Antitumor Activity of Curcumin in Glioblastoma

Abstract

Current standard-of-care treatment for glioblastoma, the most common malignant primary central nervous system (CNS) tumor, consists of surgical resection followed by adjuvant chemotherapy and radiation (Stupp protocol), providing an overall median survival of 15 months. With additional treatment using tumor-treating fields (Optune^® therapy, Novocure Ltd., Haifa, Israel), survival can be extended up to 20 months. In spite of significant progress in our understanding of the molecular pathogenesis, the prognosis for patients with malignant gliomas remains poor and additional treatment modalities are critically needed. Curcumin is a bright yellow pigment found in the rhizome of the widely utilized spice, turmeric (Curcuma longa). It has long been used in South Asian traditional medicines and has been demonstrated to have in vitro antioxidant, anti-inflammatory, and antiproliferative effects. Curcumin has been demonstrated to induce multiple cytotoxic effects in tumor cells including cell cycle arrest, apoptosis, autophagy, changes in gene expression, and disruption of molecular signaling. Additionally, curcumin has been shown to potentiate the effect of radiation on cancer cells, while exhibiting a protective effect on normal tissue. Curcumin's positive safety profile and widespread availability make it a promising compound for future clinical trials for high-grade gliomas.

Keywords: anticancer drug; curcumin; glioblastoma; malignant gliomas; nutraceutical; turmeric.

Figure 1

Number of publications since 1988 (sourced from PubMed Database). The blue portion of the bar represents proportion of results returned with search terms “curcumin” and “cancer” while the orange portion represents the total number of studies returned with the search term “curcumin”.

Figure 2

Molecular structure of curcumin and its tautomers. From top to bottom; curcumin in its enol form, curcumin in its keto form, demethoxycurcumin, and bisdemethoxycurcumin.

Figure 3

Summary of well described curcumin pharmacodynamics. Downregulated processes are denoted by blue arrows while upregulated processes are denoted by green arrows.