title: Diallyl Trisulfide Inhibits Growth of NCI-H460in Vitroandin Vivo, and Ameliorates Cisplatin-Induced Oxidative Injury in the Treatment of Lung Carcinoma in Xenograft Mice.
abstract: Diallyl trisulfide (DATS), an organosulfuric component of garlic oil, exhibits potential anticancer and chemopreventive effects. Cisplatin (DDP), a common chemotherapeutic agent, has provided great therapeutic contributions to treating solid tumors, but with serious side effects. Here, we verified the anti-tumor properties of DATS on lung cancerin vitroandin vivo, and evaluated synergistic effects of DATS combined with DDP on the NCI-H460 xenograft model. Significantly decreased cell viabilities, cell cycle G1arrest, and apoptosis induction were observed in DATS treated NCI-H460 cells (p<0.05). And injection of DATS (30 or 40 mg/kg) to female Balb/c mice significantly inhibited the growth of human NCI-H460 cell tumor xenograft (p<0.001). Moreover, DATS in combination with DDP exhibited enhanced anti-tumor activity via induction of apoptosis. Apoptosis pathways were confirmed by modulation of p53, Bcl-2 family members; induction of active caspase-3/8/9 and activation of JNK- and p38-MAPK pathways. Interestedly, DATS+DDP administration exerted fewer side effects, such as suppressing the weight loss and ameliorating DDP-induced oxidative injury, especially in renal parenchyma. In addition, increased E-cadherin and decreased MMP-9 expression levels were observed in DATS-treated tumor tissues. These studies provide supports that DATS might be a potential candidate for combination with DDP in cancer treatment.
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, P.R. China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Jiang
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, P.R. China.
authors.forename: Xiaosong
authors.initials: X
authors.lastname: Zhu
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, P.R. China.
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, P.R. China.
authors.forename: Hongya
authors.initials: H
authors.lastname: Xu
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, P.R. China.; Shandong Provincial Key Laboratory of Mucosal and Transdermal Drug Delivery Technologies, Shandong Academy of Pharmaceutical Sciences, 989 Xinluo Street, Jinan, Shandong 250101, P.R. China.; Jiangsu Shengshi Kangde Biotech Corporation, Lianyungang, Jiangsu 222006, P.R. China.
authors.forename: Zhongxi
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, P.R. China.
authors.forename: Siying
authors.initials: S
authors.lastname: Li
authors.affiliation: Jiangsu Shengshi Kangde Biotech Corporation, Lianyungang, Jiangsu 222006, P.R. China.
authors.forename: Shanzhong
authors.initials: S
authors.lastname: Li
authors.affiliation: Jiangsu Shengshi Kangde Biotech Corporation, Lianyungang, Jiangsu 222006, P.R. China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Cai
authors.affiliation: Jiangsu Shengshi Kangde Biotech Corporation, Lianyungang, Jiangsu 222006, P.R. China.
authors.forename: Jimin
authors.initials: J
authors.lastname: Cao
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015820:Cadherins / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D013440:Sulfides / Q000494:pharmacology / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000498:Allyl Compounds; D000970:Antineoplastic Agents; D015820:Cadherins; D013440:Sulfides; C042577:diallyl trisulfide; D053148:Caspase 3; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9; D002945:Cisplatin
keywords: Diallyl trisulfide; attenuate side effect.; cisplatin; enhanced effect; lung carcinoma