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Combination treatment of berberine and solid lipid curcumin particles increased cell death and inhibited PI3K/Akt/mTOR pathway of human cultured glioblastoma cells more effectively than did individual treatments


Autoři: Panchanan Maiti aff001;  Alexandra Plemmons aff001;  Gary L. Dunbar aff001
Působiště autorů: Field Neurosciences Institute Laboratory for Restorative Neurology, Central Michigan University, Mt. Pleasant, MI, United States of America aff001;  Program in Neuroscience, Central Michigan University, Mt. Pleasant, MI, United States of America aff002;  Department of Psychology, Central Michigan University, Mt. Pleasant, MI, United States of America aff003;  Field Neurosciences Institute, Ascension of St. Mary’s Hospital, Saginaw, MI, United States of America aff004;  Department of Biology, Saginaw Valley State University, Saginaw, MI, United States of America aff005
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0225660

Souhrn

The treatment of glioblastoma is challenging for the clinician, due to its chemotherapeutic resistance. Recent findings suggest that targeting glioblastoma using anti-cancer natural polyphenols is a promising strategy. In this context, curcumin and berberine have been shown to have potent anti-cancer and anti-inflammatory effects against several malignancies. Due to the poor solubility and limited bioavailability, these compounds have limited efficacy for treating cancer. However, use of a formulation of curcumin with higher bioavailability or combining it with berberine as a co-treatment may be proving to be more efficacious against cancer. Recently, we demonstrated that solid lipid curcumin particles (SLCPs) provided more bioavailability and anti-cancer effects in cultured glioblastoma cells than did natural curcumin. Interestingly, a combination of curcumin and berberine has proven to be more effective in inhibiting growth and proliferation of cancer in the liver, breast, lung, bone and blood. However, the effect of combining these drugs for treating glioblastoma, especially with respect to its effect on activating the PI3K/Akt/mTOR pathways has not been studied. Therefore, we decided to assess the co-treatment effects of these drugs on two different glioblastoma cell lines (U-87MG and U-251MG) and neuroblastoma cell lines (SH-SY5Y) derived from human tissue. In this study, we compared single and combination (1:5) treatment of SLCP (20 μM) and berberine (100 μM) on measures of cell viability, cell death markers, levels of c-Myc and p53, along with biomarkers of the PI3K/Akt/mTOR pathways after 24–48 h of incubation. We found that co-treatment of SLCP and berberine produced more glioblastoma cell death, more DNA fragmentation, and significantly decreased ATP levels and reduced mitochondrial membrane potential than did single treatments in both glioblastoma cells lines. In addition, we observed that co-treatment inhibited the PI3K/Akt/mTOR pathway more efficiently than their single treatments. Our study suggests that combination treatments of SLCP and berberine may be a promising strategy to reduce or prevent glioblastoma growth in comparison to individual treatments using either compound.

Klíčová slova:

Apoptosis – Cancer treatment – Cell death – Cell staining – DNA fragmentation – Drug therapy – Fluorescence microscopy – Mitochondria


Zdroje

1. Sordillo LA, Sordillo PP, Helson L. Curcumin for the Treatment of Glioblastoma. Anticancer Res. 2015;35(12):6373–8. 26637846

2. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. The New England journal of medicine. 2005;352(10):987–96. doi: 10.1056/NEJMoa043330 15758009

3. Laws ER, Parney IF, Huang W, Anderson F, Morris AM, Asher A, et al. Survival following surgery and prognostic factors for recently diagnosed malignant glioma: data from the Glioma Outcomes Project. Journal of neurosurgery. 2003;99(3):467–73. doi: 10.3171/jns.2003.99.3.0467 12959431

4. DeAngelis LM. Brain tumors. The New England journal of medicine. 2001;344(2):114–23. doi: 10.1056/NEJM200101113440207 11150363

5. Mirimanoff RO, Gorlia T, Mason W, Van den Bent MJ, Kortmann RD, Fisher B, et al. Radiotherapy and temozolomide for newly diagnosed glioblastoma: recursive partitioning analysis of the EORTC 26981/22981-NCIC CE3 phase III randomized trial. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2006;24(16):2563–9.

6. Mrugala MM, Chamberlain MC. Mechanisms of disease: temozolomide and glioblastoma—look to the future. Nature clinical practice Oncology. 2008;5(8):476–86. doi: 10.1038/ncponc1155 18542116

7. Yin H, Zhou Y, Wen C, Zhou C, Zhang W, Hu X, et al. Curcumin sensitizes glioblastoma to temozolomide by simultaneously generating ROS and disrupting AKT/mTOR signaling. Oncol Rep. 2014;32(4):1610–6. doi: 10.3892/or.2014.3342 25050915

8. Freudlsperger C, Greten J, Schumacher U. Curcumin induces apoptosis in human neuroblastoma cells via inhibition of NFkappaB. Anticancer research. 2008;28(1A):209–14. 18383847

9. Kuo CL, Wu SY, Ip SW, Wu PP, Yu CS, Yang JS, et al. Apoptotic death in curcumin-treated NPC-TW 076 human nasopharyngeal carcinoma cells is mediated through the ROS, mitochondrial depolarization and caspase-3-dependent signaling responses. International journal of oncology. 2011;39(2):319–28. doi: 10.3892/ijo.2011.1057 21617861

10. Liontas A, Yeger H. Curcumin and resveratrol induce apoptosis and nuclear translocation and activation of p53 in human neuroblastoma. Anticancer research. 2004;24(2B):987–98. 15161054

11. Dhandapani KM, Mahesh VB, Brann DW. Curcumin suppresses growth and chemoresistance of human glioblastoma cells via AP-1 and NFkappaB transcription factors. Journal of neurochemistry. 2007;102(2):522–38. doi: 10.1111/j.1471-4159.2007.04633.x 17596214

12. Prasad S, Aggarwal BB. Turmeric, the Golden Spice: From Traditional Medicine to Modern Medicine. In: Benzie IFF, Wachtel-Galor S, editors. Herbal Medicine: Biomolecular and Clinical Aspects. 2nd ed. Boca Raton (FL)2011.

13. Luthra PM, Lal N. Prospective of curcumin, a pleiotropic signalling molecule from Curcuma longa in the treatment of Glioblastoma. European journal of medicinal chemistry. 2016;109:23–35. doi: 10.1016/j.ejmech.2015.11.049 26748069

14. Gersey ZC, Rodriguez GA, Barbarite E, Sanchez A, Walters WM, Ohaeto KC, et al. Curcumin decreases malignant characteristics of glioblastoma stem cells via induction of reactive oxygen species. BMC cancer. 2017;17(1):99. doi: 10.1186/s12885-017-3058-2 28160777

15. Ravindran J, Prasad S, Aggarwal BB. Curcumin and cancer cells: how many ways can curry kill tumor cells selectively? AAPS J. 2009;11(3):495–510. doi: 10.1208/s12248-009-9128-x 19590964

16. Klinger NV, Mittal S. Therapeutic Potential of Curcumin for the Treatment of Brain Tumors. Oxidative medicine and cellular longevity. 2016;2016:9324085. doi: 10.1155/2016/9324085 27807473

17. Weissenberger J, Priester M, Bernreuther C, Rakel S, Glatzel M, Seifert V, et al. Dietary curcumin attenuates glioma growth in a syngeneic mouse model by inhibition of the JAK1,2/STAT3 signaling pathway. Clinical cancer research: an official journal of the American Association for Cancer Research. 2010;16(23):5781–95.

18. Wang Y, Ying X, Xu H, Yan H, Li X, Tang H. The functional curcumin liposomes induce apoptosis in C6 glioblastoma cells and C6 glioblastoma stem cells in vitro and in animals. International journal of nanomedicine. 2017;12:1369–84. doi: 10.2147/IJN.S124276 28260885

19. Gupta SC, Prasad S, Kim JH, Patchva S, Webb LJ, Priyadarsini IK, et al. Multitargeting by curcumin as revealed by molecular interaction studies. Nat Prod Rep. 2011;28(12):1937–55. doi: 10.1039/c1np00051a 21979811

20. Tong L, Xie C, Wei Y, Qu Y, Liang H, Zhang Y, et al. Antitumor Effects of Berberine on Gliomas via Inactivation of Caspase-1-Mediated IL-1beta and IL-18 Release. Front Oncol. 2019;9:364. doi: 10.3389/fonc.2019.00364 31139563

21. Dai W, Mu L, Cui Y, Li Y, Chen P, Xie H, et al. Berberine Promotes Apoptosis of Colorectal Cancer via Regulation of the Long Non-Coding RNA (lncRNA) Cancer Susceptibility Candidate 2 (CASC2)/AU-Binding Factor 1 (AUF1)/B-Cell CLL/Lymphoma 2 (Bcl-2) Axis. Med Sci Monit. 2019;25:730–8. doi: 10.12659/MSM.912082 30681073

22. Li J, Liu F, Jiang S, Liu J, Chen X, Zhang S, et al. Berberine hydrochloride inhibits cell proliferation and promotes apoptosis of non-small cell lung cancer via the suppression of the MMP2 and Bcl-2/Bax signaling pathways. Oncol Lett. 2018;15(5):7409–14. doi: 10.3892/ol.2018.8249 29725453

23. Lu W, Du S, Wang J. Berberine inhibits the proliferation of prostate cancer cells and induces G(0)/G(1) or G(2)/M phase arrest at different concentrations. Mol Med Rep. 2015;11(5):3920–4. doi: 10.3892/mmr.2014.3139 25572870

24. Jin P, Zhang C, Li N. Berberine exhibits antitumor effects in human ovarian cancer cells. Anticancer Agents Med Chem. 2015;15(4):511–6. doi: 10.2174/1871520614666141226124110 25544381

25. Wang J, Qi Q, Feng Z, Zhang X, Huang B, Chen A, et al. Berberine induces autophagy in glioblastoma by targeting the AMPK/mTOR/ULK1-pathway. Oncotarget. 2016;7(41):66944–58. doi: 10.18632/oncotarget.11396 27557493

26. Jin F, Xie T, Huang X, Zhao X. Berberine inhibits angiogenesis in glioblastoma xenografts by targeting the VEGFR2/ERK pathway. Pharm Biol. 2018;56(1):665–71. doi: 10.1080/13880209.2018.1548627 31070539

27. Agnarelli A, Natali M, Garcia-Gil M, Pesi R, Tozzi MG, Ippolito C, et al. Cell-specific pattern of berberine pleiotropic effects on different human cell lines. Sci Rep. 2018;8(1):10599. doi: 10.1038/s41598-018-28952-3 30006630

28. Maiti P, Scott J, Sengupta D, Al-Gharaibeh A, Dunbar GL. Curcumin and Solid Lipid Curcumin Particles Induce Autophagy, but Inhibit Mitophagy and the PI3K-Akt/mTOR Pathway in Cultured Glioblastoma Cells. Int J Mol Sci. 2019;20(2).

29. Wang K, Zhang C, Bao J, Jia X, Liang Y, Wang X, et al. Synergistic chemopreventive effects of curcumin and berberine on human breast cancer cells through induction of apoptosis and autophagic cell death. Sci Rep. 2016;6:26064. doi: 10.1038/srep26064 27263652

30. Balakrishna A, Kumar MH. Evaluation of Synergetic Anticancer Activity of Berberine and Curcumin on Different Models of A549, Hep-G2, MCF-7, Jurkat, and K562 Cell Lines. Biomed Res Int. 2015;2015:354614. doi: 10.1155/2015/354614 26247019

31. DiSilvestro RA, Joseph E, Zhao S, Bomser J. Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people. Nutr J. 2012;11:79. doi: 10.1186/1475-2891-11-79 23013352

32. Nahar PP, Slitt AL, Seeram NP. Anti-Inflammatory Effects of Novel Standardized Solid Lipid Curcumin Formulations. Journal of medicinal food. 2015;18(7):786–92. doi: 10.1089/jmf.2014.0053 25490740

33. Cox KH, Pipingas A, Scholey AB. Investigation of the effects of solid lipid curcumin on cognition and mood in a healthy older population. J Psychopharmacol. 2015;29(5):642–51. doi: 10.1177/0269881114552744 25277322

34. Ma QL, Zuo X, Yang F, Ubeda OJ, Gant DJ, Alaverdyan M, et al. Curcumin suppresses soluble tau dimers and corrects molecular chaperone, synaptic, and behavioral deficits in aged human tau transgenic mice. J Biol Chem. 2013;288(6):4056–65. doi: 10.1074/jbc.M112.393751 23264626

35. Maiti P, Dunbar GL. Comparative Neuroprotective Effects of Dietary Curcumin and Solid Lipid Curcumin Particles in Cultured Mouse Neuroblastoma Cells after Exposure to Abeta42. Int J Alzheimers Dis. 2017;2017:4164872. doi: 10.1155/2017/4164872 28567323

36. Koronyo Y, Biggs D, Barron E, Boyer DS, Pearlman JA, Au WJ, et al. Retinal amyloid pathology and proof-of-concept imaging trial in Alzheimer's disease. JCI Insight. 2017;2(16).

37. Maiti P, Hall TC, Paladugu L, Kolli N, Learman C, Rossignol J, et al. A comparative study of dietary curcumin, nanocurcumin, and other classical amyloid-binding dyes for labeling and imaging of amyloid plaques in brain tissue of 5x-familial Alzheimer's disease mice. Histochemistry and cell biology. 2016.

38. Maiti P, Lomakin A, Benedek GB, Bitan G. Despite its role in assembly, methionine 35 is not necessary for amyloid beta-protein toxicity. J Neurochem. 2010;113(5):1252–62. doi: 10.1111/j.1471-4159.2010.06692.x 20345758

39. Maiti P, Piacentini R, Ripoli C, Grassi C, Bitan G. Surprising toxicity and assembly behaviour of amyloid beta-protein oxidized to sulfone. The Biochemical journal. 2011;433(2):323–32. doi: 10.1042/BJ20101391 21044048

40. Roychaudhuri R, Zheng X, Lomakin A, Maiti P, Condron MM, Benedek GB, et al. Role of Species-Specific Primary Structure Differences in Abeta42 Assembly and Neurotoxicity. ACS chemical neuroscience. 2015;6(12):1941–55. doi: 10.1021/acschemneuro.5b00180 26421877

41. Nandhakumar S, Parasuraman S, Shanmugam MM, Rao KR, Chand P, Bhat BV. Evaluation of DNA damage using single-cell gel electrophoresis (Comet Assay). J Pharmacol Pharmacother. 2011;2(2):107–11. doi: 10.4103/0976-500X.81903 21772771

42. Olive PL, Banath JP. The comet assay: a method to measure DNA damage in individual cells. Nat Protoc. 2006;1(1):23–9. doi: 10.1038/nprot.2006.5 17406208

43. Azqueta A, Slyskova J, Langie SA, O'Neill Gaivao I, Collins A. Comet assay to measure DNA repair: approach and applications. Frontiers in genetics. 2014;5:288. doi: 10.3389/fgene.2014.00288 25202323

44. Rastogi RP, Singh SP, Hader DP, Sinha RP. Detection of reactive oxygen species (ROS) by the oxidant-sensing probe 2',7'-dichlorodihydrofluorescein diacetate in the cyanobacterium Anabaena variabilis PCC 7937. Biochemical and biophysical research communications. 2010;397(3):603–7. doi: 10.1016/j.bbrc.2010.06.006 20570649

45. Kasibhatla S, Amarante-Mendes GP, Finucane D, Brunner T, Bossy-Wetzel E, Green DR. Analysis of DNA fragmentation using agarose gel electrophoresis. CSH Protoc. 2006;2006(1).

46. Vengoji R, Macha MA, Batra SK, Shonka NA. Natural products: a hope for glioblastoma patients. Oncotarget. 2018;9(31):22194–219. doi: 10.18632/oncotarget.25175 29774132

47. Desai V, Bhushan A. Natural Bioactive Compounds: Alternative Approach to the Treatment of Glioblastoma Multiforme. Biomed Res Int. 2017;2017:9363040. doi: 10.1155/2017/9363040 29359162

48. Guerra AR, Duarte MF, Duarte IF. Targeting Tumor Metabolism with Plant-Derived Natural Products: Emerging Trends in Cancer Therapy. J Agric Food Chem. 2018;66(41):10663–85. doi: 10.1021/acs.jafc.8b04104 30227704

49. McCubrey JA, Abrams SL, Lertpiriyapong K, Cocco L, Ratti S, Martelli AM, et al. Effects of berberine, curcumin, resveratrol alone and in combination with chemotherapeutic drugs and signal transduction inhibitors on cancer cells-Power of nutraceuticals. Adv Biol Regul. 2018;67:190–211. doi: 10.1016/j.jbior.2017.09.012 28988970

50. Chamberlain MC. Temozolomide: therapeutic limitations in the treatment of adult high-grade gliomas. Expert Rev Neurother. 2010;10(10):1537–44. doi: 10.1586/ern.10.32 20925470

51. Lee SY. Temozolomide resistance in glioblastoma multiforme. Genes Dis. 2016;3(3):198–210. doi: 10.1016/j.gendis.2016.04.007 30258889

52. Jiapaer S, Furuta T, Tanaka S, Kitabayashi T, Nakada M. Potential Strategies Overcoming the Temozolomide Resistance for Glioblastoma. Neurol Med Chir (Tokyo). 2018;58(10):405–21.

53. Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharm. 2007;4(6):807–18. doi: 10.1021/mp700113r 17999464

54. Godugu C, Patel AR, Doddapaneni R, Somagoni J, Singh M. Approaches to improve the oral bioavailability and effects of novel anticancer drugs berberine and betulinic acid. PLoS One. 2014;9(3):e89919. doi: 10.1371/journal.pone.0089919 24614362

55. Maiti P, Al-Gharaibeh A, Kolli N, Dunbar GL. Solid Lipid Curcumin Particles Induce More DNA Fragmentation and Cell Death in Cultured Human Glioblastoma Cells than Does Natural Curcumin. Oxid Med Cell Longev. 2017;2017:9656719. doi: 10.1155/2017/9656719 29359011

56. Maiti P, Dunbar GL. Use of Curcumin, a Natural Polyphenol for Targeting Molecular Pathways in Treating Age-Related Neurodegenerative Diseases. Int J Mol Sci. 2018;19(6).

57. Maiti P, Hall TC, Paladugu L, Kolli N, Learman C, Rossignol J, et al. A comparative study of dietary curcumin, nanocurcumin, and other classical amyloid-binding dyes for labeling and imaging of amyloid plaques in brain tissue of 5x-familial Alzheimer's disease mice. Histochem Cell Biol. 2016;146(5):609–25. doi: 10.1007/s00418-016-1464-1 27406082

58. Maiti P, Paladugu L, Dunbar GL. Solid lipid curcumin particles provide greater anti-amyloid, anti-inflammatory and neuroprotective effects than curcumin in the 5xFAD mouse model of Alzheimer's disease. BMC Neurosci. 2018;19(1):7. doi: 10.1186/s12868-018-0406-3 29471781

59. Liu Q, Xu X, Zhao M, Wei Z, Li X, Zhang X, et al. Berberine induces senescence of human glioblastoma cells by downregulating the EGFR-MEK-ERK signaling pathway. Mol Cancer Ther. 2015;14(2):355–63. doi: 10.1158/1535-7163.MCT-14-0634 25504754

60. Kunwar A, Barik A, Mishra B, Rathinasamy K, Pandey R, Priyadarsini KI. Quantitative cellular uptake, localization and cytotoxicity of curcumin in normal and tumor cells. Biochimica et biophysica acta. 2008;1780(4):673–9. doi: 10.1016/j.bbagen.2007.11.016 18178166

61. Syng-Ai C, Kumari AL, Khar A. Effect of curcumin on normal and tumor cells: role of glutathione and bcl-2. Molecular cancer therapeutics. 2004;3(9):1101–8. 15367704

62. Shishodia S, Amin HM, Lai R, Aggarwal BB. Curcumin (diferuloylmethane) inhibits constitutive NF-kappaB activation, induces G1/S arrest, suppresses proliferation, and induces apoptosis in mantle cell lymphoma. Biochemical pharmacology. 2005;70(5):700–13. doi: 10.1016/j.bcp.2005.04.043 16023083

63. Sawai H, Domae N. Discrimination between primary necrosis and apoptosis by necrostatin-1 in Annexin V-positive/propidium iodide-negative cells. Biochemical and biophysical research communications. 2011;411(3):569–73. doi: 10.1016/j.bbrc.2011.06.186 21763280

64. Singh NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res. 1988;175(1):184–91. doi: 10.1016/0014-4827(88)90265-0 3345800

65. Sivandzade F, Bhalerao A, Cucullo L. Analysis of the Mitochondrial Membrane Potential Using the Cationic JC-1 Dye as a Sensitive Fluorescent Probe. Bio Protoc. 2019;9(1).

66. Salvioli S, Ardizzoni A, Franceschi C, Cossarizza A. JC-1, but not DiOC6(3) or rhodamine 123, is a reliable fluorescent probe to assess delta psi changes in intact cells: implications for studies on mitochondrial functionality during apoptosis. FEBS Lett. 1997;411(1):77–82. doi: 10.1016/s0014-5793(97)00669-8 9247146

67. Elmore S. Apoptosis: a review of programmed cell death. Toxicologic pathology. 2007;35(4):495–516. doi: 10.1080/01926230701320337 17562483

68. Rivlin N, Brosh R, Oren M, Rotter V. Mutations in the p53 Tumor Suppressor Gene: Important Milestones at the Various Steps of Tumorigenesis. Genes & cancer. 2011;2(4):466–74.

69. Kaposi-Novak P, Libbrecht L, Woo HG, Lee YH, Sears NC, Coulouarn C, et al. Central role of c-Myc during malignant conversion in human hepatocarcinogenesis. Cancer research. 2009;69(7):2775–82. doi: 10.1158/0008-5472.CAN-08-3357 19276364

70. Dobbin ZC, Landen CN. The importance of the PI3K/AKT/MTOR pathway in the progression of ovarian cancer. Int J Mol Sci. 2013;14(4):8213–27. doi: 10.3390/ijms14048213 23591839


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