Treatment of novel IL17A inhibitor in glioblastoma implementing 3rd generation co-culture cell line and patient-derived tumor model.
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.
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. Electronic address: jupitex@gmail.com.
Md Shamsuddin Sultan
MSS
Khan
EMAN Research and Testing Laboratory, School of Pharmaceutical Sciences, University of Science Malaysia, Penang, Malaysia.
Muhammad
M
Asif
EMAN Biodiscoveries Sdn Bhd, Eureka Complex, Universiti of Science Malaysia, Minden, Penang, Malaysia.
Mohammed Khadeer Ahamed
MKA
Basheer
Institute for Research in Molecular medicine, University of Science Malaysia, Penang, Malaysia.
Cheng Wei
CW
Kang
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.
Fouad Saleh
FS
Al-Suede
Institute for Research in Molecular medicine, University of Science Malaysia, Penang, Malaysia.
Oon Chern
OC
Ein
Department of Mathematics and Statistics, University of Turku, Finland.
Jing
J
Tang
EMAN Biodiscoveries Sdn Bhd, Eureka Complex, Universiti of Science Malaysia, Minden, Penang, Malaysia; School of Medicine, Department of Pharmacology, Quest International University, Malaysia.
Aman Shah Abdul
ASA
Majid
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. Electronic address: aminmalikshah@gmail.com.
Amin Malik Shah Abdul
AMSA
Majid
D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002109:Caffeic Acids / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D005909:Glioblastoma / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D020381:Interleukin-17 / Q000037:antagonists & inhibitors*; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D002109:Caffeic Acids; D020381:Interleukin-17; C040048:caffeic acid
Caffeic acid derivatives; DBTRG MG; Glioblastoma; IL17A inhibitor; Patient-derived GBM; U87 MG