Thymoquinone, as a Novel Therapeutic Candidate of Cancers

Abstract

To date, natural products are widely used as pharmaceutical agents for many human diseases and cancers. One of the most popular natural products that have been studied for anticancer properties is thymoquinone (TQ). As a bioactive compound of Nigella sativa, TQ has shown anticancer activities through the inhibition of cell proliferation, migration, and invasion. The anticancer efficacy of TQ is being investigated in several human cancers such as pancreatic cancer, breast cancer, colon cancer, hepatic cancer, cervical cancer, and leukemia. Even though TQ induces apoptosis by regulating the expression of pro- apoptotic and anti-apoptotic genes in many cancers, the TQ effect mechanism on such cancers is not yet fully understood. Therefore, the present review has highlighted the TQ effect mechanisms on several signaling pathways and expression of tumor suppressor genes (TSG). Data from relevant published experimental articles on TQ from 2015 to June 2020 were selected by using Google Scholar and PubMed search engines. The present study investigated the effectiveness of TQ alone or in combination with other anticancer therapeutic agents, such as tyrosine kinase inhibitors on cancers, as a future anticancer therapy nominee by using nanotechnology.

Keywords: angiogenesis; apoptosis; cancers; nanoparticle; proliferation; thymoquinone.

Figure 1

TQ encapsulated in different nanoparticle formulations. (A) TQ entrapped within the polymeric core of a polymeric nanoparticle. (B) Structure of lipid nanoparticle containing TQ sandwiched between two layers of charged ionizable lipids. (C) The chitosan nanoparticle typically possesses positive surface charges and mucoadhesive properties that can adhere to mucus membranes and release TQ in a sustained release manner.

Figure 2

Major anti-tumorigenic properties of TQ. Apoptosis is induced by TQ in cancer cells through producing ROS, demethylating and re-expressing the TSG. TQ inhibits the survival signaling pathways to reduce carcinogenesis progress rate, and decreases cancer metastasis through regulation of epithelial to mesenchymal transition (EMT).

Figure 3

The double action of TQ on DNA methylation. (A) TQ has the potential to repair the epigenetic aberrations in cancer cells and upregulation of tumor suppressor genes such as p53, p73. It leads to the downregulation of DNA methyltransferase DNMT1. (B) TQ can methylate the CpG islands of genomic DNA.

Figure 4

The effect of TKI and TQ treatment combination on cancer cells. In the absence of TSG-negative regulation due to hypermethylation, there will be constitutive activation of signaling pathways even though TKI has inhibited TK, resulting in resistance to TKI. However, after treatment with TQ, there will be reactivation of Tumor suppressor genes (TSG) resulting in inhibition of signaling pathways leading to suppression of cancer cell proliferation.