Pine (Pinus morrisonicola Hayata) Needle Extracts Sensitize GBM8901 Human Glioblastoma Cells to Temozolomide by Downregulating Autophagy and O⁶-Methylguanine-DNA Methyltransferase Expression

Abstract

Pine needle extracts of Pinus morrisonicola (Hayata) are commonly used as a functional health beverage. However, it remains unclear what the mechanism is underlying the antitumor activity of pine needle extract. The aims of present study were to investigate the anti-glioblastoma effects of pine needle extracts as well as its bioactive compounds. From three different solvent extracts of pine needles, the water extract displayed the strongest cytotoxicity effects on GBM8901 glioblastoma cells. The isolated compounds were identified as pinocembrin, chrysin, and tiliroside. Chrysin was the most active ingredient of pine needle extract for the induction of apoptosis and suppression of migration and invasion. It also markedly inhibited temozolomide (TMZ)-induced autophagy and O(6)-methylguanine-DNA methyltransferase (MGMT) expression. Because both autophagy and MGMT overexpression have been implicated to TMZ-induced drug resistance in glioblastoma, our results showed that pine needle extract and chrysin may serve as a potential anticancer agent against glioblastoma, especially with regard to sensitizing glioblastoma cells resistant to TMZ.

Chrysin Protects Rat Kidney from Paracetamol-Induced Oxidative Stress, Inflammation, Apoptosis, and Autophagy: A Multi-Biomarker Approach

“…However, Figure 5 shows that LC3B levels were reduced in the groups given CR treatments. In a similar study, it was reported that CR protected glioblastoma cells against treatment with chronic temozolomide and inhibited temozolomide-induced autophagia [62]. …”

Targeting autophagy to sensitive glioma to temozolomide treatment

“… Chrysin inhibited TMZ-induced autophagy and MGMT expression. [ 75 ] Chrysin 20 μM/24 hours Human U87, GBM8401 and GBM-SKH cells TMZ 400 μM/72 hours Resveratrol enhanced the therapeutic effect of TMZ against malignant glioma. Coadministration of resveratrol and TMZ reduced tumor volumes by suppressing ROS/ERK-mediated autophagy.…”

“…In this regard, natural products, such as flavonoids, have received considerable attention because of their lower amount of side effects and effectively inhibition of autophagy-mediated the pro-survival roles [ 74 ]. Chrysin, the most active ingredient of pine needle extract, markedly inhibited TMZ-induced autophagy and induced apoptosis, indicating that chrysin may serve as a potential anticancer agent against glioblastomas [ 75 ]. Resveratrol (Rsv), a natural, purified polyphenolic compound, has additive toxicity with TMZ in several glioma cell lines in vitro [ 76 ] and in vivo [ 42 ].…”

Characterization of Vasorelaxant Principles from the Needles of Pinus morrisonicola Hayata

“…It is believed to have many pharmacological effects, such as anti-aging, anti-hypercholesterolemia and anti-hypertension. It was reported that the water extract of 5LP inhibits proliferation and promotes apoptosis of human promyelocytic leukemia cells and exhibited strong cytotoxic effects on GBM8901 glioblastoma cells [ 3 , 4 ]. Moreover, the ethyl acetate fraction and the ethanol extract of pine needles were found to contain large amounts of polyphenols and flavonoids, and have been shown to possess strong free radical scavenging ability [ 5 ].…”