Reverse Screening Bioinformatics Approach to Identify Potential Anti Breast Cancer Targets Using Thymoquinone from Neutraceuticals Black Cumin Oil.
Anticancer Agents Med Chem. 2019 Jan 24. Epub 2019 Jan 24. PMID: 30678630
Functional foods, neutraceuticals and natural antioxidants have established their potential roles in the protection of human health and diseases. Thymoquinone (TQ), the main bioactive component of Nigella sativa seeds (black cumin seeds), a plant derived neutraceutical was used by ancient Egyptians because of their ability to cure a variety of health conditions and used as a dietary food supplement. Owing to its multi targeting nature, TQ interferes with a wide range of tumorigenic processes and counteracts carcinogenesis, malignant growth, invasion, migration, and angiogenesis. Additionally, TQ can specifically sensitize tumor cells towards conventional cancer treatments (e.g., radiotherapy, chemotherapy, and immunotherapy) and simultaneously minimize therapy-associated toxic effects in normal cells besides being cost effective and safe. TQ was found to play a protective role when given along with chemotherapeutic agents to normal cells. In the present study, reverse in silico docking approach was used to search for potential molecular targets for cancer therapy. Various apoptotic targets and DNA repair target were docked with the ligand, TQ. TQ was also tested for its anticancer activities for its ability to cause cell death, arrest cell cycle, DNA damage and ability to inhibit PARP gene expression. In silico docking studies showed that TQ effectively docked apoptotic targets including Trail-R, Bcl-2, MDM2, Bak, Bax and DNA repair target PARP. The docking was more effective with PARP. They were able to bring about cell death mediated by apoptosis, cell cycle arrest in the late apoptotic stage and induce DNA damage too . TQ effectively down regulated PARP gene expression which can lead to enhanced cancer cell death. Thus TQ is a good candidate that can be exploited as a novel neutraceutical for combinatorial therapy to treat breast cancer.