The Journal of Practical Medicine >
Impact of spermidine on proliferation and apoptosis in diffuse large B⁃cell lymphoma cell lines
Received date: 2024-04-07
Online published: 2024-11-25
Objective To investigate the impact of spermidine on proliferation and apoptosis of diffuse large B?cell lymphoma (DLBCL) cell lines. Methods The impact of spermidine on cellular growth was assessed using a CCK?8 assay. Flow cytometry was employed to investigate the effects of spermidine on the proliferation and cell cycle dynamics of DLBCL cell lines, as well as to evaluate its influence on apoptosis in DLBCL cell lines, mouse splenocytes, and peripheral blood mononuclear cells (PBMCs) derived from healthy individuals. Western blot analysis was conducted to examine alterations in protein expression levels associated with apoptosis and the cell cycle following treatment with spermidine. Results The CCK?8 assay revealed a significant inhibitory effect of spermidine on DLBCL cell growth (P < 0.001). Flow cytometric analysis demonstrated that spermidine had no impact on the proliferation or cell cycle of DLBCL cells, but significantly induced apoptosis (P < 0.001). Spermidine exhibited a pro?apoptotic effect on mouse splenocytes (P < 0.01), albeit weaker compared to its effect on DLBCL cells (P < 0.001), and showed no significant pro?apoptotic effect on PBMCs. Western blot results indicated that spermidine did not influence the expression levels of cell cycle proteins CDK2 and CDK4, but enhanced the activation of Caspase?9 in A20 cells and Caspase?8 in OCI?Ly3 cells. Conclusion Spermidine induces apoptosis and suppresses cell growth in DLBCL cell lines, while exhibiting diminished or absent pro-apoptotic effects on mouse splenocytes and healthy human PBMCs, suggesting its potential as a specific inhibitor for the growth of DLBCL cell lines in vivo.
Key words: spermidine; diffuse large B-cell lymphoma; proliferation; apoptosis
Bing′er WU , Qing LI , Kerong YANG , Jian ZHANG , Yi YU , Lei LEI , Bo. HU . Impact of spermidine on proliferation and apoptosis in diffuse large B⁃cell lymphoma cell lines[J]. The Journal of Practical Medicine, 2024 , 40(22) : 3130 -3137 . DOI: 10.3969/j.issn.1006-5725.2024.22.003
| 1 | NING N, ZHANG S, WU Q, et al. Inhibition of acylglycerol kinase sensitizes DLBCL to venetoclax via upregulation of FOXO1-mediated BCL-2 expression[J]. Theranostics, 2022, 12(12): 5537-5550. doi:10.7150/thno.72786 |
| 2 | YE X, WANG L, NIE M, et al. A single-cell atlas of diffuse large B cell lymphoma[J]. Cell Reports, 2022, 39(3): 110713. doi:10.1016/j.celrep.2022.110713 |
| 3 | 范丹丹,胡茂贵,丁凯阳,等. 利妥昔单抗联合CHOP 方案治疗在初治弥漫大B细胞淋巴瘤患者中的疗效和安全性[J]. 实用医学杂志, 2023, 39(8): 1022-1028. |
| 4 | ZHANG M C, TIAN S, FU D, et al. Genetic subtype-guided immunochemotherapy in diffuse large B cell lymphoma: The randomized GUIDANCE-01 trial[J]. Cancer Cell, 2023, 41(10): 1705-1716.e5. doi:10.1016/j.ccell.2023.09.004 |
| 5 | WESTIN J, SEHN L H. CAR T cells as a second-line therapy for large B-cell lymphoma: A paradigm shift?[J]. Blood, 2022, 139(18): 2737-2746. doi:10.1182/blood.2022015789 |
| 6 | MU?OZ-ESPARZA N C, LATORRE-MORATALLA M L, COMAS-BASTé O, et al. Polyamines in Food[J]. Front Nutr, 2019, 6: 108. doi:10.3389/fnut.2019.00108 |
| 7 | CASERO R A JR, MURRAY STEWART T, PEGG A E. Polyamine metabolism and cancer: Treatments, challenges and opportunities[J]. Nat Rev Cancer, 2018, 18(11): 681-695. doi:10.1038/s41568-018-0050-3 |
| 8 | HOLBERT C E, CULLEN M T, CASERO R A JR, et al. Polyamines in cancer: Integrating organismal metabolism and antitumour immunity[J]. Nat Rev Cancer, 2022, 22(8): 467-480. doi:10.1038/s41568-022-00473-2 |
| 9 | TSE R T, WONG C Y, CHIU P K, et al. The Potential Role of Spermine and Its Acetylated Derivative in Human Malignancies[J]. Int J Mol Sci, 2022, 23(3):1258. doi:10.3390/ijms23031258 |
| 10 | PIETROCOLA F, POL J, VACCHELLI E, et al. Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance[J]. Cancer Cell, 2016, 30(1): 147-160. doi:10.1016/j.ccell.2016.05.016 |
| 11 | NIEMI R J, ROINE A N, H?KKINEN M R, et al. Urinary Polyamines as Biomarkers for Ovarian Cancer[J]. Int J Gynecol Cancer, 2017, 27(7): 1360-1366. doi:10.1097/igc.0000000000001031 |
| 12 | TAKAHASHI Y, HORIO H, SAKAGUCHI K, et al. Significant correlation between urinary N1, N12-diacetylspermine and tumor invasiveness in patients with clinical stage IA non-small cell lung cancer[J]. BMC Cancer, 2015, 15(1): 65. doi:10.1186/s12885-015-1068-5 |
| 13 | DURIE B G, SALMON S E, RUSSELL D H. Polyamines as markers of response and disease activity in cancer chemotherapy[J]. Cancer Res, 1977, 37(1): 214-221. |
| 14 | PIRNES-KARHU S, JANTUNEN E, M?NTYMAA P, et al. Spermidine/spermine N1-acetyltransferase activity associates with white blood cell count in myeloid leukemias[J].Exp Hematol, 2014, 42(7): 574-580. doi:10.1016/j.exphem.2014.02.008 |
| 15 | PIRNES-KARHU S, JANTUNEN E, M?NTYMAA P, et al. Spermidine/spermine N(1)-acetyltransferase activity associates with white blood cell count in myeloid leukemias[J]. Exp Hematol, 2014, 42(7): 574-580. doi:10.1016/j.exphem.2014.02.008 |
| 16 | ARBER D A, ORAZI A, HASSERJIAN R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia[J]. Blood, 2016, 127(20): 2391-2405. doi:10.1182/blood-2016-03-643544 |
| 17 | 田祖国,高陆,刘水玉,等. UFC1在弥漫大B细胞淋巴瘤中的表达研究[J]. 实用医学杂志, 2021, 37(3): 324-330. |
| 18 | ROSCHEWSKI M, STAUDT L M, WILSON W H. Diffuse large B-cell lymphoma-treatment approaches in the molecular era[J]. Nat Rev Clin Oncol, 2014, 11(1): 12-23. doi:10.1038/nrclinonc.2013.197 |
| 19 | COIFFIER B, LEPAGE E, BRIERE J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma[J]. N Engl J Med, 2002, 346(4): 235-242. doi:10.1056/nejmoa011795 |
| 20 | MADEO F, EISENBERG T, PIETROCOLA F, et al. Spermidine in health and disease[J]. Science, 2018, 359(6374):eaan2788. doi:10.1126/science.aan2788 |
| 21 | CASTOLDI F, KROEMER G, PIETROCOLA F. Spermidine rejuvenates T lymphocytes and restores anticancer immunosurveillance in aged mice[J]. Oncoimmunology, 2022, 11(1): 2146855. doi:10.1080/2162402x.2022.2146855 |
| 22 | AL-HABSI M, CHAMOTO K, MATSUMOTO K, et al. Spermidine activates mitochondrial trifunctional protein and improves antitumor immunity in mice[J]. Science, 2022, 378(6618): eabj3510. doi:10.1126/science.abj3510 |
| 23 | KAWADA M, SOMENO T, INUMA H, et al. The long-lasting antiproliferative effect of 15-deoxyspergualin through its spermidine moiety[J]. J Antibiot (Tokyo), 2000, 53(7): 705-710. doi:10.7164/antibiotics.53.705 |
| 24 | FORSHELL T P, RIMPI S, NILSSON J A. Chemoprevention of B-cell lymphomas by inhibition of the Myc target spermidine synthase[J]. Cancer Prev Res (Phila), 2010, 3(2): 140-147. doi:10.1158/1940-6207.capr-09-0166 |
| 25 | SMYTH P, SESSLER T, SCOTT C J, et al. FLIP(L): The pseudo-caspase[J]. FEBS J, 2020, 287(19): 4246-4260. doi:10.1111/febs.15260 |
| 26 | 王瑞娟,李超,段丽娟,等. 氯普噻吨调节Akt/mTOR通路对人急性髓系白血病细胞自噬和凋亡的影响[J]. 实用医学杂志, 2023, 39(20): 2584-2590. |
| 27 | GREEN D R, KROEMER G. The pathophysiology of mitochondrial cell death[J]. Science, 2004, 305(5684): 626-629. doi:10.1126/science.1099320 |
| 28 | AL-MANSOORI L, ELSINGA P, GODA S K. Bio-vehicles of cytotoxic drugs for delivery to tumor specific targets for cancer precision therapy[J]. Biomed Pharmacother, 2021, 144: 112260. doi:10.1016/j.biopha.2021.112260 |
/
| 〈 |
|
〉 |