Abstract
BackgroundTriple-negative breast cancer (TNBC) is a kind of malignant tumor with higher recurrence and metastasis rate. According to historical records, the dry rhizomes Cyperus rotundus L. could be ground into powder and mixed with ginger juice and wine for external application for breast cancer. We studied the effect of the ethanol extract of Cyperus rotundus L. (EECR) on TNBC cells and found its’ apoptosis-inducing effect with a dose-relationship. But the function mechanism of EECR on TNBC is still mysterious. Hence, the present research aimed to detect its function mechanism at the small molecule level through ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) metabolomics.MethodsThe CCK-8 assay and the Annexin V-FITC/PI assay were applied to test the effect of EECR on MDA-MB-231 cells and MDA-MB 468 cells at various concentrations of 0, 200, 400, and 600 μg/ml. UPLC-Q-TOF-MS/MS based metabolomics was used between the control group and the EECR treatment groups. Multivariate statistical analysis was used to visualize the apoptosis-inducing action of EECR and filtrate significantly changed metabolites.ResultsThe apoptosis-inducing action was confirmed and forty-nine significantly changed metabolites (VIP > 1, p < 0.05, and FC > 1.2 or FC < 0.8) were identified after the interference of EECR. The level of significant differential metabolites between control group, middle dose group, and high dose group were compared and found that which supported the apoptosis-inducing action with dose-dependence.ConclusionBy means of metabolism, we have detected the mechanism of EECR inducing apoptosis of TNBC cells at the level of small molecule metabolites and found that EECR impacted the energy metabolism of TNBC cells. In addition, we concluded that EECR induced apoptosis by breaking the balance between ATP-production and ATP-consumption: arresting the pathways of Carbohydrate metabolism such as Central carbon metabolism in cancer, aerobic glycolysis, and Amino sugar and nucleotide sugar metabolism, whereas accelerating the pathways of ATP-consumption including Amino Acids metabolism, Fatty acid metabolism, Riboflavin metabolism and Purine metabolism. Although further study is still needed, EECR has great potential in the clinical treatment of TNBC with fewer toxic and side effects.
Highlights
Triple-negative breast cancer (TNBC) is a kind of malignant tumor with higher recurrence and metastasis rate
We identified 21 phytochemical compounds in the ethanol extract Cyperus rotundus L.(EECR) and found that ethanol extract of Cyperus rotundus L. (EECR) induced TNBC cell apoptosis which is reflected by the enhancement of ratio of the Bax/Bcl-2 [10]
Materials and chemicals The dry rhizomes of Cyperus rotundus L. were purchased from Anhui Xiehecheng Co., Ltd. (Bozhou, China); the ethanol extract of Cyperus rotundus L. was acquired referring to previous reporting method [10]; Dulbecco’s modified Eagle’s medium (DMEM), penicillin, and streptomycin were purchased from Nanjing KeyGen Biotech
Summary
Triple-negative breast cancer (TNBC) is a kind of malignant tumor with higher recurrence and metastasis rate. Breast cancer has a high cure rate when detected early and treated according to best practices, triple-negative breast cancer (TNBC) is an exception due to its lack expression characteristic of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (Her-2). Patients with TNBC have an increased likelihood of distant recurrence and death They cannot be treated with endocrine therapy or Her-2 targeted therapies [1, 2]. Along with an earlier age-of-onset and more probability of the ‘triple-negative’ phenotype, an effective drug with low toxicity is always in demand during the treatment of breast cancer [3,4,5]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
