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Treatment of novel IL17A inhibitor in glioblastoma implementing 3rd generation co-culture cell line and patient-derived tumor model.

Author information

Affiliations

  • 1. EMAN Research and Testing Laboratory, School of Pharmaceutical Sciences, University of Science Malaysia, Penang, Malaysia; EMAN Biodiscoveries Sdn Bhd, Eureka Complex, Universiti of Science Malaysia, Minden, Penang, Malaysia; Eman research, Level 3, 81 Flushcombe Rd, Blacktown, NSW 2148, Australia.
      Authors
    • Khan MSS 1
    (1 author)
  • 2. EMAN Research and Testing Laboratory, School of Pharmaceutical Sciences, University of Science Malaysia, Penang, Malaysia.
      Authors
    • Asif M 2
    (1 author)
  • 3. EMAN Biodiscoveries Sdn Bhd, Eureka Complex, Universiti of Science Malaysia, Minden, Penang, Malaysia.
      Authors
    • Basheer MKA 3
    (1 author)
  • 4. Institute for Research in Molecular medicine, University of Science Malaysia, Penang, Malaysia.
      Authors
    • Kang CW 4
    • Ein OC 4
    (2 authors)
  • 5. EMAN Research and Testing Laboratory, School of Pharmaceutical Sciences, University of Science Malaysia, Penang, Malaysia; EMAN Biodiscoveries Sdn Bhd, Eureka Complex, Universiti of Science Malaysia, Minden, Penang, Malaysia.
      Authors
    • Al-Suede FS 5
    • Majid AMSA 5
    (2 authors)
    • Show all (7)

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European Journal of Pharmacology, 18 Mar 2017, 803:24-38
https://doi.org/10.1016/j.ejphar.2017.03.031 PMID: 28322833 

Abstract 

Despite many treatment options, cancer remains a growing problem and has become the second leading cause of death globally. Here, we present fluorescence molecular tomography (FMT) data regarding the reversion of third generation co-cultured U87+DBTRG and patient-derived GBM tumor model after treatment with novel IL17A inhibitor named FLVM and FLVZ (organic derivatives of caffeic acid). FMT was used to determine tumor angiogenesis volume (assessment of number of blood vessel; the expression of angiogenic factors CD34 and other angiogenic cancer bio-markers) in U87+DBTRG and patient-derived gliomas. Immunohistochemistry was used to determine microvessel density [CD34], and cell proliferation [Ki67]. Western blot was used to assess the interleukin 17A [IL17A], vascular endothelial growth factor [VEGF] and hypoxia-inducible factor-1α [HIF-1α]. Antibody array was used to assess the cancer bio-markers in co-cultured U87+DBTRG gliomas. Animal survival was found to be significantly increased (P<0.0001) after FLVM treatment compared with control-IL17A. After FMT detection, FLVM, administered orally, was found to decrease tumor growth (P<0.0001). FLVM and FLVZ administration resulted in significant decreases in tumor hypoxia [HIF-1α (P<0.05)], angiogenesis [CD34 (P<0.05)], VEGF, IL17A and cell proliferation [Ki67 (P<0.05)] and caused a significant increase of Bax, caspase and FasL (P<0.05), compared with untreated animals. Additionally, Leptin, LPL (P<0.01), FFA (P<0.05) and adipogenesis were downregulated and no additive toxicity was found in mice except calorie-restriction like effect. Use of FLVM can be considered as a novel inhibitor of IL17A for the treatment of human gliomas.

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Read article at publisher's site: https://doi.org/10.1016/j.ejphar.2017.03.031

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