Curcumin Suppresses M2 Macrophage-derived Paclitaxel Chemoresistance through Inhibition of PI3K-AKT/STAT3 Signaling


Cite item

Full Text

Abstract

Background:Breast cancer is the leading cancer in women worldwide. The development of chemoresistance that leads to recurrence and mortality remains a major concern. M2-type tumor-associated macrophages (TAMs), present in the breast tumor microenvironment, secrete various cytokines and growth factors that induce chemoresistance. Curcumin, isolated from Curcuma longa, is known to sensitize cancer cells and increase the efficacy of standard chemotherapeutic agents. However, the effect of curcumin on the chemoresistancegenerating ability of M2 TAMs is not known.

Objective:The study aimed to determine whether curcumin could modulate M2 macrophages and suppress their ability to induce resistance to paclitaxel in breast cancer cells.

Methods:THP-1 cells were differentiated to M2 macrophages using PMA and IL-4/IL-13 in the presence or absence of curcumin in vitro. The effect of the conditioned medium of M2 macrophages on inducing resistance towards paclitaxel in MCF-7 or MDA-MB-231 cells was analyzed by cell proliferation assay, cell cycle analysis, wound healing and transwell migration assays. RT-PCR analysis was used to determine the mRNA expression of anti-inflammatory cytokines in M2 macrophages. The effect of curcumin on TGF-β, pAKT, and pSTAT3 in M2 macrophages was analyzed by western blotting.

Results:Our data revealed that the M2 macrophages polarized in the presence of curcumin lacked the ability to generate chemoresistance to paclitaxel in breast cancer cell lines. Transcriptomic analysis revealed the expression of TGF-β to be highest amongst M2 macrophage-secreted cytokines. We observed that purified recombinant TGF-β generated chemoresistance in breast cancer cells. We found that curcumin treatment abrogated the expression of TGF-β in M2 macrophages and suppressed their ability to induce chemoresistance in breast cancer cells. STITCH analysis showed strong interaction between curcumin and AKT/STAT3 pathway. Mechanistically, curcumin inhibited PI3K/AKT/STAT3 signaling in M2 macrophages. Western blot analysis revealed that M2 TAM CM, but not curcumin-treated macrophage CM, activated COX2/NF-κB in breast cancer cells.

Conclusion:Our results showed that curcumin reduced the chemoresistance-generating ability of M2 TAMs. The study has revealed a non-cancer cell-autonomous mechanism by which curcumin partly overcomes the chemoresistance of paclitaxel in breast cancer.

About the authors

Bhawna Deswal

Amity Institute of Molecular Medicine and Stem Cell Research (AIMMSCR), Amity University

Email: info@benthamscience.net

Urmi Bagchi

Amity Institute of Molecular Medicine and Stem Cell Research (AIMMSCR), Amity University

Email: info@benthamscience.net

Sonia Kapoor

Amity Institute of Molecular Medicine and Stem Cell Research (AIMMSCR), Amity University

Author for correspondence.
Email: info@benthamscience.net

References

  1. Jagetia, G.C.; Aggarwal, B.B. "Spicing up" of the immune system by curcumin. J. Clin. Immunol., 2007, 27(1), 19-35. doi: 10.1007/s10875-006-9066-7 PMID: 17211725
  2. Jiang, H.; Wei, H.; Wang, H. Zeb1-induced metabolic reprogramming of glycolysis is essential for macrophage polarization in breast cancer. Cell Death Dis., 2022, 13(3), 206. doi: 10.1038/s41419-022-04632-z
  3. Mentoor, I.; Engelbrecht, A.M.; van Jaarsveld, P.J.; Nell, T. Chemoresistance: Intricate interplay between breast tumor cells and adipocytes in the tumor microenvironment. Front. Endocrinol., 2018, 9, 758. doi: 10.3389/fendo.2018.00758
  4. Sica, A.; Mantovani, A. Macrophage plasticity and polarization: in vivo veritas. J. Clin. Invest., 2012, 122(3), 787-795. doi: 10.1172/JCI59643 PMID: 22378047
  5. Cassetta, L.; Pollard, J.W. Tumor-associated macrophages. Curr. Biol., 2020, 30(6), R246-R248. doi: 10.1016/j.cub.2020.01.031 PMID: 32208142
  6. Biswas, S.K.; Mantovani, A. Macrophage plasticity and interaction with lymphocyte subsets: Cancer as a paradigm. Nat. Immunol., 2010, 11(10), 889-896. doi: 10.1038/ni.1937 PMID: 20856220
  7. Nelson, K.M.; Dahlin, J.L.; Bisson, J.; Graham, J.; Pauli, G.F.; Walters, M.A. The essential medicinal chemistry of curcumin. J. Med. Chem., 2017, 60(5), 1620-1637. doi: 10.1021/acs.jmedchem.6b00975 PMID: 28074653
  8. Peng, Y.; Ao, M.; Dong, B. Anti-inflammatory effects of curcumin in the inflammatory diseases: Status, limitations and countermeasures. Drug Des. Devel. Ther., 2021, 15, 4503-4525. doi: 10.2147/DDDT.S327378
  9. Pricci, M.; Girardi, B.; Giorgio, F.; Losurdo, G.; Ierardi, E.; Di Leo, A. Curcumin and colorectal cancer: From basic to clinical evidences. Int. J. Mol. Sci., 2020, 21(7), 2364. doi: 10.3390/ijms21072364 PMID: 32235371
  10. Wang, L.; Wang, C.; Tao, Z.; Zhao, L.; Zhu, Z.; Wu, W.; He, Y.; Chen, H.; Zheng, B.; Huang, X.; Yu, Y.; Yang, L.; Liang, G.; Cui, R.; Chen, T. Curcumin derivative WZ35 inhibits tumor cell growth via ROS-YAP-JNK signaling pathway in breast cancer. J. Exp. Clin. Cancer Res., 2019, 38(1), 460. doi: 10.1186/s13046-019-1424-4 PMID: 31703744
  11. Ohnishi, Y.; Sakamoto, T.; Zhengguang, L.; Yasui, H.; Hamada, H.; Kubo, H.; Nakajima, M. Curcumin inhibits epithelial mesenchymal transition in oral cancer cells via c Met blockade. Oncol. Lett., 2020, 19(6), 4177-4182. doi: 10.3892/ol.2020.11523 PMID: 32391111
  12. Ghasemi, F.; Shafiee, M.; Banikazemi, Z.; Pourhanifeh, M.H.; Khanbabaei, H.; Shamshirian, A.; Moghadam, S. Curcumin inhibits NF-kB and Wnt/β-catenin pathways in cervical cancer cells. Pathol. Res. Pract., 2019, 215(10), 152556. doi: 10.1016/j.prp.2019.152556
  13. Tang, X.; Ding, H.; Liang, M.; Chen, X.; Yan, Y.; Wan, N.; Chen, Q.; Zhang, J.; Cao, J. Curcumin induces ferroptosis in non‐small‐cell lung cancer via activating autophagy. Thorac. Cancer, 2021, 12(8), 1219-1230. doi: 10.1111/1759-7714.13904 PMID: 33656766
  14. Kotha, R.R.; Luthria, D.L. Curcumin: Biological, pharmaceutical, nutraceutical, and analytical aspects. Molecules, 2019, 24(16), 2930. doi: 10.3390/molecules24162930 PMID: 31412624
  15. Giordano, A.; Tommonaro, G. Curcumin and cancer. Nutrients, 2019, 11(10), 2376. doi: 10.3390/nu11102376 PMID: 31590362
  16. Chu, Y.W.; Liu, S.T.; Cheng, H.C.; Huang, S.M.; Chang, Y.L.; Chiang, C.P.; Liu, Y.C.; Wang, W.M. Opposing effects of zac1 and curcumin on AP-1-Regulated expressions of S100A7. PLoS One, 2015, 10(12), e0144175. doi: 10.1371/journal.pone.0144175 PMID: 26633653
  17. Nakamae, I.; Morimoto, T.; Shima, H.; Shionyu, M.; Fujiki, H.; Yoneda-Kato, N.; Yokoyama, T.; Kanaya, S.; Kakiuchi, K.; Shirai, T.; Meiyanto, E.; Kato, J. Curcumin derivatives verify the essentiality of ros upregulation in tumor suppression. Molecules, 2019, 24(22), 4067. doi: 10.3390/molecules24224067 PMID: 31717651
  18. Cheng, C.; Jiao, J.T.; Qian, Y.; Guo, X.Y.; Huang, J.; Dai, M.C.; Zhang, L.; Ding, X.P.; Zong, D.; Shao, J.F. Curcumin induces G2/M arrest and triggers apoptosis via FoxO1 signaling in U87 human glioma cells. Mol. Med. Rep., 2016, 13(5), 3763-3770. doi: 10.3892/mmr.2016.5037 PMID: 27035875
  19. Khan, A.Q.; Ahmed, E.I.; Elareer, N.; Fathima, H.; Prabhu, K.S.; Siveen, K.S.; Kulinski, M.; Azizi, F.; Dermime, S.; Ahmad, A.; Steinhoff, M.; Uddin, S. Curcumin-mediated apoptotic cell death in papillary thyroid cancer and cancer stem-like cells through targeting of the JAK/STAT3 signaling pathway. Int. J. Mol. Sci., 2020, 21(2), 438. doi: 10.3390/ijms21020438 PMID: 31936675
  20. Senthebane, D.A.; Rowe, A.; Thomford, N.E.; Shipanga, H.; Munro, D.; Mazeedi, M.A.M.A.; Almazyadi, H.A.M.; Kallmeyer, K.; Dandara, C.; Pepper, M.S.; Parker, M.I.; Dzobo, K. The role of tumor microenvironment in chemoresistance: To survive, keep your enemies closer. Int. J. Mol. Sci., 2017, 18(7), 1586. doi: 10.3390/ijms18071586 PMID: 28754000
  21. Farghadani, R.; Naidu, R. Curcumin as an enhancer of therapeutic efficiency of chemotherapy drugs in breast cancer. Int. J. Mol. Sci., 2022, 23(4), 2144. doi: 10.3390/ijms23042144 PMID: 35216255
  22. Ham, I.H.; Wang, L.; Lee, D.; Woo, J.; Kim, T.; Jeong, H.; Oh, H.; Choi, K.; Kim, T.M.; Hur, H. Curcumin inhibits the cancer associated fibroblast derived chemoresistance of gastric cancer through the suppression of the JAK/STAT3 signaling pathway. Int. J. Oncol., 2022, 61(1), 85. doi: 10.3892/ijo.2022.5375 PMID: 35621145
  23. Mukherjee, S.; Hussaini, R.; White, R.; Atwi, D.; Fried, A.; Sampat, S.; Piao, L.; Pan, Q.; Banerjee, P. TriCurin, a synergistic formulation of curcumin, resveratrol, and epicatechin gallate, repolarizes tumor-associated macrophages and triggers an immune response to cause suppression of HPV+ tumors. Cancer Immunol. Immunother., 2018, 67(5), 761-774. doi: 10.1007/s00262-018-2130-3 PMID: 29453519
  24. Gao, J.; Liang, Y.; Wang, L. Shaping polarization of tumor-associated macrophages in cancer immunotherapy. Front. Immunol., 2022, 13, 888713. doi: 10.3389/fimmu.2022.888713 PMID: 35844605
  25. Soni, V.K.; Mehta, A.; Ratre, Y.K. Counteracting action of curcumin on high glucose-induced chemoresistance in hepatic carcinoma cells. Front. Oncol., 2021, 11, 738961. doi: 10.3389/fonc.2021.738961
  26. Wu, M.F.; Huang, Y.H.; Chiu, L.Y.; Cherng, S.H.; Sheu, G.T.; Yang, T.Y. Curcumin induces apoptosis of chemoresistant lung cancer cells via ROS-Regulated p38 MAPK phosphorylation. Int. J. Mol. Sci., 2022, 23(15), 8248. doi: 10.3390/ijms23158248
  27. Sung, B.; Kunnumakkara, A.B.; Sethi, G.; Anand, P.; Guha, S.; Aggarwal, B.B. Curcumin circumvents chemoresistance in vitro and potentiates the effect of thalidomide and bortezomib against human multiple myeloma in nude mice model. Mol. Cancer Ther., 2009, 8(4), 959-970. doi: 10.1158/1535-7163.MCT-08-0905 PMID: 19372569
  28. Paciello, F.; Fetoni, A.R.; Mezzogori, D. The dual role of curcumin and ferulic acid in counteracting chemoresistance and cisplatin-induced ototoxicity. Sci. Rep., 2020, 10(1), 1063. doi: 10.1038/s41598-020-57965-0
  29. Tian, N.; Shangguan, W.; Zhou, Z.; Yao, Y.; Fan, C.; Cai, L. Lin28b is involved in curcumin-reversed paclitaxel chemoresistance and associated with poor prognosis in hepatocellular carcinoma. J. Cancer, 2019, 10(24), 6074-6087. doi: 10.7150/jca.33421
  30. Farghadani, R.; Naidu, R. Curcumin as an enhancer of therapeutic efficiency of chemotherapy drugs in breast cancer. Int. J. Mol. Sci., 2022, 23(4), 2144. doi: 10.3390/ijms23042144
  31. Kapoor, S.; Srivastava, S.; Panda, D. Indibulin dampens microtubule dynamics and produces synergistic antiproliferative effect with vinblastine in MCF-7 cells: Implications in cancer chemotherapy. Sci. Rep., 2018, 8(1), 12363. doi: 10.1038/s41598-018-30376-y PMID: 30120268
  32. Rai, A.; Kapoor, S.; Naaz, A.; Kumar, S.M.; Panda, D. Enhanced stability of microtubules contributes in the development of colchicine resistance in MCF-7 cells. Biochem. Pharmacol., 2017, 132, 38-47. doi: 10.1016/j.bcp.2017.02.018 PMID: 28242250
  33. Kapoor, S.; Panda, D. Kinetic stabilization of microtubule dynamics by indanocine perturbs EB1 localization, induces defects in cell polarity and inhibits migration of MDA-MB-231 cells. Biochem. Pharmacol., 2012, 83(11), 1495-1506. doi: 10.1016/j.bcp.2012.02.012 PMID: 22387536
  34. Rai, A.; Kapoor, S.; Singh, S.; Chatterji, B.P.; Panda, D. Transcription factor NF-κB associates with microtubules and stimulates apoptosis in response to suppression of microtubule dynamics in MCF-7 cells. Biochem. Pharmacol., 2015, 93(3), 277-289. doi: 10.1016/j.bcp.2014.12.007 PMID: 25536174
  35. Genin, M.; Clement, F.; Fattaccioli, A.; Raes, M.; Michiels, C. M1 and M2 macrophages derived from THP-1 cells differentially modulate the response of cancer cells to etoposide. BMC Cancer, 2015, 15(1), 577. doi: 10.1186/s12885-015-1546-9 PMID: 26253167
  36. Wang, T.H.; Wang, H.S.; Soong, Y.K. Paclitaxel-induced cell death. Cancer, 2000, 88(11), 2619-2628. doi: 10.1002/1097-0142(20000601)88:113.0.CO;2-J PMID: 10861441
  37. Liu, K.; Cang, S.; Ma, Y.; Chiao, J.W. Synergistic effect of paclitaxel and epigenetic agent phenethyl isothiocyanate on growth inhibition, cell cycle arrest and apoptosis in breast cancer cells. Cancer Cell Int., 2013, 13(1), 10. doi: 10.1186/1475-2867-13-10 PMID: 23388416
  38. Hao, Y.; Baker, D.; ten Dijke, P. TGF-β-Mediated epithelial-mesenchymal transition and cancer metastasis. Int. J. Mol. Sci., 2019, 20(11), 2767. doi: 10.3390/ijms20112767 PMID: 31195692
  39. Borges, G.A.; Elias, S.T.; Amorim, B.; de Lima, C.L.; Coletta, R.D.; Castilho, R.M.; Squarize, C.H.; Guerra, E.N.S. Curcumin downregulates the PI3K–AKT–MTOR pathway and inhibits growth and progression in head and neck cancer cells. Phytother. Res., 2020, 34(12), 3311-3324. doi: 10.1002/ptr.6780 PMID: 32628350
  40. Hart, J.R.; Liao, L.; Yates, J.R., III; Vogt, P.K. Essential role of Stat3 in PI3K-induced oncogenic transformation. Proc. Natl. Acad. Sci. USA, 2011, 108(32), 13247-13252. doi: 10.1073/pnas.1110486108 PMID: 21788516
  41. Wang, W.; Nag, S.; Zhang, R. Targeting the NFκB signaling pathways for breast cancer prevention and therapy. Curr. Med. Chem., 2014, 22(2), 264-289. doi: 10.2174/0929867321666141106124315 PMID: 25386819
  42. Lim, J.W.; Kim, H.; Kim, K.H. Nuclear factor-kappaB regulates cyclooxygenase-2 expression and cell proliferation in human gastric cancer cells. Lab. Invest., 2001, 81(3), 349-360. doi: 10.1038/labinvest.3780243 PMID: 11310828
  43. Nowak, M.; Klink, M. The role of tumor-associated macrophages in the progression and chemoresistance of ovarian cancer. Cells, 2020, 9(5), 1299. doi: 10.3390/cells9051299
  44. Li, H.; Yang, P.; Wang, J. HLF regulates ferroptosis, development and chemoresistance of triple-negative breast cancer by activating tumor cell-macrophage crosstalk. J. Hematol. Oncol., 2022, 15(1), 2. doi: 10.1186/s13045-021-01223-x
  45. Song, M.; Yeku, O.O. Rafiq, S Tumor derived UBR5 promotes ovarian cancer growth and metastasis through inducing immunosuppressive macrophages. Nat. Commun., 2020, 11(1), 6298. doi: 10.1038/s41467-020-20140-0
  46. Wang, N.; Wang, S.; Wang, X.; Zheng, Y.; Yang, B.; Zhang, J.; Pan, B.; Gao, J.; Wang, Z. Research trends in pharmacological modulation of tumor‐associated macrophages. Clin. Transl. Med., 2021, 11(1), e288. doi: 10.1002/ctm2.288 PMID: 33463063
  47. Li, H.; Luo, F.; Jiang, X.; Zhang, W.; Xiang, T.; Pan, Q.; Cai, L.; Zhao, J.; Weng, D.; Li, Y.; Dai, Y.; Sun, F.; Yang, C.; Huang, Y.; Yang, J.; Tang, Y.; Han, Y.; He, M.; Zhang, Y.; Song, L.; Xia, J.C. CircITGB6 promotes ovarian cancer cisplatin resistance by resetting tumor-associated macrophage polarization toward the M2 phenotype. J. Immunother. Cancer, 2022, 10(3), e004029. doi: 10.1136/jitc-2021-004029 PMID: 35277458
  48. Larionova, I.; Cherdyntseva, N.; Liu, T.; Patysheva, M.; Rakina, M.; Kzhyshkowska, J. Interaction of tumor-associated macrophages and cancer chemotherapy. OncoImmunology, 2019, 8(7), 1596004. doi: 10.1080/2162402X.2019.1596004
  49. Zhang, G.; Tao, X.; Ji, B.; Gong, J. Hypoxia-driven m2-polarized macrophages facilitate cancer aggressiveness and temozolomide resistance in glioblastoma. Oxid. Med. Cell. Longev., 2022, 1614336. doi: 10.1155/2022/1614336
  50. Oelschlaegel, D.; Weiss Sadan, T.; Salpeter, S. Cathepsin inhibition modulates metabolism and polarization of tumor-associated macrophages. Cancers, 2020, 12(9), 2579. doi: 10.3390/cancers12092579
  51. Olson, O.C.; Kim, H.; Quail, D.F.; Foley, E.A.; Joyce, J.A. Tumor-associated macrophages suppress the cytotoxic activity of antimitotic agents. Cell Rep., 2017, 19(1), 101-113. doi: 10.1016/j.celrep.2017.03.038 PMID: 28380350
  52. Mantovani, A.; Allavena, P. The interaction of anticancer therapies with tumor-associated macrophages. J. Exp. Med., 2015, 212(4), 435-445. doi: 10.1084/jem.20150295 PMID: 25753580
  53. Peng, D.; Fu, M.; Wang, M.; Wei, Y.; Wei, X. Targeting TGF-β signal transduction for fibrosis and cancer therapy. Mol. Cancer, 2022, 21(1), 104. doi: 10.1186/s12943-022-01569-x
  54. Xie, F.; Ling, L.; Van Dam, H.; Zhou, F.; Zhang, L. TGF-β signaling in cancer metastasis. Acta Biochim. Biophys. Sin. (Shanghai), 2018, 50(1), 121-132. doi: 10.1093/abbs/gmx123 PMID: 29190313
  55. Derynck, R.; Turley, S.J.; Akhurst, R.J. TGFβ biology in cancer progression and immunotherapy. Nat. Rev. Clin. Oncol., 2021, 18(1), 9-34. doi: 10.1038/s41571-020-0403-1 PMID: 32710082
  56. Zhao, M.; Mishra, L.; Deng, C.X. The role of TGF-β/SMAD4 signaling in cancer. Int. J. Biol. Sci., 2018, 14(2), 111-123. doi: 10.7150/ijbs.23230
  57. Hata, A.; Chen, Y.G. TGF-β signaling from receptors to smads. Cold Spring Harb. Perspect. Biol., 2016, 8(9), a022061. doi: 10.1101/cshperspect.a022061
  58. Tzavlaki, K.; Moustakas, A. TGF-β Signaling. Biomolecules, 2020, 10(3), 487. doi: 10.3390/biom10030487 PMID: 32210029
  59. Gabrilovich, D.I.; Ostrand-Rosenberg, S.; Bronte, V. Coordinated regulation of myeloid cells by tumours. Nat. Rev. Immunol., 2012, 12(4), 253-268. doi: 10.1038/nri3175 PMID: 22437938
  60. Su, Y.L.; Banerjee, S.; White, S.; Kortylewski, M. STAT3 in tumor-associated myeloid cells: multitasking to disrupt immunity. Int. J. Mol. Sci., 2018, 19(6), 1803. doi: 10.3390/ijms19061803 PMID: 29921770
  61. Peng, P.; Zhu, H.; Liu, D. TGFBI secreted by tumor-associated macrophages promotes glioblastoma stem cell-driven tumor growth via integrin αvβ5-Src-Stat3 signaling. Theranostics, 2022, 12(9), 4221-4236. doi: 10.7150/thno.69605
  62. Nadella, V.; Garg, M.; Kapoor, S.; Barwal, T.S.; Jain, A.; Prakash, H. Emerging neo adjuvants for harnessing therapeutic potential of M1 tumor associated macrophages (TAM) against solid tumors: Enusage of plasticity. Ann. Transl. Med., 2020, 8(16), 1029. doi: 10.21037/atm-20-695 PMID: 32953829
  63. Li, H. Chen, A.; Yuan, Q.; Chen, W.; Zhong, H.; Teng, M.; Xu, C.; Qiu, Y.; Cao, J. NF-κB/Twist axis is involved in chysin inhibition of ovarian cancer stem cell features induced by co-treatment of TNF-α and TGF-β. Int. J. Clin. Exp. Pathol., 2019, 12(1), 101-112. PMID: 31933724
  64. Vergani, E.; Dugo, M.; Cossa, M.; Frigerio, S.; Di Guardo, L.; Gallino, G.; Mattavelli, I.; Vergani, B.; Lalli, L.; Tamborini, E.; Valeri, B.; Gargiuli, C.; Shahaj, E.; Ferrarini, M.; Ferrero, E.; Gomez Lira, M.; Huber, V.; Del Vecchio, M.; Sensi, M.; Leone, B.E.; Santinami, M.; Rivoltini, L.; Rodolfo, M.; Vallacchi, V. miR-146a-5p impairs melanoma resistance to kinase inhibitors by targeting COX2 and regulating NFkB-mediated inflammatory mediators. Cell Commun. Signal., 2020, 18(1), 156. doi: 10.1186/s12964-020-00601-1 PMID: 32967672
  65. Allegra, A.; Mirabile, G.; Ettari, R.; Pioggia, G.; Gangemi, S. The impact of curcumin on immune response: An Immunomodulatory strategy to treat sepsis. Int. J. Mol. Sci., 2022, 23(23), 14710. doi: 10.3390/ijms232314710
  66. Bose, S.; Panda, A.K.; Mukherjee, S.; Sa, G. Curcumin and tumor immune-editing: Resurrecting the immune system. Cell Div., 2015, 10, 6. doi: 10.1186/s13008-015-0012-z
  67. Paul, S.; Sa, G. Curcumin as an adjuvant to cancer immunotherapy. Front. Oncol., 2021, 11, 675923. doi: 10.3389/fonc.2021.675923
  68. Jiang, M.; Qi, Y.; Huang, W.; Lin, Y.; Li, B. Curcumin Reprograms TAMs from a protumor phenotype towards an antitumor phenotype via inhibiting MAO-A/STAT6 Pathway. Cells, 2022, 11(21), 3473. doi: 10.3390/cells11213473 PMID: 36359867
  69. Oh, J.G.; Hwang, D.J.; Heo, T.H. Direct regulation of IL-2 by curcumin. Biochem. Biophys. Res. Commun., 2018, 495(1), 300-305. doi: 10.1016/j.bbrc.2017.11.039 PMID: 29127008
  70. Zhang, X.; Tian, W.; Cai, X.; Wang, X.; Dang, W.; Tang, H.; Cao, H.; Wang, L.; Chen, T. Hydrazinocurcumin Encapsuled nanoparticles "re-educate" tumor-associated macrophages and exhibit anti-tumor effects on breast cancer following STAT3 suppression. PLoS One, 2013, 8(6), e65896. doi: 10.1371/journal.pone.0065896 PMID: 23825527
  71. Shiri, S.; Alizadeh, A.M.; Baradaran, B.; Farhanghi, B.; Shanehbandi, D.; Khodayari, S.; Khodayari, H.; Tavassoli, A. Dendrosomal curcumin suppresses metastatic breast cancer in mice by changing m1/m2 macrophage balance in the tumor microenvironment. Asian Pac. J. Cancer Prev., 2015, 16(9), 3917-3922. doi: 10.7314/APJCP.2015.16.9.3917 PMID: 25987060
  72. Xu, L.; Wang, X.; Wang, X.Y.; Yao, Q.H. Chen, YB signaling pathway to repair intestinal mucosal injury induced by 5-FU chemotherapy for colon. Zhongguo Zhongyao Zazhi, 2021, 46(3), 670-677. doi: 10.19540/j.cnki.cjcmm.20201106.401
  73. Weir, N.M.; Selvendiran, K.; Kutala, V.K.; Tong, L.; Vishwanath, S.; Rajaram, M.; Tridandapani, S.; Anant, S.; Kuppusamy, P. Curcumin induces G2/M arrest and apoptosis in cisplatin-resistant human ovarian cancer cells by modulating akt and p38 mAPK. Cancer Biol. Ther., 2007, 6(2), 178-184. doi: 10.4161/cbt.6.2.3577 PMID: 17218783
  74. Zhao, H.Y.; Zhang, Y.Y.; Xing, T. M2 macrophages, but not M1 macrophages, support megakaryopoiesis by upregulating PI3K-AKT pathway activity. Signal Transduct. Target. Ther., 2021, 6(1), 234. doi: 10.1038/s41392-021-00627-y
  75. Zhao, S.J.; Kong, F.Q.; Jie, J. Macrophage MSR1 promotes BMSC osteogenic differentiation and M2-like polarization by activating PI3K/AKT/GSK3β/β-catenin pathway. Theranostics, 2020, 10(1), 17-35. doi: 10.7150/thno.36930
  76. Yu, L.L.; Wu, J.G.; Dai, N.; Yu, H.G.; Si, J.M. Curcumin reverses chemoresistance of human gastric cancer cells by downregulating the NF-κB transcription factor. Oncol. Rep., 2011, 26(5), 1197-1203. doi: 10.3892/or.2011.1410 PMID: 21811763

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Bentham Science Publishers