rajbai O. Hosseinzadeh H. Safety evaluation of crocin (a constituent of saffron) tablets in healthy volunteers. Iran. J. Basic Med. Sci. 2013 16 1 39 46 23638291
    [Google Scholar]
  34. Thuy N.M. Nhu P.H. Tai N.V. Minh V.Q. Extraction optimization of crocin from gardenia (Gardenia jasminoides ellis)fruits using response surface methodology and quality evaluation of foam-mat dried powder. Horticulturae 2022 8 12 1199 10.3390/horticulturae8121199
    [Google Scholar]
  35. Rahaiee S. Shojaosadati S.A. Hashemi M. Moini S. Razavi S.H. Improvement of crocin stability by biodegradeble nanoparticles of chitosan-alginate. Int. J. Biol. Macromol. 2015 79 423 432 10.1016/j.ijbiomac.2015.04.041 25934104
    [Google Scholar]
  36. Song Y. Wang Y. Zheng Y. Liu T. Zhang C. Crocins: A comprehensive review of structural characteristics, pharmacokinetics and therapeutic effects. Fitoterapia 2021 153 104969 10.1016/j.fitote.2021.104969 34147548
    [Google Scholar]
  37. Esposito E. Drechsler M. Mariani P. Panico A.M. Cardile V. Crascì L. Carducci F. Graziano A.C.E. Cortesi R. Puglia C. Nanostructured lipid dispersions for topical administration of crocin, a potent antioxidant from saffron (Crocus sativus L.). Mater. Sci. Eng. C 2017 71 669 677 10.1016/j.msec.2016.10.045 27987758
    [Google Scholar]
  38. Wang L. Cao Y. Zhang X. Liu C. Yin J. Kuang L. He W. Hua D. Reactive oxygen species-responsive nanodrug of natural crocin-i with prolonged circulation for effective radioprotection. Colloids Surf. B Biointerfaces 2022 213 112441 10.1016/j.colsurfb.2022.112441 35272253
    [Google Scholar]
  39. Dehelean C.A. Marcovici I. Soica C. Mioc M. Coricovac D. Iurciuc S. Cretu O.M. Pinzaru I. Plant-derived anticancer compounds as new perspectives in drug discovery and alternative therapy. Molecules 2021 26 4 1109 10.3390/molecules26041109 33669817
    [Google Scholar]
  40. Najmi A. Javed S.A. Al Bratty M. Alhazmi H.A. modern approaches in the discovery and development of plant-based natural products and their analogues as potential therapeutic agents. Molecules 2022 27 2 349 10.3390/molecules27020349 35056662
    [Google Scholar]
  41. Saravani R. Sargazi S. Saravani R. Rabbani M. Rahdar A. Taboada P. Newly crocin-coated magnetite nanoparticles induce apoptosis and decrease VEGF expression in breast carcinoma cells. J. Drug Deliv. Sci. Technol. 2020 60 101987 10.1016/j.jddst.2020.101987
    [Google Scholar]
  42. Tietze R. Zaloga J. Unterweger H. Lyer S. Friedrich R.P. Janko C. Pöttler M. Dürr S. Alexiou C. Magnetic nanoparticle-based drug delivery for cancer therapy. Biochem. Biophys. Res. Commun. 2015 468 3 463 470 10.1016/j.bbrc.2015.08.022 26271592
    [Google Scholar]
  43. Gavas S. Quazi S. Karpiński T.M. Nanoparticles for cancer therapy: current progress and challenges. Nanoscale Res. Lett. 2021 16 1 173 10.1186/s11671‑021‑03628‑6 34866166
    [Google Scholar]
  44. Kim D.G. Jung K.H. Lee D.G. Yoon J.H. Choi K.S. Kwon S.W. Shen H.M. Morgan M.J. Hong S.S. Kim Y.S. 20(S)-Ginsenoside Rg3 is a novel inhibitor of autophagy and sensitizes hepatocellular carcinoma to doxorubicin. Oncotarget 2014 5 12 4438 4451 10.18632/oncotarget.2034 24970805
    [Google Scholar]
  45. Izzularab B.M. Megeed M. Yehia M. Propolis nanoparticles modulate the inflammatory and apoptotic pathways in carbon tetrachloride‐induced liver fibrosis and nephropathy in rats. Environ. Toxicol. 2021 36 1 55 66 10.1002/tox.23010 32840962
    [Google Scholar]
  46. Li D. Wu G. Zhang H. Qi X. Preparation of crocin nanocomplex in order to increase its physical stability. Food Hydrocoll. 2021 120 106415 10.1016/j.foodhyd.2020.106415
    [Google Scholar]
  47. Zhang A. Shen Y. Cen M. Hong X. Shao Q. Chen Y. Zheng B. Polysaccharide and crocin contents, and antioxidant activity of saffron from different origins. Ind. Crops Prod. 2019 133 111 117 10.1016/j.indcrop.2019.03.009
    [Google Scholar]
  48. Chung D.M. Kim J.H. Kim J.K. Evaluation of MTT and Trypan Blue assays for radiation-induced cell viability test in HepG2 cells. Int J Radiat Res. 2015 13 4 331 335
    [Google Scholar]
  49. Pietkiewicz S. Schmidt J.H. Lavrik I.N. Quantification of apoptosis and necroptosis at the single cell level by a combination of Imaging Flow Cytometry with classical Annexin V/propidium iodide staining. J. Immunol. Methods 2015 423 99 103 10.1016/j.jim.2015.04.025 25975759
    [Google Scholar]
  50. Nunez R. DNA measurement and cell cycle analysis by flow cytometry. Curr. Issues Mol. Biol. 2001 3 3 67 70 11488413
    [Google Scholar]
  51. Livak K.J. Schmittgen T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Δ Δ C(T)) Method. Methods 2001 25 4 402 408 10.1006/meth.2001.1262 11846609
    [Google Scholar]
  52. Hakkim L. Molecular mechanism of crocin induced caspase mediated MCF-7 cell death: in vivo toxicity profiling and ex vivo macrophage activation. Asian Pac J Cancer Prev APJCP. 2016 17 1499 1506
    [Google Scholar]
  53. El-Kharrag R. Amin A. Hisaindee S. Greish Y. Karam S.M. Development of a therapeutic model of precancerous liver using crocin-coated magnetite nanoparticles. Int. J. Oncol. 2017 50 1 212 222 10.3892/ijo.2016.3769 27878253
    [Google Scholar]
  54. El-Sewedy T. Salama A.F. Mohamed A.E. Elbaioumy N.M. El-Far A.H. Albalawi A.N. Elmetwalli A. Hepatocellular Carcinoma cells: activity of Amygdalin and Sorafenib in Targeting AMPK /mTOR and BCL-2 for anti-angiogenesis and apoptosis cell death. BMC Complementary Medicine and Therapies 2023 23 1 329 10.1186/s12906‑023‑04142‑1 37726740
    [Google Scholar]
  55. Cutts S.M. Rephaeli A. Nudelman A. Hmelnitsky I. Phillips D.R. Molecular basis for the synergistic interaction of adriamycin with the formaldehyde-releasing prodrug pivaloyloxymethyl butyrate (AN-9). Cancer Res. 2001 61 22 8194 8202 11719450
    [Google Scholar]
  56. Yokochi T. Robertson K.D. Doxorubicin inhibits DNMT1, resulting in conditional apoptosis. Mol. Pharmacol. 2004 66 6 1415 1420 10.1124/mol.104.002634 15340041
    [Google Scholar]
  57. Saito G. Swanson J.A. Lee K.D. Drug delivery strategy utilizing conjugation via reversible disulfide linkages: role and site of cellular reducing activities. Adv. Drug Deliv. Rev. 2003 55 2 199 215 10.1016/S0169‑409X(02)00179‑5 12564977
    [Google Scholar]
  58. Milajerdi A. Djafarian K. Hosseini B. The toxicity of saffron (Crocus sativus L.) and its constituents against normal and cancer cells. J. Nutr. Intermed. Metab. 2016 3 23 32 10.1016/j.jnim.2015.12.332
    [Google Scholar]
  59. Fabiano A. De Leo M. Cerri L. Piras A.M. Braca A. Zambito Y. Saffron extract self-assembled nanoparticles to prolong the precorneal residence of crocin. J. Drug Deliv. Sci. Technol. 2022 74 103580 10.1016/j.jddst.2022.103580
    [Google Scholar]
  60. Bohrey S. Chourasiya V. Pandey A. Polymeric nanoparticles containing diazepam: preparation, optimization, characterization, in-vitro drug release and release kinetic study. Nano Converg. 2016 3 1 3 10.1186/s40580‑016‑0061‑2 28191413
    [Google Scholar]
  61. Gandhi A. Jana S. Sen K.K. In-vitro release of acyclovir loaded Eudragit RLPO® nanoparticles for sustained drug delivery. Int. J. Biol. Macromol. 2014 67 478 482 10.1016/j.ijbiomac.2014.04.019 24755259
    [Google Scholar]
  62. van Meerloo J. Kaspers G.J.L. Cloos J. Cell sensitivity assays: the MTT assay. Methods Mol. Biol. 2011 731 237 245 10.1007/978‑1‑61779‑080‑5_20 21516412
    [Google Scholar]
  63. Rahaiee S. Hashemi M. Shojaosadati S.A. Moini S. Razavi S.H. Nanoparticles based on crocin loaded chitosan-alginate biopolymers: Antioxidant activities, bioavailability and anticancer properties. Int. J. Biol. Macromol. 2017 99 401 408 10.1016/j.ijbiomac.2017.02.095 28254570
    [Google Scholar]
  64. Puglia C. Santonocito D. Musumeci T. Cardile V. Graziano A. Salerno L. Raciti G. Crascì L. Panico A. Puglisi G. Nanotechnological Approach to Increase the Antioxidant and Cytotoxic Efficacy of Crocin and Crocetin. Planta Med. 2019 85 3 258 265 10.1055/a‑0732‑5757 30206907
    [Google Scholar]
  65. Aung H.H. Wang C.Z. Ni M. Fishbein A. Mehendale S.R. Xie J.T. Shoyama C.Y. Yuan C.S. Crocin from Crocus sativus possesses significant anti-proliferation effects on human colorectal cancer cells. Exp. Oncol. 2007 29 3 175 180 18004240
    [Google Scholar]
  66. Guzmán M. Cannabinoids: potential anticancer agents. Nat. Rev. Cancer 2003 3 10 745 755 10.1038/nrc1188 14570037
    [Google Scholar]
  67. Zwaal R.F.A. Comfurius P. Bevers E.M. Surface exposure of phosphatidylserine in pathological cells. Cell. Mol. Life Sci. 2005 62 9 971 988 10.1007/s00018‑005‑4527‑3 15761668
    [Google Scholar]
  68. Kim J.A. Åberg C. Salvati A. Dawson K.A. Role of cell cycle on the cellular uptake and dilution of nanoparticles in a cell population. Nat. Nanotechnol. 2012 7 1 62 68 10.1038/nnano.2011.191 22056728
    [Google Scholar]
  69. Amin A. Hamza A.A. Daoud S. Khazanehdari K. Hrout A.A. Baig B. Chaiboonchoe A. Adrian T.E. Zaki N. Salehi-Ashtiani K. Saffron-Based Crocin Prevents Early Lesions of Liver Cancer: In vivo, In vitro and Network Analyses. Recent Patents Anticancer Drug Discov. 2016 11 1 121 133 10.2174/1574892810666151102110248 26522014
    [Google Scholar]
  70. Chen F. Chang D. Goh M. Klibanov S.A. Ljungman M. Role of p53 in cell cycle regulation and apoptosis following exposure to proteasome inhibitors. Cell Growth Differ. 2000 11 5 239 246 10845424
    [Google Scholar]
  71. Tsapras P. Nezis I.P. Caspase involvement in autophagy. Cell Death Differ. 2017 24 8 1369 1379 10.1038/cdd.2017.43 28574508
    [Google Scholar]
  72. Lockshin R.A. Zakeri Z. Apoptosis, autophagy, and more. Int. J. Biochem. Cell Biol. 2004 36 12 2405 2419 10.1016/j.biocel.2004.04.011 15325581
    [Google Scholar]
  73. Amin A. Bajbouj K. Koch A. Gandesiri M. Schneider-Stock R. Defective autophagosome formation in p53-null colorectal cancer reinforces crocin-induced apoptosis. Int. J. Mol. Sci. 2015 16 1 1544 1561 10.3390/ijms16011544 25584615
    [Google Scholar]
  74. Bakshi H. Zoubi M. Faruck H. Aljabali A. Rabi F. Hafiz A. Al-Batanyeh K. Al-Trad B. Ansari P. Nasef M. Charbe N. Satija S. Mehta M. Mishra V. Gupta G. Abobaker S. Negi P. Azzouz I. Dardouri A. Dureja H. Prasher P. Chellappan D. Dua K. Webba da Silva M. Tanani M. McCarron P. Tambuwala M. Dietary Crocin is Protective in Pancreatic Cancer while Reducing Radiation-Induced Hepatic Oxidative Damage. Nutrients 2020 12 6 1901 10.3390/nu12061901 32604971
    [Google Scholar]
  75. Ye X. Zhou X.J. Zhang H. Exploring the Role of Autophagy-Related Gene 5 (ATG5) Yields Important Insights Into Autophagy in Autoimmune/Autoinflammatory Diseases. Front. Immunol. 2018 9 2334 10.3389/fimmu.2018.02334 30386331
    [Google Scholar]
  76. Lee Y.K. Lee J.A. Role of the mammalian ATG8/LC3 family in autophagy: differential and compensatory roles in the spatiotemporal regulation of autophagy. BMB Rep. 2016 49 8 424 430 10.5483/BMBRep.2016.49.8.081 27418283
    [Google Scholar]
  77. Yao C. Liu B.B. Qian X.D. Li L.Q. Cao H.B. Guo Q.S. Zhou G.F. Crocin induces autophagic apoptosis in hepatocellular carcinoma by inhibiting Akt/mTOR activity. OncoTargets Ther. 2018 11 2017 2028 10.2147/OTT.S154586 29670377
    [Google Scholar]
/content/journals/acamc/10.2174/0118715206327654240823074318
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Therapeutic Effects of Crocin Nanoparticles Alone or in Combination with Doxorubicin against Hepatocellular Carcinoma In vitro
Bentham Science Publishers ; https://doi.org/10.2174/0118715206327654240823074318
/content/journals/acamc/10.2174/0118715206327654240823074318
/content/journals/acamc/10.2174/0118715206327654240823074318
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  • Article Type:     Research Article
Keywords: Hepatocellular carcinoma ; crocin nanoparticles ; crocin ; apoptosis ; autophagy ; doxorubicin

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