Insights into the Targeting Potential of Thymoquinone for Therapeutic Intervention Against Triple-negative Breast Cancer

Abstract

Background: Thymoquinone (TQ) is a bioactive phytoconstituent obtained from Nigella sativa (black seeds). It has promising potential in cancer prevention.

Objective: Previous studies have shown that TQ can modulate signaling pathways responsible for cancer progression, thus enhancing the efficacy and improving the safety profile of clinically used anticancer drugs.

Method: TQ acts on cell cycle and inhibits progression from G1 to S phase by targeting various proteins (cyclin D1, cyclin E, and p27). It also exhibits histone deacetylase (HDAC) inhibitory effects, targets p21 and Maspin, and induces pro-apoptotic gene, Bax and downregulates anti-apoptotic gene Bcl-2. Breast cancer (BC) is reported as one of the most common malignancies in women.

Results: Despite the research and advancement, it remains one of the most common causes of cancer related deaths among women. Recent advancements in molecular screening of BC led to the identification of clinically challenging condition of triple negative breast cancer (TNBC). TNBC is characterized by the absence of targetable receptors viz. estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) expressions. It is also characterized by reduced or absence of phosphatase and tensin homolog (PTEN) expression, a tumor suppressor gene having diverse functions including regulation of apoptosis, cell cycle, and metastasis.

Conclusion: Since TQ has been reported to up-regulate several growth factors such as vascular endothelial growth factor (VEGF), EGF and PTEN expression, the present review article discusses the targeting potential of TQ for therapeutic intervention against such types of breast cancer.

Keywords: HDAC; TNBC; Thymoquinone; VEGF; apoptosis; black seeds; breast cancer.