Applications of Curcumin and Its Nanoforms in the Treatment of Cancer

Abstract

Due to the diverse medicinal and pharmacokinetic properties of turmeric, it is well-known in the therapeutic, pharmaceutic, nutraceutical, cosmetic, and dietary industries. It gained importance due to its multitude of properties, such as wound-healing, anti-inflammatory, anti-oxidant, anti-microbial, cytoprotective, anti-aging, anti-cancer, and immunomodulatory effects. Even though the natural healing effect of turmeric has been known to Indians as early as 2500 BCE, the global demand for turmeric has increased only recently. A major reason for the beneficiary activities of turmeric is the presence of the yellow-colored polyphenolic compound called curcumin. Many studies have been carried out on the various properties of curcumin and its derivatives. Despite its low bioavailability, curcumin has been effectively used for the treatment of many diseases, such as cardiovascular and neurological diseases, diabetes, arthritis, and cancer. The advent of nanobiotechnology has further opened wide opportunities to explore and expand the use of curcumin in the medical field. Nanoformulations using curcumin and its derivatives helped to design new treatment modalities, specifically in cancer, because of the better bioavailability and solubility of nanocurcumin when compared to natural curcumin. This review deals with the various applications of curcumin nanoparticles in cancer therapy and broadly tries to understand how it affect the immunological status of the cancer cell.

Keywords: anti-cancer; co-stimulation; curcumin; immune checkpoint; immune tolerance; immunomodulation; nanocurcumin; signaling pathways; turmeric.

Figure 1

Turmeric powder. The rhizomes of Curcumin longa are harvested, cooked, dried, and powdered to obtain the aromatic yellow turmeric powder.

Figure 2

Chemical structure of curcuminoids. (A) curcumin, (B) demethoxycurcumin and (C) bis-demethoxycurcumin.

Figure 3

Various types of cancer, which are being treated using curcumin and its nanoforms. (Figure prepared using BioRender.com).

Figure 4

Some of the molecular events and the corresponding molecules in cancer, which are affected by the treatment with curcumin and its nanoform. (NK cells—natural killer cells; CTCs—circulating tumor cells; PD-L1—programmed-death ligand 1; NF-κB—nuclear factor-kB; HIF-1α—hypoxia inducing factor-1α; PTEN—Phosphatase and Tensin Homolog; p53—tumor suppressor protein; Akt—protein kinase B; mTOR—mammalian Target Of Rapamycin; Cdc2—conventional dendritic cell type 2; FOXP3—forkhead box P3; TREG—Regulatory T cells; GITR—Glucocorticoid-induced TNF receptor; ICOS—inducible T-cell co-stimulator; PD1—programmed death 1; CTLA-4—cytotoxic T-lymphocyte associated protein 4; JAK—Janus Kinase; STAT3—signal transducer and activator of transcription; MAPK—Mitogen-activated Protein Kinase; PI3K—Phosphatidylinositol-3-kinase; YAP—Yes-associated protein; JNK—c-Jun N-terminal kinase). (Figure prepared using BioRender.com).

Figure 5

A keyword co-occurrence map reflecting the research hotspot in the field. (Adapted from Zhang et al., 2022 [31], with minor change). The figure created using VOSviewer software (VOSviewer version 1.6.18) for visual analysis reflected the keywords that appeared in publications in recent years, and indicated some of the terms that are currently the hot or cutting-edge research topics in these fields related to curcumin and tumors. Green color represents the keywords that are from the most recent publications, followed by keywords represented in red color. Blue-colored keywords appeared in articles prior to yellow-colored keywords. The larger the size of the circle, the more occurring the keyword is in the articles.

Figure 6

Various nanocarriers, which act as vehicles for delivery of drug molecules.

Figure 7

Therapeutic potential of nanocurcumin—the various nanoforms of curcumin have different effects on diverse disease conditions.