Induction of immunogenic cell death and enhancement of the radiation-induced immunogenicity by chrysin in melanoma cancer cells.
Flavonoids
/ pharmacology
Animals
Immunogenic Cell Death
/ drug effects
Mice
Cell Line, Tumor
Calreticulin
/ metabolism
Melanoma, Experimental
/ immunology
Apoptosis
/ drug effects
HMGB1 Protein
/ metabolism
STAT3 Transcription Factor
/ metabolism
Cell Survival
/ drug effects
Dendritic Cells
/ immunology
B7-H1 Antigen
/ metabolism
Interleukin-12
/ metabolism
HSP70 Heat-Shock Proteins
/ metabolism
Adenosine Triphosphate
/ metabolism
AMPs
B16-F10 cells
Chrysin
IL-12
PDL-1
Radiation
STAT3
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
05 Oct 2024
05 Oct 2024
Historique:
received:
08
11
2023
accepted:
10
09
2024
medline:
6
10
2024
pubmed:
6
10
2024
entrez:
5
10
2024
Statut:
epublish
Résumé
Chrysin is a natural flavonoid with anti-cancer effects. Despite its beneficial effects, little information is available regarding its immunogenic cell death (ICD) properties. In this work, we hypothesized that chrysin can potentiate radiotherapy(RT)-induced immunogenicity in melanoma cell line (B16-F10). We examined the effects of chrysin alone and in combination with radiation on ICD induction in B16-F10 cells. Cell viability was assessed using an MTT assay. Cell apoptosis and calreticulin (CRT) exposure were determined using flow cytometry. Western blotting and ELISA assay were employed to examine changes in protein expression. Combination therapy exhibited a synergistic effect, with an optimum combination index of 0.66. The synergistic anti-cancer effect correlated with increased cell apoptosis in cancer cells. Compared to the untreated control, chrysin alone and in combination with RT induced higher levels of DAMPs, such as CRT, HSP70, HMGB1, and ATP. The protein expression of p-STAT3/STAT3 and PD-L1 was reduced in B16-F10 cells exposed to chrysin alone and in combination with RT. Conditioned media from B16-F10 cells exposed to mono-and combination treatments elicited IL-12 secretion in dendritic cells (DCs), inducing a Th1 response. Our findings revealed that chrysin could induce ICD and intensify the RT-induced immunogenicity.
Identifiants
pubmed: 39369019
doi: 10.1038/s41598-024-72697-1
pii: 10.1038/s41598-024-72697-1
doi:
Substances chimiques
chrysin
3CN01F5ZJ5
Flavonoids
0
Calreticulin
0
HMGB1 Protein
0
STAT3 Transcription Factor
0
B7-H1 Antigen
0
Interleukin-12
187348-17-0
HSP70 Heat-Shock Proteins
0
Cd274 protein, mouse
0
Adenosine Triphosphate
8L70Q75FXE
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
23231Informations de copyright
© 2024. The Author(s).
Références
Sambi, M., Bagheri, L. & Szewczuk, M. R. Current challenges in cancer immunotherapy: Multimodal approaches to improve efficacy and patient response rates. J. Oncol. 2019 (2019).
Tesniere, A. et al. Molecular characteristics of immunogenic cancer cell death. Cell. Death Differ. 15, 3–12 (2008).
pubmed: 18007663
doi: 10.1038/sj.cdd.4402269
Ahmed, A. & Tait, S. W. Targeting immunogenic cell death in cancer. Mol. Oncol. 14, 2994–3006 (2020).
pubmed: 33179413
pmcid: 7718954
doi: 10.1002/1878-0261.12851
Garg, A. D. et al. Molecular and translational classifications of DAMPs in immunogenic cell DEATH. Front. Immunol. 6, 588 (2015).
pubmed: 26635802
pmcid: 4653610
doi: 10.3389/fimmu.2015.00588
Fucikova, J., Spisek, R., Kroemer, G. & Galluzzi, L. Calreticulin and cancer. Cell Res. 31, 5–16 (2021).
pubmed: 32733014
doi: 10.1038/s41422-020-0383-9
Dudek, A. M., Garg, A. D., Krysko, D. V., De Ruysscher, D. & Agostinis, P. Inducers of immunogenic cancer cell death. Cytokine Growth Factor Rev. 24, 319–333 (2013).
pubmed: 23391812
doi: 10.1016/j.cytogfr.2013.01.005
Hayashi, K. et al. Tipping the immunostimulatory and inhibitory DAMP balance to harness immunogenic cell death. Nat. Commun. 11, 6299 (2020).
pubmed: 33288764
pmcid: 7721802
doi: 10.1038/s41467-020-19970-9
Jafari, S., Heydarian, S., Lai, R., Aghdam, E. M. & Molavi, O. Silibinin induces immunogenic cell death in cancer cells and enhances the induced immunogenicity by chemotherapy. BIOIMPACTS (2022).
Jafari, S. et al. Clinical application of immune checkpoints in targeted immunotherapy of prostate cancer. Cell. Mol. Life Sci. 77, 3693–3710 (2020).
pubmed: 32006051
pmcid: 11104895
doi: 10.1007/s00018-020-03459-1
Wang, J., Wang, H. & Qian, H. -l. Biological effects of radiation on cancer cells. Military Med. Res. 5, 1–10 (2018).
doi: 10.1186/s40779-018-0167-4
Herrera, F. G., Bourhis, J. & Coukos, G. Radiotherapy combination opportunities leveraging immunity for the next oncology practice. Cancer J. Clin. 67, 65–85 (2017).
doi: 10.3322/caac.21358
Amiri, M., Molavi, O., Sabetkam, S., Jafari, S. & Montazersaheb, S. Stimulators of immunogenic cell death for cancer therapy: Focusing on natural compounds. Cancer Cell Int. 23, 200 (2023).
pubmed: 37705051
pmcid: 10500939
doi: 10.1186/s12935-023-03058-7
Moghadam, E. R. et al. Broad-spectrum preclinical antitumor activity of chrysin: Current trends and future perspectives. Biomolecules. 10, 1374 (2020).
pubmed: 32992587
pmcid: 7600196
doi: 10.3390/biom10101374
Dabiri, S., Jafari, S. & Molavi, O. Advances in nanocarrier-mediated delivery of chrysin: Enhancing solubility, bioavailability, and anticancer efficacy. BioImpacts, - (2024).
Talebi, M. et al. Emerging cellular and molecular mechanisms underlying anticancer indications of chrysin. Cancer Cell Int. 21, 1–20 (2021).
doi: 10.1186/s12935-021-01906-y
Jafari, S. et al. Synergistic effect of chrysin and radiotherapy against triple-negative breast cancer (TNBC) cell lines. Clin. Transl. Oncol. 25, 2559–2568 (2023).
pubmed: 36964888
doi: 10.1007/s12094-023-03141-5
Zou, S. et al. Targeting STAT3 in cancer immunotherapy. Mol. Cancer. 19, 1–19 (2020).
doi: 10.1186/s12943-020-01258-7
Sun, C., Mezzadra, R. & Schumacher, T. N. Regulation and function of the PD-L1 checkpoint. Immunity. 48, 434–452 (2018).
pubmed: 29562194
pmcid: 7116507
doi: 10.1016/j.immuni.2018.03.014
Wang, X. et al. Tumor cell-intrinsic PD-1 receptor is a tumor suppressor and mediates resistance to PD-1 blockade therapy. Proc. Natl. Acad. Sci. 117, 6640–6650 (2020).
Galvao, J. et al. Unexpected low-dose toxicity of the universal solvent DMSO. FASEB J. 28, 1317–1330 (2014).
pubmed: 24327606
doi: 10.1096/fj.13-235440
Pichichero, E., Cicconi, R., Mattei, M., Muzi, M. G. & Canini, A. Acacia honey and chrysin reduce proliferation of melanoma cells through alterations in cell cycle progression. Int. J. Oncol. 37, 973–981 (2010).
pubmed: 20811719
Xue, C. et al. Chrysin induces cell apoptosis in human uveal melanoma cells via intrinsic apoptosis. Oncol. Lett. 12, 4813–4820 (2016).
pubmed: 28105189
pmcid: 5228444
doi: 10.3892/ol.2016.5251
Molavi, O., Torkzaban, F., Jafari, S., Asnaashari, S. & Asgharian, P. Chemical compositions and anti-proliferative activity of the aerial parts and rhizomes of squirting cucumber, Cucurbitaceae. Jundishapur J. Nat. Pharm. Prod. 15 (2020).
Zoi, V. et al. Curcumin and radiotherapy exert synergistic anti-glioma effect in vitro. Biomedicines. 9, 1562 (2021).
pubmed: 34829791
pmcid: 8615260
doi: 10.3390/biomedicines9111562
Chendil, D., Ranga, R. S., Meigooni, D., Sathishkumar, S. & Ahmed, M. M. Curcumin confers radiosensitizing effect in prostate cancer cell line PC-3. Oncogene. 23, 1599–1607 (2004).
pubmed: 14985701
doi: 10.1038/sj.onc.1207284
Montazersaheb, S. et al. The synergistic effects of betanin and radiotherapy in a prostate cancer cell line: An in vitro study. Mol. Biol. Rep. 50, 9307–9314 (2023).
pubmed: 37812356
doi: 10.1007/s11033-023-08828-0
Farjami, A., Siahi-Shadbad, M., Akbarzadehlaleh, P., Roshanzamir, K. & Molavi, O. Evaluation of the physicochemical and biological stability of cetuximab under various stress condition. J. Pharm. Pharm. Sci. 22, 171–190 (2019).
pubmed: 31112673
doi: 10.18433/jpps30427
Montazersaheb, S. et al. Targeting TdT gene expression in Molt-4 cells by PNA-octaarginine conjugates. Int. J. Biol. Macromol. 164, 4583–4590 (2020).
pubmed: 32941907
doi: 10.1016/j.ijbiomac.2020.09.081
Rahimi, M. et al. Renoprotective effects of prazosin on ischemia-reperfusion injury in rats. Hum. Exp. Toxicol. 40, 1263–1273 (2021).
pubmed: 33559503
doi: 10.1177/0960327121993224
Farahzadi, R., Fathi, E., Mesbah-Namin, S. A. & Vietor, I. Granulocyte differentiation of rat bone marrow resident C-kit + hematopoietic stem cells induced by mesenchymal stem cells could be considered as new option in cell-based therapy. Regener. Ther.. 23, 94–101 (2023).
doi: 10.1016/j.reth.2023.04.004
Heidari, H. R. et al. Mesenchymal stem cells cause telomere length reduction of molt-4 cells via caspase-3, BAD and P53 apoptotic pathway. Int. J. Mol. Cell. Med. 10, 113 (2021).
pubmed: 34703795
pmcid: 8496249
Fathi, E., Azarbad, S., Farahzadi, R., Javanmardi, S. & Vietor, I. Effect of rat bone marrow derived-mesenchymal stem cells on granulocyte differentiation of mononuclear cells as preclinical agent in cellbased therapy. Curr. Gene Ther. 22, 152–161 (2022).
pubmed: 34011256
doi: 10.2174/1566523221666210519111933
Xu, H. et al. Deguelin induces the apoptosis of lung cancer cells through regulating a ROS driven Akt pathway. Cancer Cell Int. 15, 1–9 (2015).
doi: 10.1186/s12935-015-0166-4
Garg, S. M., Vakili, M. R., Molavi, O. & Lavasanifar, A. Self-associating poly (ethylene oxide)-block-poly (α-carboxyl-ε-caprolactone) drug conjugates for the delivery of STAT3 inhibitor JSI-124: Potential application in cancer immunotherapy. Mol. Pharm. 14, 2570–2584 (2017).
pubmed: 28221800
doi: 10.1021/acs.molpharmaceut.6b01119
Jafari, S. et al. STAT3 inhibitory stattic enhances immunogenic cell death induced by chemotherapy in cancer cells. DARU J. Pharm. Sci. 28, 159–169 (2020).
doi: 10.1007/s40199-020-00326-z
Circu, M. L. & Aw, T. Y. Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic. Biol. Med. 48, 749–762 (2010).
pubmed: 20045723
pmcid: 2823977
doi: 10.1016/j.freeradbiomed.2009.12.022
Wojno, E. D. T., Hunter, C. A. & Stumhofer, J. S. The immunobiology of the interleukin-12 family: Room for discovery. Immunity. 50, 851–870 (2019).
pmcid: 6472917
doi: 10.1016/j.immuni.2019.03.011
Showalter, A. et al. Cytokines in immunogenic cell death: Applications for cancer immunotherapy. Cytokine. 97, 123–132 (2017).
pubmed: 28648866
pmcid: 5572581
doi: 10.1016/j.cyto.2017.05.024
Welsh, J. et al. Abscopal effect following radiation therapy in cancer patients: A new look from the immunological point of view. J. Biomedical Phys. Eng. 10, 537 (2020).
Sharabi, A. B., Lim, M., DeWeese, T. L. & Drake, C. G. Radiation and checkpoint blockade immunotherapy: Radiosensitisation and potential mechanisms of synergy. Lancet Oncol. 16, e498–e509 (2015).
pubmed: 26433823
doi: 10.1016/S1470-2045(15)00007-8
Oliyapour, Y. et al. Chrysin and chrysin-loaded nanocarriers induced immunogenic cell death on B16 melanoma cells. Med. Oncol. 40, 278 (2023).
pubmed: 37624439
doi: 10.1007/s12032-023-02145-z
Mani, R., Natesan, V. & Chrysin sources, beneficial pharmacological activities, and molecular mechanism of action. Phytochemistry. 145, 187–196 (2018).
pubmed: 29161583
doi: 10.1016/j.phytochem.2017.09.016
Kasala, E. R., Bodduluru, L. N., Barua, C. C. & Gogoi, R. Chrysin and its emerging role in cancer drug resistance. Chemico-Biol. Interact. 236, 7–8 (2015).
doi: 10.1016/j.cbi.2015.04.017
Fucikova, J. et al. Detection of immunogenic cell death and its relevance for cancer therapy. Cell Death Dis. 11, 1–13 (2020).
doi: 10.1038/s41419-020-03221-2
Okada, K. et al. Calreticulin Upregulation in Cervical cancer Tissues from Patients Following 10 gy Radiotherapy. Adv. Radiation Oncol., 101159 (2022).
Huang, Y., Kong, L. & Lu, J. Ecto-calreticulin expression after particle irradiation versus conventional photon irradiation in human cancer cell lines. Int. J. Radiat. Oncol. Biol. Phys. 105, E643 (2019).
doi: 10.1016/j.ijrobp.2019.06.1109
Okada, K. et al. Calreticulin Upregulation in cervical cancer tissues from patients after 10 gy radiation therapy. Adv. Radiation Oncol. 8, 101159 (2023).
doi: 10.1016/j.adro.2022.101159
Tang, D. et al. High-mobility Group box 1 is essential for mitochondrial quality control. Cell Metabol. 13, 701–711 (2011).
doi: 10.1016/j.cmet.2011.04.008
Zhou, J. et al. Immunogenic cell death in cancer therapy: present and emerging inducers. J. Cell. Mol. Med. 23, 4854–4865 (2019).
pubmed: 31210425
pmcid: 6653385
doi: 10.1111/jcmm.14356
Ashrafizadeh, M., Farhood, B., Musa, A. E., Taeb, S. & Najafi, M. Damage-associated molecular patterns in tumor radiotherapy. Int. Immunopharmacol. 86, 106761 (2020).
pubmed: 32629409
doi: 10.1016/j.intimp.2020.106761
Zhu, M. et al. Immunogenic cell death induction by ionizing radiation. Front. Immunol. 12, 705361 (2021).
pubmed: 34489957
pmcid: 8417736
doi: 10.3389/fimmu.2021.705361
Vaes, R. D., Hendriks, L. E., Vooijs, M. & De Ruysscher, D. Biomarkers of radiotherapy-induced immunogenic cell death. Cells. 10, 930 (2021).
pubmed: 33920544
pmcid: 8073519
doi: 10.3390/cells10040930
Wang, X. et al. Targeting STAT3 enhances ndv-induced immunogenic cell death in prostate cancer cells. J. Cell. Mol. Med. 24, 4286–4297 (2020).
pubmed: 32100392
pmcid: 7171322
doi: 10.1111/jcmm.15089
Bu, L. et al. STAT3 induces immunosuppression by upregulating PD-1/PD-L1 in HNSCC. J. Dent. Res. 96, 1027–1034 (2017).
pubmed: 28605599
pmcid: 6728673
doi: 10.1177/0022034517712435
Yu, H., Kortylewski, M. & Pardoll, D. Crosstalk between cancer and immune cells: Role of STAT3 in the tumour microenvironment. Nat. Rev. Immunol. 7, 41–51 (2007).
pubmed: 17186030
doi: 10.1038/nri1995
Wang, Y., Shen, Y., Wang, S., Shen, Q. & Zhou, X. The role of STAT3 in leading the crosstalk between human cancers and the immune system. Cancer Lett. 415, 117–128 (2018).
pubmed: 29222039
doi: 10.1016/j.canlet.2017.12.003
Rébé, C. & Ghiringhelli, F. STAT3, a master regulator of anti-tumor immune response. Cancers. 11, 1280 (2019).
pubmed: 31480382
pmcid: 6770459
doi: 10.3390/cancers11091280
Zerdes, I. et al. STAT3 activity promotes programmed-death ligand 1 expression and suppresses immune responses in breast cancer. Cancers. 11, 1479 (2019).
pubmed: 31581535
pmcid: 6827034
doi: 10.3390/cancers11101479
Sato, H., Okonogi, N. & Nakano, T. Rationale of combination of anti-PD-1/PD-L1 antibody therapy and radiotherapy for cancer treatment. Int. J. Clin. Oncol. 25, 801–809 (2020).
pubmed: 32246277
pmcid: 7192886
doi: 10.1007/s10147-020-01666-1
Tesniere, A. et al. Immunogenic death of colon cancer cells treated with oxaliplatin. Oncogene. 29, 482–491 (2010).
pubmed: 19881547
doi: 10.1038/onc.2009.356
Fang, H. et al. TLR4 is essential for dendritic cell activation and anti-tumor t-cell response enhancement by DAMPs released from chemically stressed cancer cells. Cell Mol. Immunol. 11, 150–159 (2014).
pubmed: 24362470
doi: 10.1038/cmi.2013.59