Abstract:
Glioblastoma multiforme (GBM) is a highly malignant grade IV astrocytoma comprising
54% of all glial cell tumors, with a median survival age of less than 12 months. It is
characterized by cognitive decline, seizures, and development of major depressive disorder
(MDD). Limited treatment options, lower efficacy of drugs to cross the blood brain barrier
(BBB), emerging resistance against the standard treatment drug temozolomide (TMZ), and
aggravation of MDD symptoms by TMZ present the need to develop novel treatment
strategies. This study aimed to investigate the anticancer and antidepressant potential of
silymarin (SIL) in an orthotopic GBM xenograft mouse model. The mouse model was
constructed by injecting U-87 cells into the prefrontal cortex of the brain. Mice were divided
into 8 groups (4 control and 4 GBM induced group), and were treated with normal saline,
Temozolomide (TMZ), Fluoxetine (FLX) standard antidepressant and targeted compound
Silymarin (SIL). Treatment doses were administered intraperitoneally. Six behavioral tests
evaluating behavioral despair, anhedonia, anxiety, depression-like behavior, locomotion,
and social interaction were conducted to evaluate the therapeutic effects of the drugs. TMZ
elevated depression-like behavioral symptoms in both the control and GBM groups in all
six experiments. Silymarin did not induce any depressive symptoms and proved to be
effective in alleviating anxiety- and depression-like behaviors associated with GBM in all
six experiments, showing greater efficacy than the standard antidepressant FLX. Moreover,
Silymarin reduced inflammation in the GBM group. Thus, the efficacy of silymarin merits
further molecular studies, and utilizing silymarin in combinatorial therapy could prove
pivotal in the fight against GBM and other cancers
