Types Of Breast Cancer Cells Research Articles

Impact of estrogen and progesterone hormone receptors on the progression of interferon-γ sensitized breast cancer cells

Background: Breast cancer is a chronic complex disease. Its progression depends partly on the interaction between tumor and immune cells. Whilst immunotherapy is the new promising treatment, many patients with breast cancer acquire resistance. Interferon gamma (IFN-γ) is a pleiotropic cytokine that is primarily released by T cells and natural killer (NK) cells and has always been praised for its antitumor activities. However, IFN-γ may induce different modulations in breast cancer cells that are expressing or not expressing the hormone receptors estrogen and progesterone. Methods: In this study, to examine the effect of IFN-γ on the subtypes of breast cancer in relation to the expression of estrogen and progesterone genes, we performed RNA-sequencing on the triple negative cells MDA-MB231 and ER/PR transfected MDA-MB231 cells (untreated or treated with 100 ng/ml IFN-γ). Various bioinformatics analyses were performed to investigate the affected functional pathways, and immune genes related to the different types of breast cancer cells. Results: The set of differentially expressed genes (DEGs) that are regulated by IFN-γ were unique, and specific to each breast cancer subtype. These unique DEG patterns in hormone-positive cells (GBP3, HLA-DPA1, HLA-DRB1, HLA-E, IL6) and triple negative cells (IFI6, ISG15, CCL5) showed significant but distinct effects on patients’ overall survival as well as noticeable differences in immune modulation and regulation. Conclusions: IFN-γ signaling can differentially affect the pattern of gene expression in breast cancer cells in an estrogen receptor (ER) / progesterone receptor (PR)-dependent manner. IFN-γ treatment of ER+/PR+ breast cancer cells upregulated the expression of genes related to immune cells and showed improved patient prognosis, while TNBC showed negative regulation of the expression of genes related to immune cells and worse patient prognosis.

Breast Cancer Cell Type and Biomechanical Properties of Decellularized Mouse Organs Drives Tumor Cell Colonization.

Tissue engineering has emerged as an indispensable tool for the reconstruction of organ-specific environments. Organ-derived extracellular matrices (ECM) and, especially, decellularized tissues (DCL) are recognized as the most successful biomaterials in regenerative medicine, as DCL preserves the most essential organ-specific ECM properties such as composition alongside biomechanics characterized by stiffness and porosity. Expansion of the DCL technology to cancer biology research, drug development, and nanomedicine is pending refinement of the existing DCL protocols whose reproducibility remains sub-optimal varying from organ to organ. We introduce a facile decellularization protocol universally applicable to murine organs, including liver, lungs, spleen, kidneys, and ovaries, with demonstrated robustness, reproducibility, high purification from cell debris, and architecture preservation, as confirmed by the histological and SEM analysis. The biomechanical properties of as-produced DCL organs expressed in terms of the local and total stiffness were measured using our facile methodology and were found well preserved in comparison with the intact organs. To demonstrate the utility of the developed DCL model to cancer research, we engineered three-dimensional tissue constructs by recellularization representative decellularized organs and collagenous hydrogel with human breast cancer cells of pronounced mesenchymal (MDA-MB-231) or epithelial (SKBR-3) phenotypes. The biomechanical properties of the DCL organs were found pivotal to determining the cancer cell fate and progression. Our histological and scanning electron microscopy (SEM) study revealed that the larger the ECM mean pore size and the smaller the total stiffness (as in lung and ovary), the more proliferative and invasive the mesenchymal cells became. At the same time, the low local stiffness ECMs (ranged 2.8-3.6 kPa) did support the epithelial-like SKBR-3 cells' viability (as in lung and spleen), while stiff ECMs did not. The total and local stiffness of the collagenous hydrogel was measured too low to sustain the proliferative potential of both cell lines. The observed cell proliferation patterns were easily interpretable in terms of the ECM biomechanical properties, such as binding sites, embedment facilities, and migration space. As such, our three-dimensional tissue engineering model is scalable and adaptable for pharmacological testing and cancer biology research of metastatic and primary tumors, including early metastatic colonization in native organ-specific ECM.

Invitro antioxidant and anticancer activities of Smilax corbularia extract combined with Phellinus linteus extract against breast cancer cell lines.

Treatment with extracts from whole herbs has been reported to synergistically enhance the anticancer activities of therapeutic agents in recent studies. The present study evaluated the antioxidant and anticancer activities of Smilax corbularia Kunth (S. corbularia) and Phellinus linteus (P. linteus) crude extracts individually and in combination. S. corbularia was extracted using ethanol, whereas P. linteus was extracted using hot water. Both crude extracts underwent physiochemical characterization. Subsequently, the possible antioxidant activities of both crude extracts, individually and in combination, were evaluated using 2,2-Diphenyl-1-picrylhydrazyl and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) assays. Their effects on breast cancer cell cytotoxicity, proliferation and apoptosis were then assessed. The crude S. corbularia extract obtained was found to have a high level of total phenolic content, whilst the crude P. linteus extract had high levels of total polysaccharide content. The total phenolic content and total polysaccharide content results of the combinations depended on the respective ratios of the individual extracts. S. corbularia alone and combination 3 (which contained 75% S. corbularia: 25% P. linteus) demonstrated the greatest radical scavenging activity, followed by combination 1 (50% S. corbularia: 50% P. linteus), combination 2 (25% S. corbularia: 75% P. linteus) and P. linteus. The toxicity results of the extract samples on the cancer cells corresponded with their antioxidant activity. In particular, certain combinations demonstrated clearer inhibitory effects on cell proliferation against three types of breast cancer cells compared with those exerted by the two individual extracts. However, induction of apoptosis was limited, with the degree of apoptosis observed to be #x003C;5%. These findings suggested that treatment with combinations of these two extracts could confer enhanced antioxidant and antiproliferative effects on breast cancer cells. Therefore, the potential of these two extracts in combination as anticancer agents warrants further investigation.

Estrogen receptor status heterogeneity in breast cancer tumor: role in response to endocrine treatment.

Tumor heterogeneity affects diagnosis, prognosis and response to therapy. Heterogeneity is found in both normal and neoplastic human mammary gland. Indeed, luminal ER-negative cells can give rise to various phenotypes, including ER-negative and ER-positive mammary tumors. As a result, the tumor phenotype does not necessarily reflects the cell of origin of cancer. With regard to the ER status, heterogeneity can challenge endocrine therapies, where the elimination of responsive clones could lead to reduced treatment efficacy and tumor relapse through the expansion of the resistant clones. The aim of this study was to investigate breast tumor heterogeneity and its role in endocrine resistance onset. For this purpose, we used ER+ (T47D, CAMA1) and triple-negative breast cancer cell lines (TNBC; MDA-MB-231, HCC70), co-cultures using 2D and 3D models. Our results showed that ER status is modulated when ER+ cells are cultured in the presence of TNBC cells, leading to a different response to endocrine therapy, demonstrating that the response to treatment can be affected by the influence that different breast cancer cell types exert on each other. In addition, ER+ positive cells doubling time was modified after exposure to TNBC cell co-culturing. Further experiments are required to fully elucidate the molecular mechanism of these observations.

Molecularly Engineered Surfactin Analogues Induce Nonapoptotic-Like Cell Death and Increased Selectivity in Multiple Breast Cancer Cell Types.

Surfactin, a negatively charged amphiphilic lipopeptide biosurfactant, is synthesized by the bacterium Bacillus subtilis. It consists of a cyclic heptapeptide and an 11-15C β-hydroxy fatty acid. To probe how the modification of the molecular skeleton of surfactin influences its selectivity and activity against breast cancer, six synthetic surfactins were generated. Modifications were accomplished by conjugating amine-functionalized molecules to the Glu and Asp carboxyl moieties of the heptapeptide. The resulting synthetic surfactins provided a diverse series of molecules with differences in charge, size, and hydrophilicity. After purification and structural analysis, insights into biological activity and specificity were generated for each compound. Dose-dependent growth inhibition was determined for four tumorigenic breast cancer cell lines in monolayer and spheroid morphologies, as well as nontumorigenic fibroblasts and sheep erythrocytes, which were utilized to determine selectivity indices. Results indicated that two compounds, which have amplified anionic charge, had increased activity on breast cancer, with reduced activity on nontumorigenic fibroblasts and erythrocytes. Cationic derivative surf-ethylenediamine has increased activity on all cell lines tested. Novel correlations between dose-response activities and physicochemical properties of all compounds determined that there is a significant correlation between the critical micelle concentration and activity against multiple cell lines.

Development and Characterization of Folic Acid-Conjugated Amodiaquine-Loaded Nanoparticles–Efficacy in Cancer Treatment

The objective of this study was to construct amodiaquine-loaded, folic acid-conjugated polymeric nanoparticles (FA-AQ NPs) to treat cancer that could be scaled to commercial production. In this study, folic acid (FA) was conjugated with a PLGA polymer followed by the formulation of drug-loaded NPs. The results of the conjugation efficiency confirmed the conjugation of FA with PLGA. The developed folic acid-conjugated nanoparticles demonstrated uniform particle size distributions and had visible spherical shapes under transmission electron microscopy. The cellular uptake results suggested that FA modification could enhance the cellular internalization of nanoparticulate systems in non-small cell lung cancer, cervical, and breast cancer cell types. Furthermore, cytotoxicity studies showed the superior efficacy of FA-AQ NPs in different cancer cells such as MDAMB-231 and HeLA. FA-AQ NPs had better anti-tumor abilities demonstrated via 3D spheroid cell culture studies. Therefore, FA-AQ NPs could be a promising drug delivery system for cancer therapy.

Thiosemicarbazide Derivatives Targeting Human TopoIIα and IDO-1 as Small-Molecule Drug Candidates for Breast Cancer Treatment.

In 2020, breast cancer became the most frequently diagnosed type of cancer, with nearly 2.3 million new cases diagnosed. However, with early diagnosis and proper treatment, breast cancer has a good prognosis. Here, we investigated the effect of thiosemicarbazide derivatives, previously identified as dual inhibitors targeting topoisomerase IIα and indoleamine-2,3-dioxygenase 1 (IDO 1), on two distinct types of breast cancer cells (MCF-7 and MDA-MB-231). The investigated compounds (1-3) selectively suppressed the growth of breast cancer cells and promoted apoptosis via caspase-8- and caspase-9-related pathways. Moreover, these compounds caused S-phase cell cycle arrest and dose-dependently inhibited the activity of ATP-binding cassette transporters (MDR1, MRP1/2 and BCRP) in MCF-7 and MDA-MB-231 cells. Additionally, following incubation with compound 1, an increased number of autophagic cells within both types of the investigated breast cancer cells was observed. During preliminary testing of ADME-Tox properties, the possible hemolytic activities of compounds 1-3 and their effects on specific cytochrome P450 enzymes were evaluated.

Deep learning-based phenotyping of breast cancer cells using lens-free digital in-line holography.

Lens-free digital in-line holography (LDIH) produces cellular diffraction patterns (holograms) with a large field of view that lens-based microscopes cannot offer. It is a promising diagnostic tool allowing high-throughput cellular analysis. Holograms are, however, too complicated to discern by the human eye, and time-consuming computation is required to recover object images. To directly analyze holograms from LDIH, we developed a novel deep learning architecture called a holographical deep learning network (HoloNet) for cellular phenotyping. The HoloNet extracts large features from diffraction patterns, integrates them with small features from convolutional layers, and outperforms other state-of-the-art deep learning methods for the classification of breast cancer cells as well as the prediction of the intensities of breast cancer markers, ER/PR and HER2 from raw holograms. Moreover, to identify previously unknown subclusters of breast cancer cells, we developed the feature-fusion HoloNet model to integrate diffraction features related to breast cancer cell types and marker intensities of ER/PR and HER2. This hologram embedding allowed us to identify the subclusters within the known breast cancer cells. Some of the subclusters identified in our study have phenotypes shared by multiple breast cancer cell types since they are located near the class boundaries in the feature space. Identifying such rare and subtle phenotypes of breast cancer cells will enable us to perform detailed analyses of the heterogeneity of cell phenotypes for precise breast cancer diagnosis.

Targeted Drug Delivery Using a Plug-to-Direct Antibody-Nanogel Conjugate.

Targeted drug delivery using antibody-drug conjugates has attracted great attention due to its enhanced therapeutic efficacy compared to traditional chemotherapy. However, the development has been limited due to a low drug-to-antibody ratio and laborious linker-payload optimization. Herein, we present a simple and efficient strategy to combine the favorable features of polymeric nanocarriers with antibodies to generate an antibody-nanogel conjugate (ANC) platform for targeted delivery of cytotoxic agents. Our nanogels stably encapsulate several chemotherapeutic agents with a wide range of mechanisms of action and solubility. We showcase the targetability of ANCs and their selective killing of cancer cells over-expressing disease-relevant antigens such as human epidermal growth factor receptor 2, epidermal growth factor receptor, and tumor-specific mucin 1, which cover a broad range of breast cancer cell types while maintaining low to no toxicity to non-targeted cells. Overall, our system represents a versatile approach that could impact next-generation nanomedicine in antibody-targeted therapeutics.

Mebendazole Increases Anticancer Activity of Radiotherapy in Radiotherapy-Resistant Triple-Negative Breast Cancer Cells by Enhancing Natural Killer Cell-Mediated Cytotoxicity

Breast cancer is the most commonly diagnosed cancer worldwide and ranks first in terms of both prevalence and cancer-related mortality in women. In this study, we aimed to evaluate the anticancer effect of mebendazole (MBZ) and radiotherapy (RT) concomitant use in triple-negative breast cancer (TNBC) cells and elucidate the underlying mechanisms of action. Breast cancer mouse models and several types of breast cancer cells, including TNBC-derived RT-resistant (RT-R) MDA-MB-231 cells, were treated with MBZ and/or RT. In mice, changes in body weight, renal and liver toxicity, tumor volume, and number of lung metastases were determined. In cells, cell viability, colony formation, scratch wound healing, Matrigel invasion, and protein expression using western blotting were determined. Our findings showed that MBZ and RT combined treatment increased the anticancer effect of RT without additional toxicity. In addition, we noted that cyclin B1, PH2AX, and natural killer (NK) cell-mediated cytotoxicity increased following MBZ + RT treatment compared to unaided RT. Our results suggest that MBZ + RT have an enhanced anticancer effect in TNBC which acquires radiation resistance through blocking cell cycle progression, initiating DNA double-strand breaks, and promoting NK cell-mediated cytotoxicity.

Nanotechnology-based electrochemical biosensors for monitoring breast cancer biomarkers.

Breast cancer is categorized as the most widespread cancer type among women globally. On-time diagnosis can decrease the mortality rate by making the right decision in the therapy procedure. These features lead to a reduction in medication time and socioeconomic burden. The current review article provides a comprehensive assessment for breast cancer diagnosis using nanomaterials and related technologies. Growing use of the nano/biotechnology domain in terms of electrochemical nanobiosensor designing was discussed in detail. In this regard, recent advances in nanomaterial applied for amplified biosensing methodologies were assessed for breast cancer diagnosis by focusing on the advantages and disadvantages of these approaches. We also monitored designing methods, advantages, and the necessity of suitable (nano) materials from a statistical standpoint. The main objective of this review is to classify the applicable biosensors based on breast cancer biomarkers. With numerous nano-sized platforms published for breast cancer diagnosis, this review tried to collect the most suitable methodologies for detecting biomarkers and certain breast cancer cell types.

Von Willebrand factor and cancer: Another piece of the puzzle

Von Willebrand factor and cancer: Another piece of the puzzle

Inorganic arsenic in drinking water and breast cancer risk: a case-control study in Northern Chile

BACKGROUND AND AIM: Exposure to arsenic in drinking water is a well-established cause of lung, bladder and skin cancer, however the relation between arsenic and breast cancer is less clear. Between 2014-2018, we conducted a breast cancer incident case-control study in Northern Chile, where from 1950-1970 the population was exposed to high levels of arsenic in drinking water (up to 900 μg/l). METHODS: We analyzed 703 breast cancer cases and 491 population-based female controls with data collected on lifetime exposure to As and potential confounders. Using logistic regression, we tested whether exposure to higher levels of arsenic in drinking water related to differential risk of breast cancer. Initial causal models adjusted for age and education. Additional models included other known risk factors for breast cancer and several sensitivity analyses evaluated different exposure windows. RESULTS: Both cases and controls were around 58 years of age and about half had finished high school or had additional studies. Cases, compared to controls, were exposed to lower median concentrations of arsenic (μg/L): 60 [interquartile range (IQR), 11-636] versus 70 (40-299). Adjusted odds ratios for category of highest single-year arsenic concentrations in water (<49, 50-199, 200-799, and ≥ 800 μg/L) were 1.00, 0.70 [95% confidence interval (CI), 0.52-0.94], 0.71 (0.51-1.01), and 1.02 (0.72-1.44), respectively. Results were similar after various adjustments, using different metrics of arsenic exposure, and windows of exposure. CONCLUSIONS: Compared with women with the lowest levels of exposure to arsenic in drinking water, those with higher (up to 799 μg/L) arsenic exposure, had lower odds of breast cancer, in accordance with evidence implying a potentially therapeutic effect of arsenic exposure. Differential arsenic sensitivity of breast cancer cell types may explain differences in the direction of the effect and lack of precision for some exposure groups. KEYWORDS: arsenic, breast cancer, drinking water

Dielectrophoresis-Based SERS Sensors for the Detection of Cancer Cells in Microfluidic Chips.

The detection of freely circulating cancer cells (CTCs) is one of the greatest challenges of modern medical diagnostics. For several years, there has been increased attention on the use of surface-enhanced Raman spectroscopy (SERS) for the detection of CTCs. SERS is a non-destructive, accurate and precise technique, and the use of special SERS platforms even enables the amplification of weak signals from biological objects. In the current study, we demonstrate the unique arrangement of the SERS technique combined with the deposition of CTCs cells on the surface of the SERS platform via a dielectrophoretic effect. The appropriate frequencies of an alternating electric field and a selected shape of the electric field can result in the efficient deposition of CTCs on the SERS platform. The geometry of the microfluidic chip, the type of the cancer cells and the positive dielectrophoretic phenomenon resulted in the trapping of CTCs on the surface of the SERS platform. We presented results for two type of breast cancer cells, MCF-7 and MDA-MB-231, deposited from the 0.1 PBS solution. The limit of detection (LOD) is 20 cells/mL, which reflects the clinical potential and usefulness of the developed approach. We also provide a proof-of-concept for these CTCs deposited on the SERS platform from blood plasma.

Dose-time and Source-Dependent Analysis of Intraoperative Radiotherapy-Treated Seroma on Breast Cancer Cell Types: A Pilot Study

Background: Intraoperative radiation therapy (IORT) is a novel approach to breast cancer (BC) treatment. Objectives: In this study, we compared the cellular and molecular effects of IORT-treated post-lumpectomy wound fluid (seroma) at the point of IOeRT versus IOxRT on the BC cell line. Methods: Immortalized human BC cell lines: MCF-7, MDA-MB-231, and MCF10 were incubated with seroma from 3 groups of patients (as a pilot study). The first group received Intraoperative electron radiation therapy (IOeRT, Boost dose=12Gy), the second one received IOeRT (Radical dose=21Gy), and the third group was prescribed Intraoperative x-ray radiation therapy (IOxRT, X-ray=20Gy). Cellular and molecular tests were used to investigate how cells are influenced by the IORT-treated seroma. Results: We evaluated the effects of dose-time and source-dependent IORT-treated seroma on BC cell lines. In this study, we observed that IOxRT-treated seroma has the most significant effects on the reduction of proliferation, induced cell cycle arrest, and apoptosis. Furthermore, inhibited migration and invasion of BC cell lines were compared to IOeRT -treated seroma. Conclusions: Although this is a pilot study, we suggest that at 24 h, the IORT (specifically IOxRT)-treated seroma may play an important protective role in the breast tumor bed, which is followed by local recurrence decreases.

The mitochondrial enzyme FAHD1 regulates complex II activity in breast cancer cells and is indispensable for basal BT-20 cells in vitro.

The mitochondrial enzyme fumarylacetoacetate hydrolase domain-containing protein 1 (FAHD1) was identified to be upregulated in breast cancer tissues. Here, we show that FAHD1 is indispensable for the survival of BT-20 cells, representing the basal breast cancer cell type. A lentiviral knock-down of FAHD1 in the breast cancer cell lines MCF-7 and BT-20 results in lower succinate dehydrogenase (complex II) activity. In luminal MCF-7 cells, this leads to reduced proliferation when cultured in medium containing only glutamine as the carbon source. Of note, both cell lines show attenuated protein levels of the enzyme glutaminase (GLS) which activates programmed cell death in BT-20. These findings demonstrate that FAHD1 is crucial for the functionality of complex II in breast cancer cells and acts on glutaminolysis in the mitochondria.

Dual-miRNA-Propelled Three-Dimensional DNA Walker for Highly Specific and Rapid Discrimination of Breast Cancer Cell Subtypes in Clinical Tissue Samples

Dual-miRNA-Propelled Three-Dimensional DNA Walker for Highly Specific and Rapid Discrimination of Breast Cancer Cell Subtypes in Clinical Tissue Samples

Abstract 343: New derivatives of 1,3-dioxoisoindoline: Potential breast cancer therapeutics that are S6K1 inhibitors

Abstract Currently, more than 3.8 million women in the United States are diagnosed with breast cancer which is the second leading cause of cancer-related death in women. The correlation of the ribosomal protein S6 kinase 1 (S6K1) activity and breast cancer is evident from the amplification of S6K1 localized chromosomal region 17q23 in 20% of primary breast cancers. S6K1 is a conserved serine/threonine protein kinase, is the principal kinase effector downstream of the PI3K/mTOR regulatory signaling pathway. Over-expression of S6K1 has been associated with cell transformation and elevated proliferation rates in tumors, poor prognosis and an increased risk of local recurrence. S6K1 has been found to play an important role in the progression of ER-positive (ER+) breast cancer, HER2 positive (HER2+) breast cancer and node-negative premenopausal breast cancer. Inhibition of this kinase can prove to be beneficial for the treatment of several types of breast cancer. Our group has identified new molecules that are derivatives of 6-amido-4-aminoisoindoline-1,3-dione core structure as S6K1 inhibitors with low micromolar inhibition potency (IC50 = 2-5 μM). These compounds also inhibited the growth of HER2+ (SKBR3 and HER2Δ16), ER+ and triple negative breast cancer cells (MDA-MB-231 and MDA-MB-468) with a range of EC50 values (2 - 2000 μM). The EC50 values of growth inhibition of these compounds varied by the type of breast cancer cells and were in direct correlation with the expression levels of S6K1 in those cell lines. These results clearly indicate that high efficacy S6K1 inhibitors can function as potential therapeutics for multiple types of breast cancer. Future work involves in-vivo studies to understand the efficacy and pharmacokinetics of the three compounds. Citation Format: Satyendra Kumar, Rajesh Komati, Shahensha Shaik, Melyssa Bratton, Linh Tran, Rion Sam, Elijah Johnson-Henderson, Breyanah Graham, Christopher WIlliams, Jayalakshmi Sridhar. New derivatives of 1,3-dioxoisoindoline: Potential breast cancer therapeutics that are S6K1 inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 343.

Decoding Expression Dynamics of Protein and Transcriptome at the Single-Cell Level in Paired Picoliter Chambers.

Simultaneous analysis of mRNAs and proteins at the single-cell level provides information about the dynamics and correlations of gene and protein expressions in individual cells, enabling a comprehensive study of cellular heterogeneity and expression patterns. Here, we present a platform for about 1000 cellular indexing of mRNAs and membrane proteins, named multi-Paired-seq, with high cell utilization, accurate molecular measurement, and low cost. Based on hydrodynamic differential flow resistance, multi-Paired-seq largely improves cell utilization in the percentage of cells measured in population (>95%). Combined with the pump/valve structure, cell-free antibodies and mRNAs can be removed completely for highly accurate detection (R = 0.96) of protein copies. The picoliter reaction chambers allow high detection sensitivity for both mRNA transcripts and protein copies and low sequencing cost. Using multi-Paired-seq, three clusters of known breast cancer cell types are identified according to multimodal measurements, and the expression correlations between mRNAs and proteins under altered conditions are quantified. Multi-Paired-seq provides multimodal measurements at the single-cell level, which offers a new tool for cell biology, developmental biology, drug discovery, and precision medicine.

Marine-Derived Stichloroside C2 Inhibits Epithelial-Mesenchymal Transition and Induces Apoptosis through the Mitogen-Activated Protein Kinase Signalling Pathway in Triple-Negative Breast Cancer Cells.

Background Triterpenoid saponins from sea cucumbers exhibit significant antitumour, antifungal, and antibacterial activities. However, the associated molecular mechanisms have yet to be elucidated. In this study, we screened and explored the antitumour activity and underlying mechanisms of triterpenoid saponins isolated from Thelenota ananas. Methods We isolated and purified sea cucumber saponins, determined their chemical structures, and confirmed their function in vitro. We also screened and explored the antitumour activity and underlying mechanisms of triterpenoid saponins isolated from Thelenota ananas. Results Four saponins were discovered from sea cucumber Thelenota ananas collected from the South China Sea. We found that stichloroside C2 (STC2) inhibited the proliferation and clonogenesis of the human triple-negative breast cancer (TNBC) cell line MDA-MB-231 and mouse TNBC cell line 4 T1 in a dose-dependent manner and induced apoptosis and cycle arrest in these two TNBC cell lines. STC2 induced DNA damage in two TNBC cell lines and significantly increased the protein expression level of the DNA double-strand break marker γ-H2AX. STC2 downregulated the protein expression levels of phosphorylated cyclin-dependent kinase 1 (CDK1), cyclin B1, CDK2, and cyclin A2 in MDA-MB-231 and 4 T1 cells. STC2 upregulated Bax and cleaved PARP protein expression in two types of breast cancer cells. In addition, STC2 promoted E-cadherin expression; inhibited vimentin expression; upregulated the phosphorylation levels of the mitogen-activated protein kinase (MAPK) signalling pathway-related proteins p38, JNK, and ERK1/2; and downregulated Akt phosphorylation. Conclusions STC2 exerts anti-TNBC activity, inhibits epithelial–mesenchymal transition (EMT), and induces apoptosis by regulating the cell cycle, EMT-related proteins, and MAPK signalling pathway.