(20) A polyphenolic plant flavonoid luteolin potentiates the growth inhibitory effects of erlotinib glioblastoma cell lines.

Objective : The present study investigated the combined effects of erlotinib and luteolin on the proliferation and apoptosis of glioblastoma cell lines overexpressing EGFR or glioma cells expressing truncated EGFR (ΔEGFR). Glioblastomas are the most malignant form of astrocytoma and represent about 50% of all adult primary brain tumors. The multimodal approach to treating glioblastomas includes surgery, radiotherapy, and chemotherapy. However, the prognosis for glioblastomas is very poor because of their invasiveness and chemo- and radio-therapeutic resistance

Methods: We used an MTT assay and trypan blue exclusion to test for cell growth and proliferation. Additionally, we investigated the critical molecular signaling targets perturbed in response to the combined treatment with both erlotinib and luteolin using Western blot analysis. Furthermore, we used Annexin V staining and LDH release to measure the degree of apoptosis in our cell lines

Results: Our results show that the combination of luteolin and erlotinib reduced cell proliferation (p < 0.05) and induced apoptosis by inducing cleavage of PARP and increasing caspase expression. In addition, the combination of luteolin and erlotinib reduced the phosphorylation of downstream EGFR cell signaling targets such as Akt and NF kappa B in a concentration-dependent manner.

Conclusions: These findings suggest that combining luteolin with erlotinib offers a potential treatment strategy for glioblastoma multiforme IV.