The Molecular Mechanisms of Plant-Derived Compounds Targeting Brain Cancer

Abstract

Glioblastoma multiforme (GBM) is one of the most aggressive and malignant forms of brain tumors. Despite recent advances in operative and postoperative treatments, it is almost impossible to perform complete resection of these tumors owing to their invasive and diffuse nature. Several natural plant-derived products, however, have been demonstrated to have promising therapeutic effects, such that they may serve as resources for anticancer drug discovery. The therapeutic effects of one such plant product, n-butylidenephthalide (BP), are wide-ranging in nature, including impacts on cancer cell apoptosis, cell cycle arrest, and cancer cell senescence. The compound also exhibits a relatively high level of penetration through the blood-brain barrier (BBB). Taken together, its actions have been shown to have anti-proliferative, anti-chemoresistance, anti-invasion, anti-migration, and anti-dissemination effects against GBM. In addition, a local drug delivery system for the subcutaneous and intracranial implantation of BP wafers that significantly reduce tumor size in xenograft models, as well as orthotopic and spontaneous brain tumors in animal models, has been developed. Isochaihulactone (ICL), another kind of plant product, possesses a broad spectrum of pharmacological activities, including impacts on cancer cell apoptosis and cell cycle arrest, as well as anti-proliferative and anti-chemoresistance effects. Furthermore, these actions have been specifically shown to have cancer-fighting effects on GBM. In short, the results of various studies reviewed herein have provided substantial evidence indicating that BP and ICH are promising novel anticancer compounds with good potential for clinical applications.

Keywords: O-6-methylguanine-DNA methyltransferase (MGMT); blood-brain barrier (BBB); glioblastoma multiforme (GBM); isochaihulactone (ICL); n-butylidenephthalide (BP); protein kinase C (PKC); retinoblastoma protein (Rb); temozolomide (TMZ).

Figure 1

The cancer-fighting mechanisms of BP. The effects of BP in brain cancer therapy include impacts on cancer cell apoptosis, cell cycle arrest, senescence, and telomerase inactivation. The compound also exhibits a relatively high level of penetration through the blood-brain barrier (BBB). Taken together, these impacts and properties have been shown to be anti-proliferative, anti-drug resistance, anti-invasion, anti-migration, and anti-metastatic. Symbol key: Pathway; Inhibition; Final effect. Please see the content in Section 5.1.

Figure 2

The cancer-fighting mechanisms of ICL. The effects of ICL in cancer therapy include impacts on cancer cell apoptosis, cell cycle arrest, telomerase inactivation, and anti-drug resistance. Symbol key: Pathway; Inhibition; Final effect. Please see the content in Section 5.2.