Dermatology Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar.
Translational Research Institute, Hamad Medical Corporation, Doha, Qatar.
Leuk Lymphoma. 2023 Dec;64(14):2236-2248. doi: 10.1080/10428194.2023.2256909. Epub 2023 Sep 14.
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.
皮肤 T 细胞淋巴瘤 (CTCL) 是一组影响皮肤的异质性肿瘤。对化疗药物的获得性耐药性和相关的毒性副作用是需要寻找新型 CTCL 药物的限制因素。恩贝素 (EMB) 是一种天然存在的苯醌衍生物，由于其抗癌药理作用和无毒性质而受到关注。我们评估了 EMB 对 CTCL 细胞系 HuT78 和 H9 的抗癌活性。EMB 以剂量依赖性方式抑制 CTCL 细胞的活力。EMB 通过激活起始和执行半胱天冬酶激活细胞凋亡的外在和内在途径。EMB 诱导的细胞凋亡还涉及抑制凋亡抑制剂 XIAP、cIAP1 和 cIAP2。PARP 切割和 pH2AX 的上调表明 EMB 诱导的 DNA 损伤。总之，我们描述了 EMB 对 CTCL 细胞的新型诱导细胞凋亡活性，表明 EMB 是一种有潜力的 CTCL 治疗药物。
