Embelin inhibits viability of cutaneous T cell lymphoma cell lines HuT78 and H9 by targeting inhibitors of apoptosis

Abstract

Cutaneous T cell lymphoma (CTCL) is a varied group of neoplasms that affects the skin. Acquired resistance against chemotherapeutic drugs and associated toxic side effects are limitations that warrant search for novel drugs against CTCL. Embelin (EMB) is a naturally occurring benzoquinone derivative that has gained attention owing to its anticancer pharmacological actions and nontoxic nature. We assessed the anticancer activity of EMB against CTCL cell lines, HuT78, and H9. EMB inhibited viability of CTCL cells in a dose-dependent manner. EMB activated extrinsic and intrinsic pathways of apoptosis as shown by the activation of initiator and executioner caspases. EMB-induced apoptosis also involved suppression of inhibitors of apoptosis, XIAP, cIAP1, and cIAP2. PARP cleavage and upregulation of pH2AX indicated DNA damage induced by EMB. In conclusion, we characterized a novel apoptosis-inducing activity of EMB against CTCL cells, implicating EMB as a potential therapeutic agent against CTCL.

Keywords:

• Cutaneous T cell lymphoma
• embelin
• apoptosis
• caspases
• inhibitors of apoptosis

Acknowledgments

Open Access funding provided by the Qatar National Library. We thank Ms. Lubna Therachiyil for assisting in the preparation of schematic illustration using BioRender.com.

Disclosure statement

MS is a consultant or advisory board member for Pfizer, Janssen, Eli-Lilly, Novartis, Abbvie, Almirall, Avon, UCB, Celgene, Galderma, Leo, MenloTx, Mitsubishi, Maruho, Toray, Sanofi, Regeneron. Grants by Pfizer, Abbvie, Almirall, Novartis, Leo, Travi, Galderma, Toray, Mitsubishi, Maruho, Avon; Speaker for Pfizer, Janssen, Eli-Lilly, Novartis, Abbvie, UCB, Celgene, Galderma, Leo, MenloTx, Sanofi, Regeneron. All other authors have nothing to disclose.

Additional information

Funding

Supported by the Medical Research Centre (MRC) Fund (MRC-01-21-315), Hamad Medical Corporation, Doha, Qatar.