Specific compositions of cannabis sativa compounds have cytotoxic activity and inhibit motility and colony formation of human glioblastoma cells in vitro

Hadar Peeri, Nurit Shalev, Ajjampura C. Vinayaka, Rephael Nizar, Gila Kazimirsky, Dvora Namdar, Seegehalli M. Anil, Eduard Belausov, Chaya Brodie, Hinanit Koltai

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Glioblastoma multiforme (GBM) is the most lethal subtype of glioma. Cannabis sativa is used for the treatment of various medical conditions. Around 150 phytocannabinoids have been identified in C. sativa, among them Δ‐9‐tetrahydrocannabinol (THC) and cannabidiol (CBD) that trigger GBM cell death. However, the optimal combinations of cannabis molecules for anti‐GBM activity are unknown. Chemical composition was determined using high‐performance liquid chro-matography (HPLC) and gas chromatography mass spectrometry (GC/MS). Cytotoxic activity was determined by XTT and lactate dehydrogenase (LDH) assays and apoptosis and cell cycle by fluo-rescence‐activated cell sorting (FACS). F‐actin structures were observed by confocal microscopy, gene expression by quantitative PCR, and cell migration and invasion by scratch and transwell as-says, respectively. Fractions of a high‐THC cannabis strain extract had significant cytotoxic activity against GBM cell lines and glioma stem cells derived from tumor specimens. A standard mix (SM) of the active fractions F4 and F5 induced apoptosis and expression of endoplasmic reticulum (ER)‐ stress associated‐genes. F4 and F5 inhibited cell migration and invasion, altered cell cytoskeletons, and inhibited colony formation in 2 and 3‐dimensional models. Combinations of cannabis compounds exert cytotoxic, anti‐proliferative, and anti‐migratory effects and should be examined for efficacy on GBM in pre‐clinical studies and clinical trials.

Original languageEnglish
Article number1720
JournalCancers
Volume13
Issue number7
DOIs
StatePublished - 5 Apr 2021

Bibliographical note

Publisher Copyright:
© 2021 by the author. Licensee MDPI, Basel, Switzerland.

Keywords

  • Apoptosis
  • Cannabis
  • Cell cycle
  • Cell migration
  • Cytotoxicity
  • Endoplasmic reticulum stress
  • F‐actin
  • Glioblastoma
  • Glioma stem cells
  • Neurospheres
  • Phytocannabinoids

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