A Review of Curcumin and Its Derivatives as Anticancer Agents

Abstract

Cancer is the second leading cause of death in the world and one of the major public health problems. Despite the great advances in cancer therapy, the incidence and mortality rates of cancer remain high. Therefore, the quest for more efficient and less toxic cancer treatment strategies is still at the forefront of current research. Curcumin, the active ingredient of the Curcuma longa plant, has received great attention over the past two decades as an antioxidant, anti-inflammatory, and anticancer agent. In this review, a summary of the medicinal chemistry and pharmacology of curcumin and its derivatives in regard to anticancer activity, their main mechanisms of action, and cellular targets has been provided based on the literature data from the experimental and clinical evaluation of curcumin in cancer cell lines, animal models, and human subjects. In addition, the recent advances in the drug delivery systems for curcumin delivery to cancer cells have been highlighted.

Keywords: anticancer; cellular pathway; curcumin; delivery system; mechanism of action; structure activity relationship.

Figure 1

(A) Chemical structure of curcumin. (B) The main pharmacophores and potential substitution positions.

Figure 2

Examples of current nanoparticle design strategies used to improve targeting.

Figure 3

(A) Schematic representation of curcumin-loaded liposomes inducing a reduction in the number of macrophages [62]. HSA: human serum albumin; DPPC: 1, 2-dipalmitoyl-sn-glycero-3-phosphocholine; DPPS: 1, 2-dipalmitoyl-sn-glycero-3-phospho-L-serine. (B) curcumin-loaded liposomes inhibit production of IL-6; white, grey, and black columns represent control, unloaded liposomes, and curcumin-loaded liposomes respectively. Reprinted from Amano et al. [62].

Figure 4

(A) Fabrication of magnetic silk particles (MSP) for curcumin delivery. (B) Atomic force microscopy (AFM) images of MSP before and after curcumin loading. (C) Representative microscopic images of MDA-MB-231 cells incubated with free curcumin and curcumin-loaded MSP showing a significant improvement of curcumin cellular uptake. Reprinted from Song et al. [54], copyright © 2017 ACS.

Figure 5

(A) Schematic structure of cyclodextrin–curcumin (CD–CUR) inclusion and self-assembled complexes (B) Fluorescence-activated cell sorting (FACS) analysis for cellular uptake of curcumin and different CD–CUR (CD5, CD10, CD20, and CD30) inclusion complexes treated in DU145 prostate cancer. * p < 0.05 represents significant difference from the curcumin uptake. Reprinted from Yallapu et al. [86] with permission from the copyright holder Elsevier.

Figure 6

The main molecular targets of curcumin in cancer cells. ↑: Increase; ↓: Decrease; MMP: Matrix metalloproteinase; AP-1: Activation protein-1.