Shenqi Sanjie Granules induce Hmox1-mediated ferroptosis to inhibit colorectal cancer
文献类型：期刊论文
| 作者 | Chen, Meng2,3; Ma, Shengli2; Ji, Wenbo1,3; Hu, Weihua4; Gao, Jiguang2; Yang, Jianke2; Liu, Yu1,3; Cui, Qianwen1,3; Yang, Shasha3; Xu, Xiaohui2 |
| 刊名 | HELIYON
 |
| 出版日期 | 2024-09-30 |
| 卷号 | 10 |
| 关键词 | Chinese herbal medicine Shenqi Sanjie granules Hmox1 Ferroptosis Colorectal cancer Quercetin Luteolin Kaempferol |
| DOI | 10.1016/j.heliyon.2024.e38021 |
| 通讯作者 | Xu, Xiaohui(xhxu@wnmc.edu.cn) ; Dai, Haiming(daih@cmpt.ac.cn) ; Hu, Lei(huleiup@wnmc.edu.cn) |
| 英文摘要 | Background: Because adverse reactions or drug resistance are often found after current chemotherapies for metastatic colorectal cancer (mCRC), new treatments are still in demand. Shenqi Sanjie Granules (SSG), an antitumor compound preparation of traditional Chinese medicine, has been recognized for its ability in clinical practice of oncotherapy. Nevertheless, the precise effects of SSG in colorectal cancer (CRC) and underlying mechanisms through which SSG inhibits CRC remain uncertain. The current study aimed to evaluate the anti-CRC activity of the Chinese herbal compound preparation SSG and investigate the underlying mechanisms of action. Materials and methods: Initially, nine distinct cancer cell lines, including five CRC cell lines, one breast cancer cell line, two lung adenocarcinoma cell lines and one cervical cancer cell line, were used to evaluate the antitumor activity of SSG, and the mouse CRC cell line CT26 were used for further research. In vitro experiments utilizing diverse assays were conducted to assess the inhibitory effects of the SSG on CT26. Furthermore, subcutaneous syngeneic mouse model and AOM (azoxymethane)/DSS (dextran sodium sulfate) induced in-situ colitis-related mouse CRC model were used to evaluate the antitumor potential and biotoxicity of SSG in vivo. To elucidate the underlying molecular mechanisms, transcriptome sequencing and network pharmacology analysis were performed. Meanwhile, verification is carried out with quantitative real-time PCR (qRT-PCR) and flow cytometry (FCM) analysis. Results: Our in vitro inhibition study showed that SSG could effectively inhibit CRC cell line CT26 growth and metastasis, and induce cell death. Neither of apoptosis inhibitor, necroptosis inhibitor, ferroptosis inhibitor, but the combination of the three diminished SSG-induced cell death, suggesting that multiple cell death pathways were involved. Both the syngeneic CRC model and the in-situ CRC model indicated SSG inhibited CRC in vivo with few toxic side effects. Further mechanistic study suggested SSG treatment activated the ferroptosis pathway, particularly mediated by Hmox1, which was upregulated scores of times. Network pharmacology analysis indicated that the active ingredients of SSG, including Quercetin, Luteolin and Kaempferol were potential components directly upregulated Hmox1 expression. Conclusions: Collectively, our findings indicate that the administration of SSG has the potential to inhibit CRC both in vitro and in vivo. The mechanism by which this compound preparation exerts its action is, at least partly, the induction of ferroptosis through upregulating Hmox-1 by its three active ingredients Quercetin, Luteolin and Kaempferol. |
| WOS关键词 | CELL-DEATH ; MECHANISMS ; RESISTANCE |
| 资助项目 | Key Scientific Research Project of Wannan Medical College[WK2022Z01] ; Wuhu Science and Technology Achievement Transformation Project[2022cg24] ; Natural Science Foundation of the Higher Education Institutions of Anhui Province[2022AH051223] ; Key projects of Anhui Provincial Health Commission[AHWJ2022a002] ; Anhui Provincial Department of Education's Scientific Research and Innovation Team[2023AH010072] ; Anhui Provincial Natural Science Foundation[2208085MH221] ; National Natural Science Foundation of China[31970701] ; Anhui Provincial Key RD D Program[202104a07020007] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:001320133500001 |
| 出版者 | CELL PRESS |
| 资助机构 | Key Scientific Research Project of Wannan Medical College ; Wuhu Science and Technology Achievement Transformation Project ; Natural Science Foundation of the Higher Education Institutions of Anhui Province ; Key projects of Anhui Provincial Health Commission ; Anhui Provincial Department of Education's Scientific Research and Innovation Team ; Anhui Provincial Natural Science Foundation ; National Natural Science Foundation of China ; Anhui Provincial Key RD D Program |
| 源URL | [http://ir.hfcas.ac.cn:8080/handle/334002/135758]  |
| 专题 | 中国科学院合肥物质科学研究院 |
| 通讯作者 | Xu, Xiaohui; Dai, Haiming; Hu, Lei |
| 作者单位 | 1.Univ Sci & Technol China, Hefei 230026, Peoples R China 2.Wannan Med Coll, Sch Basic Med Sci, Wuhu 241002, Peoples R China 3.Chinese Acad Sci, Anhui Prov Key Lab Med Phys & Technol, Inst Hlth & Med Technol, Hefei Inst Phys Sci, Hefei 230031, Peoples R China 4.Wannan Med Coll, Reprod Med Ctr, Affiliated Hosp 1, Wuhu 241001, Peoples R China |
| 推荐引用方式 GB/T 7714 | Chen, Meng,Ma, Shengli,Ji, Wenbo,et al. Shenqi Sanjie Granules induce Hmox1-mediated ferroptosis to inhibit colorectal cancer[J]. HELIYON,2024,10. |
| APA | Chen, Meng.,Ma, Shengli.,Ji, Wenbo.,Hu, Weihua.,Gao, Jiguang.,...&Hu, Lei.(2024).Shenqi Sanjie Granules induce Hmox1-mediated ferroptosis to inhibit colorectal cancer.HELIYON,10. |
| MLA | Chen, Meng,et al."Shenqi Sanjie Granules induce Hmox1-mediated ferroptosis to inhibit colorectal cancer".HELIYON 10(2024). |
入库方式： OAI收割
来源：合肥物质科学研究院
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