Cellular and molecular analysis of conditioned medium and quinine-like molecules' effects on GBM cell lines

Glioblastoma multiforme (GBM) is the lethal form of central nervous system cancer with a lack of efficient therapy options. Aggressiveness and invasiveness of the GBM result in poor prognosis and low overall survival. Therefore, the necessity to develop new anti-carcinogenic agents or identify molecules that can expand the therapy options in GBM treatment is still a priority for researchers. Conditioned medium is commonly used in in-vitro studies to simulate tumor microenvironment and has the potential to challenge and expand our current understanding of secretome effect on tumor characteristics. Drug repurposing is an innovative approach based on the use of existing drugs other than their intended purpose contributing to drug development procedures without the time-consuming and high cost of the process. Ion channels are one of the primary regulators of physiological homeostasis with additional critical roles in many essential biological processes related to cancer, such as invasion and metastasis. In this study the effects of conditioned mediums of GBM cell lines on each other was investigated and the anti-carcinogenic effect of a fast sodium channel blocker, hydroquinidine (HQ), was tested on GBM cells. The activity of HQ on GBM cells or the effects on conditioned mediums on each other was evaluated using widely applied cell culture and molecular biology techniques. Conditioned medium harvested from U87 or LN229 cells at 48th h time point exhibited an anti-growth activity on each other by altering the gene expression pattern. Furthermore, the conditioned medium of LN229 decreased the migration capacity of U87 cells, and the conditioned medium of U87 cells significantly suppressed the LN229 proliferation. A significant anti-carcinogenic effect of HQ on temozolomide (TMZ)-sensitive and -resistant GBM cells was observed through the increased apoptosis and decreased proliferation which are due to the altered gene expression profile related to cell-cycle and cell death.