Study On The Inhibitory Effect Of Plant-derived Extracts On Breast Cancer

As the leading cancer threatening women,breast cancer poses a financial burden that deters patients,but affordable plant-based medicines with abundant energy storage offer a glimmer of hope.Studies have revealed diverse active ingredients in plants for cancer prevention and treatment,yet they lack comprehensive validation and development.In order to explore natural plants as new mechanisms for anti-breast cancer drugs,this study collected 100 plant samples from forests in Henan Province.Through high-throughput screening,Picrasma quassioides D.Don Benn,Buckleya henryi Diels,and Meliosma cuneifolia Franch were identified in three plants with potential active ingredients against breast cancer.Comparing the functional group types and anti-cancer active ingredient variances in different organs and seasonal extracts of three plants,it was determined that Picrasma quassioides exhibits a more significant therapeutic effect against breast cancer.The study systematically analyzed the types,distribution,and relative content of active ingredients in Picrasma quassioides throughout the seasons,examining their impact on breast cancer cell toxicity.It also investigated treatment target proteins and enriched signaling pathways,revealing the mechanism of action of Picrasma quassioides against breast cancer cells.This study provides reliable data and guidance for Picrasma quassioides as a novel anti-cancer drug,promoting its efficient utilization and offering new research directions for utilizing Picrasma quassioides in breast cancer treatment.The main research findings are as follows:（1）The study screened plant-derived extracts for their ability to inhibit the cytotoxicity of MDA-MB-231 breast cancer cells.High-throughput screening of different organs and seasons ethanol extracts from 100 plants using the MTT assay revealed that extracts from Picrasma quassioides,Buckleya henryi and Meliosma cuneifolia effectively suppressed breast cancer cell growth.By employing FTIR to assess the types of functional groups in different organs and seasons of these three plants,it was found that multiple similar absorption peaks were present in the ranges of 3420-2930,2930-2850,and 1740-781 cm^-1across three plant different organs and seasons.The peak intensities varied among the four seasons,with slight positional changes in individual peaks,and Picrasma quassioides exhibited the highest number of characteristic peaks.This preliminary evidence indicates that the three plants contain a rich array of chemical substances,with variations in compound types and relative contents across different organs and seasons,with Picrasma quassioides being the most abundant in compounds.（2）Explored the impact of volatile active ingredients from different organs and seasons of Picrasma quassioides,Buckleya henryi and Meliosma cuneifolia extracts on cell toxicity.GC-MS analysis revealed that all organs of these Picrasma quassioides,Buckleya henryi and Meliosma cuneifolia plants’extracts contain abundant active components such as alcohols,phenols,and acids.From three plants in four seasons collectively contained 2633,2493,and 2333 volatile components,Picrasma quassioides exhibited the richest variety of active ingredients,with 28,31,30,and 16 effective components in different seasons,including bioactive substances with anti-cancer,anti-tumor,and antibacterial properties,such as5-methyl-2-Furancarboxaldehyde,β-elemene,obacunone,panaxydol,and clindamycin.The MTT cytotoxicity assay further confirmed that the extract from Picrasma quassioides exhibited the most significant inhibitory effect on MDA-MB-231 breast cancer cells,with the highest mortality rate reaching 74.32%（P<0.01）.It showed a relatively minor cytotoxic effect on normal human breast cells MCF-10A（24.96%,P<0.01）.The impact of volatile active ingredients with different organs and seasons varied in their cytotoxic effects on MDA-MB-231 breast cancer cells.（3）Explored the differences in non-volatile effective chemical components of different organs and seasonal extracts of Picrasma quassioides.Results from UPLC-QTOF-MS revealed the presence of abundant non-volatile compounds such as glycosides,alkaloids,and phenylpropanoids in different organs and seasons of Picrasma quassioides.Across the four seasons of spring,summer,autumn,and winter,a total of 2405,2191,2923,and 1531 non-volatile components were detected,the highest chemical composition quantity was observed in autumn.Extracts from leaves,branches,bark,trunk,roots,and root bark of trees were found to contain 79,56,69,27,43,and 57 types of non-volatile bioactive compounds with anti-cancer,anti-tumor,and antioxidant properties across the four seasons,including compounds such as3-epibetulinic acid,demethylwedelolactone,dihydroactinidiolide,fuziline,and schizandrin A.Picrasma quassioides’different organs were found to contain unique components across all four seasons with 51,46,53,and 47 types,includingβ-carboline,picrasidine,and nigakilactone,et al,.The inhibitory effect on breast cancer cells by ethanol extracts from Picrasma quassioides tree trunks and root bark in spring is associated with non-volatile active components such as canthin-6-one,palbinone,and chamigrenal,et al.,The impact of different seasons varies in terms of non-volatile components and effective active ingredients,with different substances showing corresponding distribution variances across the seasons.（4）The mechanism of action of Picrasma quassioides extracts on breast cancer MDA-MB-231 cells was elucidated.Using CCK-8 and flow cytometry,it was confirmed that ethanol extracts from the tree trunk and ethanol/water extracts from the root bark of Picrasma quassioides significantly inhibited MDA-MB-231 cells.Both extracts induced apoptosis in MDA-MB-231 cells,with the ethanol extract from the tree trunk showing the most optimal inhibitory effect on MDA-MB-231 cells,achieving a kill rate of 82.743%（P<0.01）and an apoptosis rate of 83.01%（P<0.01）.Further xenograft experiments revealed that these two extracts reduced breast cancer tumor volume by 67.35%and 55.71%in tumor-bearing mice,with a significant decrease in tumor weight by 35.80%and 39.08%.There was no significant difference in the body weight of the tumor-bearing mice before and after treatment with these extracts.Based on network pharmacology protein-protein interaction（PPI）network analysis,it was found that the non-volatile active components,such as baohuoside I,canthin-6-one and chamigrenal,in the two extracts of Picrasma quassioides in spring share multiple common targets with breast cancer.The potential therapeutic targets for breast cancer were identified as 333 and 231.GO enrichment analysis revealed that extracts from Picrasma quassioides can exert inhibitory effects on breast cancer through various pathways,such as peptide-tyrosine phosphorylation,membrane rafts,and protein tyrosine kinase activity.KEGG signaling pathway analysis indicated that these extracts can influence cancer cell proliferation and growth through multiple signaling pathways,including endocrine resistance and neuroactive ligand-receptor interactions.The ethanol extract from the trunk of Picrasma quassioides in spring and the ethanol/water extract from the root bark have been identified to possess the potential to treat breast cancer through various effective bioactive components,multi-target protein interactions,and multiple signaling pathways.This study identified Picrasma quassioides as a new plant source for anti-breast cancer through high-throughput screening of 100 plant species.It detailed the types,relative contents,distribution areas,and efficacy of the effective components in various organs of Picrasma quassioides in different seasons.Additionally,the anti-breast cancer mechanism of the extract of Picrasma quassioides was studied,providing a reliable scientific basis for the use of ethanol extracts from the stems and bark of Picrasma quassioides in spring as oral medications for breast cancer treatment.This research has promoted the efficient utilization of Picrasma quassioides and opened up new research directions for using Picrasma quassioides in the treatment of breast cancer in the future.