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Article Open Access

Clarifying the molecular mechanism of tomentosin‑induced antiproliferative and proapoptotic effects in human multiple myeloma via gene expression profile and genetic interaction network analysis

  • Authors:
    • Patrizia Virdis
    • Rossana Migheli
    • Valentina Bordoni
    • Francesco Paolo Fiorentino
    • Luca Sanna
    • Irene Marchesi
    • Giorgio Pintore
    • Grazia Galleri
    • Maria Rosaria Muroni
    • Luigi Bagella
    • Claudio Fozza
    • Maria Rosaria De Miglio
    • Luigi Podda
  • View Affiliations / Copyright

    Affiliations: Department of Medical, Surgical and Experimental Sciences, University of Sassari, I‑07100 Sassari, Sardinia, Italy, Department of Biomedical Sciences, University of Sassari, I‑07100 Sassari, Sardinia, Italy, Kitos Biotech Srls, Porto Conte Ricerche, I‑07100 Sassari, Sardinia, Italy, Department of Chemistry and Pharmacy, University of Sassari, I‑07100 Sassari, Sardinia, Italy
    Copyright: © Virdis et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 213
    |
    Published online on: October 11, 2021
       https://doi.org/10.3892/ijmm.2021.5046
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Abstract

Multiple myeloma (MM) is an aggressive B cell malignancy. Substantial progress has been made in the therapeutic context for patients with MM, however it still represents an incurable disease due to drug resistance and recurrence. Development of more effective or synergistic therapeutic approaches undoubtedly represents an unmet clinical need. Tomentosin is a bioactive natural sesquiterpene lactone extracted by various plants with therapeutic properties, including anti‑neoplastic effects. In the present study, the potential antitumor activity of tomentosin was evaluated on the human RPMI‑8226 cell line, treated with increasing tomentosin concentration for cytotoxicity screening. The data suggested that both cell cycle arrest and cell apoptosis could explain the antiproliferative effects of tomentosin and may result in the inhibition of RPMI‑8226 cell viability. To assess differentially expressed genes contributing to tomentosin activity and identify its mechanism of action, a microarray gene expression profile was performed, identifying 126 genes deregulated by tomentosin. To address the systems biology and identify how tomentosin deregulates gene expression in MM from a systems perspective, all deregulated genes were submitted to enrichment and molecular network analysis. The Protein‑Protein Interaction (PPI) network analysis showed that tomentosin in human MM induced the downregulation of genes involved in several pathways known to lead immune‑system processes, such as cytokine‑cytokine receptor interaction, chemokine or NF‑κB signaling pathway, as well as genes involved in pathways playing a central role in cellular neoplastic processes, such as growth, proliferation, migration, invasion and apoptosis. Tomentosin also induced endoplasmic reticulum stress via upregulation of cyclic AMP‑dependent transcription factor ATF‑4 and DNA damage‑inducible transcript 3 protein genes, suggesting that in the presence of tomentosin the protective unfolded protein response signaling may induce cell apoptosis. The functional connections analysis executed using the Connectivity Map tool, suggested that the effects of tomentosin on RPMI‑8226 cells might be similar to those exerted by heat shock proteins inhibitors. Taken together, these data suggested that tomentosin may be a potential drug candidate for the treatment of MM.
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View References

1 

Kumar SK, Dispenzieri A, Lacy MQ, Gertz MA, Buadi FK, Pandey S, Kapoor P, Dingli D, Hayman SR, Leung N, et al: Continued improvement in survival in multiple myeloma: Changes in early mortality and outcomes in older patients. Leukemia. 28:1122–1128. 2014. View Article : Google Scholar :

2 

Röllig C, Knop S and Bornhäuser M: Multiple myeloma. Lancet. 385:2197–2208. 2015. View Article : Google Scholar

3 

van de Donk NWCJ, Pawlyn C and Yong KL: Multiple myeloma. Lancet. 397:410–427. 2021. View Article : Google Scholar : PubMed/NCBI

4 

Kyle RA and Rajkumar SV: Drug therapy: Multiple myeloma. N Engl J Med. 351:1860–1873. 2004. View Article : Google Scholar : PubMed/NCBI

5 

Roodman GD: Pathogenesis of myeloma bone disease. Leukemia. 23:435–441. 2009. View Article : Google Scholar

6 

Raje NS, Bhatta S and Terpos E: Role of the RANK/RANKL pathway in multiple myeloma. Clin Cancer Res. 25:12–20. 2019. View Article : Google Scholar

7 

Kyle RA, Child JA, Anderson K, Barlogie B, Bataille R, Bensinger W, Bladé J, Boccadoro M, Dalton W, Dimopoulos M, et al: Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: A report of the international myeloma working group. Br J Haematol. 121:749–757. 2003. View Article : Google Scholar

8 

Maiese EM, Evans KA, Chu BC and Irwin DE: Temporal trends in survival and healthcare costs in patients with multiple myeloma in the United States. Am Heal Drug Benefits. 11:39–46. 2018.

9 

Fonseca R, Abouzaid S, Bonafede M, Cai Q, Parikh K, Cosler L and Richardson P: Trends in overall survival and costs of multiple myeloma, 2000-2014. Leukemia. 31:1915–1921. 2017. View Article : Google Scholar :

10 

Durie BGM, Hoering A, Abidi MH, Rajkumar SV, Epstein J, Kahanic SP, Thakuri M, Reu F, Reynolds CM, Sexton R, et al: Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): A randomised, open-label, phase 3 trial. Lancet. 389:519–527. 2017. View Article : Google Scholar :

11 

Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins K, Brown J, Drayson MT and Selby PJ; Medical Research Council Adult Leukaemia Working Party: High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med. 348:1875–1883. 2003. View Article : Google Scholar : PubMed/NCBI

12 

McCarthy PL, Holstein SA, Petrucci MT, Richardson PG, Hulin C, Tosi P, Bringhen S, Musto P, Anderson KC, Caillot D, et al: Lenalidomide maintenance after autologous stem-cell transplantation in newly diagnosed multiple myeloma: A meta-analysis. J Clin Oncol. 35:3279–3289. 2017. View Article : Google Scholar : PubMed/NCBI

13 

Bergsagel PL: Where we were, where we are, where we are going: Progress in multiple myeloma. Am Soc Clin Oncol Educ Book:. 199:–203. 2014.

14 

Teoh PJ and Chng WJ: CAR T-cell therapy in multiple myeloma: More room for improvement. Blood Cancer J. 11:842021. View Article : Google Scholar : PubMed/NCBI

15 

Ludwig H, Delforge M, Facon T, Einsele H, Gay F, Moreau P, Avet-Loiseau H, Boccadoro M, Hajek R, Mohty M, et al: Prevention and management of adverse events of novel agents in multiple myeloma: A consensus of the European myeloma network. Leukemia. 32:1542–1560. 2018. View Article : Google Scholar : PubMed/NCBI

16 

Pulte D, Redaniel MT, Brenner H, Jansen L and Jeffreys M: Recent improvement in survival of patients with multiple myeloma: Variation by ethnicity. Leuk Lymphoma. 55:1083–1089. 2014. View Article : Google Scholar

17 

Kristinsson SY, Anderson WF and Landgren O: Improved long-term survival in multiple myeloma up to the age of 80 years. Leukemia. 28:1346–1348. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Giuliani N, Accardi F, Marchica V, Dalla Palma B, Storti P, Toscani D, Vicario E and Malavasi F: Novel targets for the treatment of relapsing multiple myeloma. Expert Rev Hematol. 12:481–496. 2019. View Article : Google Scholar : PubMed/NCBI

19 

Virdis P, Migheli R, Galleri G, Fancello S, Cadoni MPL, Pintore G, Petretto GL, Marchesi I, Fiorentino FP, di Francesco A, et al: Antiproliferative and proapoptotic effects of Inula viscosa extract on Burkitt lymphoma cell line. Tumor Biol. 42:10104283199010612020. View Article : Google Scholar

20 

Barbetti P, Chiappini I, Fardella G and Menghini A: A new eudesmane acid from Dittrichia (Inula) viscosa. Planta Med. 51:4711985. View Article : Google Scholar : PubMed/NCBI

21 

Lauro L and Rolih C: Observations and research on an extract of Inula viscosa Ait. Boll Soc Ital Biol Sper. 66:829–834. 1990.In Italian. PubMed/NCBI

22 

Lev E and Amar Z: Ethnopharmacological survey of traditional drugs sold in Israel at the end of the 20th century. J Ethnopharmacol. 72:191–205. 2000. View Article : Google Scholar : PubMed/NCBI

23 

Yaniv Z, Dafni A, Friedman J and Palevitch D: Plants used for the treatment of diabetes in Israel. J Ethnopharmacol. 19:145–151. 1987. View Article : Google Scholar : PubMed/NCBI

24 

Al-Qura'n S: Ethnopharmacological survey of wild medicinal plants in Showbak, Jordan. J Ethnopharmacol. 123:45–50. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Messaoudi M, Chahmi N, El-Mzibri M, Gmouh S, Amzazi S, Benbacer L and El-Hassouni M: Cytotoxic Effect and chemical composition of Inula viscosa from three different regions of morocco. Eur J Med Plants. 16:1–9. 2016. View Article : Google Scholar

26 

Rozenblat S, Grossman S, Bergman M, Gottlieb H, Cohen Y and Dovrat S: Induction of G2/M arrest and apoptosis by sesquiterpene lactones in human melanoma cell lines. Biochem Pharmacol. 75:369–382. 2008. View Article : Google Scholar

27 

Yang H, Zhao H, Dong X, Yang Z and Chang W: Tomentosin induces apoptotic pathway by blocking inflammatory mediators via modulation of cell proteins in AGS gastric cancer cell line. J Biochem Mol Toxicol. 34:e225012020. View Article : Google Scholar : PubMed/NCBI

28 

Merghoub N, El Btaouri H, Benbacer L, Gmouh S, Trentesaux C, Brassart B, Attaleb M, Madoulet C, Wenner T, Amzazi S, et al: Tomentosin induces telomere shortening and caspase-dependant apoptosis in cervical cancer cells. J Cell Biochem. 118:1689–1698. 2017. View Article : Google Scholar

29 

Lee CM, Lee J, Nam MJ, Choi YS and Park SH: Tomentosin displays anti-carcinogenic effect in human osteosarcoma MG-63 cells via the induction of intracellular reactive oxygen species. Int J Mol Sci. 20:15082019. View Article : Google Scholar :

30 

Ihaka R and Gentleman R: R: A language for data analysis and graphics. J Comput Graph Stat. 5:299–314. 1996.

31 

Ellis B, Gentleman R, Hahne F, Le Meur N, Sarkar D and Jiang M: flowViz: Visualization for flow cytometry. R package version 1.56.0. 2021, https://www.bioconductor.org/packages/release/bioc/html/flowViz.html.

32 

Love MI, Huber W and Anders S: Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15:5502014. View Article : Google Scholar : PubMed/NCBI

33 

Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES and Mesirov JP: Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 102:15545–15550. 2005. View Article : Google Scholar : PubMed/NCBI

34 

Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, et al: Gene ontology: Tool for the unification of biology. The gene ontology consortium Nat Genet. 25:25–29. 2000.

35 

Carbon S, Douglass E, Good BM, Unni DR, Harris NL, Mungall CJ, Basu S and Elser J: The gene ontology resource: Enriching a GOld mine. Nucleic Acids Res. 49D:D325–D334. 2021.

36 

Kanehisa M and Goto S: KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28:27–30. 2000. View Article : Google Scholar

37 

Igney FH and Krammer PH: Death and anti-death: Tumour resistance to apoptosis. Nat Rev Cancer. 2:277–288. 2002. View Article : Google Scholar : PubMed/NCBI

38 

Costa LJ, Brill IK, Omel J, Godby K, Kumar SK and Brown EE: Recent trends in multiple myeloma incidence and survival by age, race, and ethnicity in the United States. Blood Adv. 1:282–287. 2017. View Article : Google Scholar

39 

Cavo M, Tacchetti P, Patriarca F, Petrucci MT, Pantani L, Galli M, Di Raimondo F, Crippa C, Zamagni E, Palumbo A, et al: Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: A randomised 3 study. Lancet. 376:2075–2085. 2010. View Article : Google Scholar : PubMed/NCBI

40 

Miguel JS, Weisel K, Moreau P, Lacy M, Song K, Delforge M, Karlin L, Goldschmidt H, Banos A, Oriol A, et al: Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): A randomised, open-label, phase 3 trial. Lancet Oncol. 14:1055–1066. 2013. View Article : Google Scholar : PubMed/NCBI

41 

Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P, Munshi N, Anaissie E, Wilson C, Dhodapkar M, et al: Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med. 341:1565–1571. 1999. View Article : Google Scholar : PubMed/NCBI

42 

Palumbo A, Hajek R, Delforge M, Kropff M, Petrucci MT, Catalano J, Gisslinger H, Wiktor-Jędrzejczak W, Zodelava M, Weisel K, et al: Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med. 366:1759–1769. 2012. View Article : Google Scholar : PubMed/NCBI

43 

Dimopoulos M, Spencer A, Attal M, Prince HM, Harousseau JL, Dmoszynska A, San Miguel J, Hellmann A, Facon T, Foà R, et al: Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 357:2123–2132. 2007. View Article : Google Scholar : PubMed/NCBI

44 

Drexler HG and MacLeod RAF: Malignant hematopoietic cell lines: In vitro models for the study of plasmacytoid dendritic cell leukemia. Leuk Res. 33:1166–1169. 2009. View Article : Google Scholar : PubMed/NCBI

45 

Yang L, Xie J, Almoallim HS, Alharbi SA and Chen Y: Tomentosin inhibits cell proliferation and induces apoptosis in MOLT-4 leukemia cancer cells through the inhibition of mTOR/PI3K/Akt signaling pathway. J Biochem Mol Toxicol. 35:e227192021. View Article : Google Scholar : PubMed/NCBI

46 

El Yaagoubi OM, Lahmadi A, Bouyahya A, Filali H, Samaki H, El Antri S and Aboudkhil S: Antitumor effect of Inula viscosa extracts on DMBA-induced skin carcinoma are mediated by proteasome inhibition. Biomed Res Int. 2021:66875892021. View Article : Google Scholar :

47 

Zeissig MN, Hewett DR, Panagopoulos V, Mrozik KM, To LB, Croucher PI, Zannettino ACW and Vandyke K: Expression of the chemokine receptor CCR1 promotes the dissemination of multiple myeloma plasma cells in vivo. Haematologica. Nov 5–2020.Epub ahead of print. View Article : Google Scholar

48 

Dairaghi DJ, Oyajobi BO, Gupta A, McCluskey B, Miao S, Powers JP, Seitz LC, Wang Y, Zeng Y, Zhang P, et al: CCR1 blockade reduces tumor burden and osteolysis in vivo in a mouse model of myeloma bone disease. Blood. 120:1449–1457. 2012. View Article : Google Scholar : PubMed/NCBI

49 

Ganghammer S, Gutjahr J, Hutterer E, Krenn PW, Pucher S, Zelle-Rieser C, Jöhrer K, Wijtmans M, Leurs R, Smit MJ, et al: Combined CXCR3/CXCR4 measurements are of high prognostic value in chronic lymphocytic leukemia due to negative co-operativity of the receptors. Haematologica. 101:e99–e102. 2016. View Article : Google Scholar :

50 

Mulligan AM, Raitman I, Feeley L, Pinnaduwage D, Nguyen LT, O'Malley FP, Ohashi PS and Andrulis IL: Tumoral lymphocytic infiltration and expression of the chemokine CXCL10 in breast cancers from the ontario familial breast cancer registry. Clin Cancer Res. 19:336–346. 2013. View Article : Google Scholar :

51 

Bolomsky A, Schreder M, Hübl W, Zojer N, Hilbe W and Ludwig H: Monokine induced by interferon gamma (MIG/CXCL9) is an independent prognostic factor in newly diagnosed myeloma. Leuk Lymphoma. 57:2516–2525. 2016. View Article : Google Scholar : PubMed/NCBI

52 

Guillerey C, Huntington ND and Smyth MJ: Targeting natural killer cells in cancer immunotherapy. Nat Immunol. 17:1025–1036. 2016. View Article : Google Scholar : PubMed/NCBI

53 

Bonanni V, Antonangeli F, Santoni A and Bernardini G: Targeting of CXCR3 improves anti-myeloma efficacy of adoptively transferred activated natural killer cells. J Immunother Cancer. 7:2902019. View Article : Google Scholar : PubMed/NCBI

54 

Vijay K: Toll-like receptors in immunity and inflammatory diseases: Past, present, and future. Int Immunopharmacol. 59:391–412. 2018. View Article : Google Scholar : PubMed/NCBI

55 

Chiron D, Bekeredjian-Ding I, Pellat-Deceunynck C, Bataille R and Jego G: Toll-like receptors: Lessons to learn from normal and malignant human B cells. Blood. 112:2205–2213. 2008. View Article : Google Scholar : PubMed/NCBI

56 

Xu Y, Zhao Y, Huang H, Chen G, Wu X, Wang Y, Chang W, Zhu Z, Feng Y and Wu D: Expression and function of toll-like receptors in multiple myeloma patients: Toll-like receptor ligands promote multiple myeloma cell growth and survival via activation of nuclear factor-kappaB. Br J Haematol. 150:543–553. 2010. View Article : Google Scholar : PubMed/NCBI

57 

Rossi D: Role of MYD88 in lymphoplasmacytic lymphoma diagnosis and pathogenesis. Hematology Am Soc Hematol Educ Program. 2014:113–118. 2014. View Article : Google Scholar

58 

de Boussac H, Bruyer A, Jourdan M, Maes A, Robert N, Gourzones C, Vincent L, Seckinger A, Cartron G, Hose D, et al: Kinome expression profiling to target new therapeutic avenues in multiple myeloma. Haematologica. 105:784–795. 2020. View Article : Google Scholar :

59 

Crawley JB, Williams LM, Mander T, Brennan FM and Foxwell BMJ: Interleukin-10 stimulation of phosphatidylinositol 3-kinase and p70 S6 kinase is required for the proliferative but not the antiinflammatory effects of the cytokine. J Biol Chem. 271:16357–16362. 1996. View Article : Google Scholar : PubMed/NCBI

60 

Zhou JH, Broussard SR, Strle K, Freund GG, Johnson RW, Dantzer R and Kelley KW: IL-10 inhibits apoptosis of promyeloid cells by activating insulin receptor substrate-2 and phosphatidylinositol 3′-kinase. J Immunol. 167:4436–4442. 2001. View Article : Google Scholar : PubMed/NCBI

61 

Zhan F, Huang Y, Colla S, Stewart JP, Hanamura I, Gupta S, Epstein J, Yaccoby S, Sawyer J, Burington B, et al: The molecular classification of multiple myeloma. Blood. 108:2020–2028. 2006. View Article : Google Scholar : PubMed/NCBI

62 

Zhang PP, Wang YC, Cheng C, Zhang F, Ding DZ and Chen DK: Runt-related transcription factor 2 influences cell adhesion-mediated drug resistance and cell proliferation in B-cell non-Hodgkin's lymphoma and multiple myeloma. Leuk Res. 92:106340Mar 9–2020. View Article : Google Scholar : PubMed/NCBI

63 

Luo JH: Oncogenic activity of MCM7 transforming cluster. World J Clin Oncol. 2:120–124. 2011. View Article : Google Scholar : PubMed/NCBI

64 

Cortez D, Glick G and Elledge SJ: Minichromosome maintenance proteins are direct targets of the ATM and ATR checkpoint kinases. Proc Natl Acad Sci USA. 101:10078–10083. 2004. View Article : Google Scholar : PubMed/NCBI

65 

Tsao CC, Geisen C and Abraham RT: Interaction between human MCM7 and Rad17 proteins is required for replication checkpoint signaling. EMBO J. 23:4660–4669. 2004. View Article : Google Scholar : PubMed/NCBI

66 

Tian L, Liu J, Xia GH and Chen BA: RNAi-mediated knockdown of MCM7 gene on CML cells and its therapeutic potential for leukemia. Med Oncol. 34:212017. View Article : Google Scholar : PubMed/NCBI

67 

Moll UM and Petrenko O: The MDM2-p53 interaction. Mol Cancer Res. 1:1001–1008. 2003.

68 

Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, Kong N, Kammlott U, Lukacs C, Klein C, et al: In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science. 303:844–848. 2004. View Article : Google Scholar : PubMed/NCBI

69 

Teoh PJ, Chung TH, Sebastian S, Choo SN, Yan J, Ng SB, Fonseca R and Chng WJ: P53 haploinsufficiency and functional abnormalities in multiple myeloma. Leukemia. 28:2066–2074. 2014. View Article : Google Scholar : PubMed/NCBI

70 

Saha MN, Qiu L and Chang H: Targeting p53 by small molecules in hematological malignancies. J Hematol Oncol. 6:232013. View Article : Google Scholar : PubMed/NCBI

71 

Teoh PJ and Chng WJ: P53 abnormalities and potential therapeutic targeting in multiple myeloma. Biomed Res Int. 2014:7179192014. View Article : Google Scholar : PubMed/NCBI

72 

Halder SK, Beauchamp RD and Datta PK: Smad7 induces tumorigenicity by blocking TGF-beta-induced growth inhibition and apoptosis. Exp Cell Res. 307:231–246. 2005. View Article : Google Scholar : PubMed/NCBI

73 

Chen R, Wierda WG, Chubb S, Hawtin RE, Fox JA, Keating MJ, Gandhi V and Plunkett W: Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. Blood. 113:4637–4645. 2009. View Article : Google Scholar : PubMed/NCBI

74 

Czudor Z, Balogh M, Bánhegyi P, Boros S, Breza N, Dobos J, Fábián M, Horváth Z, Illyés E, Markó P, et al: Novel compounds with potent CDK9 inhibitory activity for the treatment of myeloma. Bioorganic Med Chem Lett. 28:769–773. 2018. View Article : Google Scholar

75 

Hartl FU: Molecular chaperones in cellular protein folding. Nature. 381:571–580. 1996. View Article : Google Scholar : PubMed/NCBI

76 

Muralidharan S and Mandrekar P: Cellular stress response and innate immune signaling: Integrating pathways in host defense and inflammation. J Leukoc Biol. 94:1167–1184. 2013. View Article : Google Scholar : PubMed/NCBI

77 

Chatterjee M, Andrulis M, Stühmer T, Müller E, Hofmann C, Steinbrunn T, Heimberger T, Schraud H, Kressmann S, Einsele H and Bargou RC: The PI3K/Akt signaling pathway regulates the expression of Hsp70, which critically contributes to Hsp90-chaperone function and tumor cell survival in multiple myeloma. Haematologica. 98:1132–1141. 2013. View Article : Google Scholar :

78 

Zhang L, Fok JJL, Mirabella F, Aronson LI, Fryer RA, Workman P, Morgan GJ and Davies FE: Hsp70 inhibition induces myeloma cell death via the intracellular accumulation of immunoglobulin and the generation of proteotoxic stress. Cancer Lett. 339:49–59. 2013. View Article : Google Scholar : PubMed/NCBI

79 

Braunstein MJ, Scott SS, Scott CM, Behrman S, Walter P, Wipf P, Coplan JD, Chrico W, Joseph D, Brodsky JL and Batuman O: Antimyeloma effects of the heat shock protein 70 molecular chaperone inhibitor MAL3-101. J Oncol. 2011:2320372011. View Article : Google Scholar : PubMed/NCBI

80 

Workman P and Davies FE: A stressful life (or death): Combinatorial proteotoxic approaches to cancer-selective therapeutic vulnerability. Oncotarget. 2:277–280. 2011. View Article : Google Scholar : PubMed/NCBI

81 

Tiku V, Tan MW and Dikic I: Mitochondrial functions in infection and immunity: (Trends in Cell Biology 30, 263-275, 2020). Trends Cell Biol. 30:7482020. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Virdis P, Migheli R, Bordoni V, Fiorentino FP, Sanna L, Marchesi I, Pintore G, Galleri G, Muroni MR, Bagella L, Bagella L, et al: Clarifying the molecular mechanism of tomentosin‑induced antiproliferative and proapoptotic effects in human multiple myeloma via gene expression profile and genetic interaction network analysis. Int J Mol Med 48: 213, 2021.
APA
Virdis, P., Migheli, R., Bordoni, V., Fiorentino, F.P., Sanna, L., Marchesi, I. ... Podda, L. (2021). Clarifying the molecular mechanism of tomentosin‑induced antiproliferative and proapoptotic effects in human multiple myeloma via gene expression profile and genetic interaction network analysis. International Journal of Molecular Medicine, 48, 213. https://doi.org/10.3892/ijmm.2021.5046
MLA
Virdis, P., Migheli, R., Bordoni, V., Fiorentino, F. P., Sanna, L., Marchesi, I., Pintore, G., Galleri, G., Muroni, M. R., Bagella, L., Fozza, C., De Miglio, M. R., Podda, L."Clarifying the molecular mechanism of tomentosin‑induced antiproliferative and proapoptotic effects in human multiple myeloma via gene expression profile and genetic interaction network analysis". International Journal of Molecular Medicine 48.6 (2021): 213.
Chicago
Virdis, P., Migheli, R., Bordoni, V., Fiorentino, F. P., Sanna, L., Marchesi, I., Pintore, G., Galleri, G., Muroni, M. R., Bagella, L., Fozza, C., De Miglio, M. R., Podda, L."Clarifying the molecular mechanism of tomentosin‑induced antiproliferative and proapoptotic effects in human multiple myeloma via gene expression profile and genetic interaction network analysis". International Journal of Molecular Medicine 48, no. 6 (2021): 213. https://doi.org/10.3892/ijmm.2021.5046
Copy and paste a formatted citation
x
Spandidos Publications style
Virdis P, Migheli R, Bordoni V, Fiorentino FP, Sanna L, Marchesi I, Pintore G, Galleri G, Muroni MR, Bagella L, Bagella L, et al: Clarifying the molecular mechanism of tomentosin‑induced antiproliferative and proapoptotic effects in human multiple myeloma via gene expression profile and genetic interaction network analysis. Int J Mol Med 48: 213, 2021.
APA
Virdis, P., Migheli, R., Bordoni, V., Fiorentino, F.P., Sanna, L., Marchesi, I. ... Podda, L. (2021). Clarifying the molecular mechanism of tomentosin‑induced antiproliferative and proapoptotic effects in human multiple myeloma via gene expression profile and genetic interaction network analysis. International Journal of Molecular Medicine, 48, 213. https://doi.org/10.3892/ijmm.2021.5046
MLA
Virdis, P., Migheli, R., Bordoni, V., Fiorentino, F. P., Sanna, L., Marchesi, I., Pintore, G., Galleri, G., Muroni, M. R., Bagella, L., Fozza, C., De Miglio, M. R., Podda, L."Clarifying the molecular mechanism of tomentosin‑induced antiproliferative and proapoptotic effects in human multiple myeloma via gene expression profile and genetic interaction network analysis". International Journal of Molecular Medicine 48.6 (2021): 213.
Chicago
Virdis, P., Migheli, R., Bordoni, V., Fiorentino, F. P., Sanna, L., Marchesi, I., Pintore, G., Galleri, G., Muroni, M. R., Bagella, L., Fozza, C., De Miglio, M. R., Podda, L."Clarifying the molecular mechanism of tomentosin‑induced antiproliferative and proapoptotic effects in human multiple myeloma via gene expression profile and genetic interaction network analysis". International Journal of Molecular Medicine 48, no. 6 (2021): 213. https://doi.org/10.3892/ijmm.2021.5046
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