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Diallyl Sulfide-Mediated Modulation of the Fatty Acid Synthase (FASN) Leads to Cancer Cell Death in BaP-Induced Lung Carcinogenesis in Swiss Mice
Journal of Inflammation Research ( IF 4.5 ) Pub Date : 2020-12-08 , DOI: 10.2147/jir.s284279 Arif Khan 1 , Fahad A Alhumaydhi 2 , Ameen S S Alwashmi 2 , Khaled S Allemailem 2 , Mohammed A Alsahli 2 , Faris A Alrumaihi 2 , Ahmad Almatroudi 2 , Mugahid A Mobark 3, 4 , Ayman Mousa 1, 5 , Masood A Khan 1
Journal of Inflammation Research ( IF 4.5 ) Pub Date : 2020-12-08 , DOI: 10.2147/jir.s284279 Arif Khan 1 , Fahad A Alhumaydhi 2 , Ameen S S Alwashmi 2 , Khaled S Allemailem 2 , Mohammed A Alsahli 2 , Faris A Alrumaihi 2 , Ahmad Almatroudi 2 , Mugahid A Mobark 3, 4 , Ayman Mousa 1, 5 , Masood A Khan 1
Affiliation
Purpose: Diallyl sulfide (DAS), one of the organo-sulfur secondary metabolites in garlic, has been shown to inhibit the proliferation of cancer cells. The present study aimed to evaluate the mechanism of DAS in the prevention of benzo[a]pyrene (BaP)-induced lung cancer in a murine model.
Materials and Methods: The mice were exposed to 50 mg/kg of BaP twice a week for 4 weeks in order to induce lung carcinoma. Pretreatment of mice with DAS (100 mg/kg) was started 2 weeks before BaP exposure and further continued for 21 weeks. The effect of DAS and BaP was evaluated by studying various parameters in the serum and tissues of the treated or untreated BaP-exposed mice.
Results: The histopathological findings demonstrated that DAS prevented the progression of malignant lung cancer and metastasis in the liver. A significant drop was observed in BaP-induced tumor marker enzymes (ADA, AHH, γ-GT, LDH) in the serum of the mice treated with DAS. Moreover, DAS treatment resulted in the recovery of antioxidant enzymes, SOD and CAT, in BaP-exposed mice. The induction of apoptosis and the destruction of cellular ROS were detected in cancer cells from the mice pre-treated with DAS. The immunohistochemical analysis revealed the up-regulation of fatty acid synthase (FASN) in the lungs and liver tissues of BaP-exposed mice and the treatment with DAS inhibited FASN expression.
Conclusion: The findings of the present study indicated that DAS-induced apoptosis is strongly associated with the downregulation of FASN in tumor tissues. To the best of our knowledge, this is the first study that describes the role of FASN in BaP-induced lung carcinogenesis.
Keywords: DAS, FASN, apoptosis, ROS, lung carcinoma
中文翻译：
二烯丙基硫醚介导的脂肪酸合酶 (FASN) 调节导致瑞士小鼠 BaP 诱导的肺癌发生中的癌细胞死亡
目的：二烯丙基硫醚 (DAS) 是大蒜中的一种有机硫次生代谢物，已被证明可抑制癌细胞的增殖。本研究旨在评估 DAS 在小鼠模型中预防苯并 [a] 芘 (BaP) 诱导的肺癌的机制。
材料与方法：小鼠每周两次暴露于 50 mg/kg BaP，持续 4 周，以诱导肺癌。在 BaP 暴露前 2 周开始用 DAS (100 mg/kg) 对小鼠进行预处理，并进一步持续 21 周。DAS 和 BaP 的作用是通过研究处理或未处理 BaP 暴露小鼠的血清和组织中的各种参数来评估的。
结果：组织病理学发现表明，DAS 可防止恶性肺癌的进展和肝脏转移。在用 DAS 处理的小鼠的血清中，观察到 BaP 诱导的肿瘤标志物酶（ADA、AHH、γ-GT、LDH）显着下降。此外，DAS 处理导致暴露于 BaP 的小鼠中抗氧化酶 SOD 和 CAT 的恢复。在用 DAS 预处理的小鼠的癌细胞中检测到细胞凋亡的诱导和细胞 ROS 的破坏。免疫组织化学分析显示，暴露于 BaP 的小鼠的肺和肝组织中脂肪酸合酶 (FASN) 上调，DAS 治疗抑制了 FASN 表达。
结论：本研究的结果表明，DAS 诱导的细胞凋亡与肿瘤组织中 FASN 的下调密切相关。据我们所知，这是第一项描述 FASN 在 BaP 诱导的肺癌发生中作用的研究。
关键词： DAS，FASN，细胞凋亡，活性氧，肺癌
更新日期：2020-12-08
Materials and Methods: The mice were exposed to 50 mg/kg of BaP twice a week for 4 weeks in order to induce lung carcinoma. Pretreatment of mice with DAS (100 mg/kg) was started 2 weeks before BaP exposure and further continued for 21 weeks. The effect of DAS and BaP was evaluated by studying various parameters in the serum and tissues of the treated or untreated BaP-exposed mice.
Results: The histopathological findings demonstrated that DAS prevented the progression of malignant lung cancer and metastasis in the liver. A significant drop was observed in BaP-induced tumor marker enzymes (ADA, AHH, γ-GT, LDH) in the serum of the mice treated with DAS. Moreover, DAS treatment resulted in the recovery of antioxidant enzymes, SOD and CAT, in BaP-exposed mice. The induction of apoptosis and the destruction of cellular ROS were detected in cancer cells from the mice pre-treated with DAS. The immunohistochemical analysis revealed the up-regulation of fatty acid synthase (FASN) in the lungs and liver tissues of BaP-exposed mice and the treatment with DAS inhibited FASN expression.
Conclusion: The findings of the present study indicated that DAS-induced apoptosis is strongly associated with the downregulation of FASN in tumor tissues. To the best of our knowledge, this is the first study that describes the role of FASN in BaP-induced lung carcinogenesis.
Keywords: DAS, FASN, apoptosis, ROS, lung carcinoma
中文翻译：
二烯丙基硫醚介导的脂肪酸合酶 (FASN) 调节导致瑞士小鼠 BaP 诱导的肺癌发生中的癌细胞死亡
目的：二烯丙基硫醚 (DAS) 是大蒜中的一种有机硫次生代谢物，已被证明可抑制癌细胞的增殖。本研究旨在评估 DAS 在小鼠模型中预防苯并 [a] 芘 (BaP) 诱导的肺癌的机制。
材料与方法：小鼠每周两次暴露于 50 mg/kg BaP，持续 4 周，以诱导肺癌。在 BaP 暴露前 2 周开始用 DAS (100 mg/kg) 对小鼠进行预处理，并进一步持续 21 周。DAS 和 BaP 的作用是通过研究处理或未处理 BaP 暴露小鼠的血清和组织中的各种参数来评估的。
结果：组织病理学发现表明，DAS 可防止恶性肺癌的进展和肝脏转移。在用 DAS 处理的小鼠的血清中，观察到 BaP 诱导的肿瘤标志物酶（ADA、AHH、γ-GT、LDH）显着下降。此外，DAS 处理导致暴露于 BaP 的小鼠中抗氧化酶 SOD 和 CAT 的恢复。在用 DAS 预处理的小鼠的癌细胞中检测到细胞凋亡的诱导和细胞 ROS 的破坏。免疫组织化学分析显示，暴露于 BaP 的小鼠的肺和肝组织中脂肪酸合酶 (FASN) 上调，DAS 治疗抑制了 FASN 表达。
结论：本研究的结果表明，DAS 诱导的细胞凋亡与肿瘤组织中 FASN 的下调密切相关。据我们所知，这是第一项描述 FASN 在 BaP 诱导的肺癌发生中作用的研究。
关键词： DAS，FASN，细胞凋亡，活性氧，肺癌
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