Department of Burn and Plastic Surgery, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan, China.
Department of Pediatrics, College of Medicine, King Saud University, [Medical City], King Khalid University Hospital, Riyadh, Saudi Arabia.
Environ Toxicol. 2021 May;36(5):800-810. doi: 10.1002/tox.23082. Epub 2020 Dec 21.
Skin cancer is the commonly found type, which contributes to 40% of whole cancer incidences worldwide. Dieckol is an active compound occurs in the marine algae with many biological benefits. In this exploration, we intended to investigate the therapeutic potency of dieckol against the 7,12-dimethylbenz(a)anthracene (DMBA)-triggered skin carcinogenesis in mice. The skin cancer was stimulated to the animals via injecting the 25 μg of DMBA in 100 μL of acetone in shaved dorsal portion along with the 30 mg/kg of dieckol supplementation for 25 week. The antioxidant enzymes and phase-I and -II detoxifying enzymes in the test animals were inspected via standard protocols. Pro-inflammatory markers (IL-6, IL-1β, and TNF-α) level was examined via ELISA kits and the expression of inflammatory molecular markers like p-NF-ƙB, IƙBα and p-IƙBα were studied through western blotting. The expression status of pro- and anti-apoptotic proteins (p53, Bax, Bcl-2, caspase-3, caspase-9, COX-2, TGF-β1) was investigated via real-time polymerase chain reaction (RT-PCR). Our results revealed that the 30 mg/kg of dieckol supplementation noticeably regained the body and liver weight and also diminished the tumor incidence in the DMBA-incited animals. Dieckol treatment exhibited an enhanced antioxidants (SOD, CAT, GPx, and GSH) and reduced phase-I enzymes Cyt-p450 and Cyt-b5 in the DMBA-induced animals. Dieckol also diminished the pro-inflammatory modulators like IL-6, IL-1β and TNF-α. Western blotting result evidenced that the dieckol was inhibited the IƙB/NF-ƙB signaling pathway. RT-PCR study proved the enhanced expression of pro-apoptotic protein (p53, Bax, caspase-3 and -9) in the dieckol treated animals. Histological study also confirmed the therapeutic benefits of Dieckol. Altogether with these findings, it was clear that the dieckol has appreciably allayed the DMBA activated skin tumorigenesis in the mice and it could be a promising agent to treat the human skin cancer in future.
皮肤癌是最常见的类型，占全球癌症发病率的 40%。岩藻依聚糖是一种存在于海洋藻类中的活性化合物，具有许多生物益处。在这项研究中，我们旨在研究岩藻依聚糖对二甲基苯并蒽（DMBA）诱发的小鼠皮肤癌发生的治疗潜力。通过向剃光的背部皮肤中注射 25μg DMBA（溶于 100μL 丙酮），并补充 30mg/kg 岩藻依聚糖，刺激动物产生皮肤癌，共 25 周。通过标准方案检查受试动物的抗氧化酶和 I 相和 II 相解毒酶。通过 ELISA 试剂盒检测促炎标志物（IL-6、IL-1β 和 TNF-α）水平，并通过 Western blot 研究炎症分子标志物如 p-NF-κB、IκBα 和 p-IκBα 的表达。通过实时聚合酶链反应（RT-PCR）研究促凋亡和抗凋亡蛋白（p53、Bax、Bcl-2、caspase-3、caspase-9、COX-2、TGF-β1）的表达状态。我们的结果表明，30mg/kg 岩藻依聚糖补充剂明显恢复了 DMBA 诱导动物的体重和肝脏重量，并降低了肿瘤发生率。岩藻依聚糖处理表现出增强的抗氧化剂（SOD、CAT、GPx 和 GSH）和降低的 DMBA 诱导动物中的 I 相酶 Cyt-p450 和 Cyt-b5。岩藻依聚糖还降低了促炎调节剂，如 IL-6、IL-1β 和 TNF-α。Western blot 结果表明，岩藻依聚糖抑制了 IκB/NF-κB 信号通路。RT-PCR 研究证明，在岩藻依聚糖处理的动物中，促凋亡蛋白（p53、Bax、caspase-3 和 -9）的表达增强。组织学研究也证实了岩藻依聚糖的治疗益处。综上所述，岩藻依聚糖明显缓解了 DMBA 激活的小鼠皮肤肿瘤发生，它可能是未来治疗人类皮肤癌的有前途的药物。
