Thymoquinone: fifty years of success in the battle against cancer models

•This year marks 50 years since thymoquinone was isolated from black seed.•Thymoquinone has had a long history of battling cancer in vitro and in vivo.•Thymoquinone modulates nine of the ten hallmarks of cancer.•There are no controlled Phase I clinical studies on thymoquinone in human tumors.

Thymoquinone (TQ), the main active constituent of black seed essential oil, exhibits promising effects against inflammatory diseases and cancer. TQ, modulates signaling pathways that are key to cancer progression, and enhances the anticancer potential of clinical drugs while reducing their toxic side effects. Considering that TQ was isolated 50 years ago, this review focuses on TQ's chemical and pharmacological properties and the latest advances in TQ analog design and nanoformulation. We discuss our current state of knowledge of TQ's adjuvant potential and in vivo antitumor activity and highlight its ability to modulate the hallmarks of cancer.