Triple negative breast cancer in Asia: An insider’s view

Wang, Chao; Kar, Shreya; Lai, Xianning; Cai, Wanpei; Arfuso, Frank; Sethi, Gautam; Lobie, Peter E.; Goh, Boon Cher; Lim, Lina H.K.; Hartman, Mikael; Chan, Ching Wan; Lee, Soo C.; Tan, S. G.; Kumar, Alan Prem

doi:10.1016/j.ctrv.2017.10.014

Cited by 159 publications

(121 citation statements)

References 97 publications

Supporting

Mentioning

119

Contrasting

Unclassified

Order By: Relevance

“…We noted several metabolites as novel in our study, including N-acetyl-L-histidine, phosphatidylinositol (PIP), phosphatidylinositol (PI), and dehydroascorbic acid. These metabolic signatures could be sourced from the unique genetic, lifestyle, and other environmental factors, leading to the unique TNBC phenotype in Asian females, such as being diagnosed at a younger age of 40-50 and more aggressive disease behavior 16 . Therefore, these unique metabolic signatures could potentially be used to further investigate the intriguing mechanism of race-specific TNBC phenotypes and disease outcome.…”

Section: Discussionmentioning

confidence: 99%

Metabolomics-Based Discovery of Molecular Signatures for Triple Negative Breast Cancer in Asian Female Population

Zheng

Zhou

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Triple negative breast cancer (TNBC) is a devastating cancer disease characterized by its poor prognosis, distinct metastatic patterns, and aggressive biological behavior. Research indicates that the prevalence and presentation of TNBC varies among races, with Asian TNBC patients more commonly presenting with large invasive tumors, high node positivity, and high histologic grade. In this work, we applied ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS)based metabolomics to discover metabolic signatures in Asian female TNBC patients. Serum samples from 31 TNBC patients and 31 healthy controls (CN) were involved in this study. A total of 2860 metabolic features were detected in the serum samples. Among them, 77 metabolites, whose levels were significantly different between TNBC with CN, were confirmed. Using multivariate statistical analysis, literature mining, metabolic network and pathway analysis, we performed an in-depth study of the metabolic alterations in the Asian TNBC population. In addition, we discovered a panel of metabolic signatures that are highly correlated with the 5-year survival rate of the TNBC patients. this metabolomic study provides a better understanding of the metabolic details of tnBc in the Asian population. Among women, breast cancer (BC) is the most common type of cancer and also the 2 nd leading cause of death worldwide 1. BC can be divided into several major subtypes based on conventional immunohistochemistry detection of hormone receptors, including human estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth receptor-2 (HER2). As a highly heterogeneous disease, patients with BC have various morphological spectrum, clinical presentation, and prognostic outcomes 2. Among the various subtypes, triple negative breast cancer (TNBC) uniquely lacks expression of all three hormone receptors and accounts for 15-20% of the BC cases. TNBC has attracted more attention compared with other BC subtypes as it is typically associated with high aggression, poor prognosis and a high risk of disease relapse within 5 years following diagnosis 3. Women with TNBC have a high frequency of metastasis to the lung, liver and brain, and survival is generally poor. Another troubling feature associated with the disease is the disparity of presentation and survival compared with other ethnicities 4-9. It is thus of great demand to study the molecular basis of TNBC in order to guide the development of promising drugs and therapies for treatment. Metabolomics is an emerging technology for health science research, representing a more recent addition to the suite of "omics" tools. In particular, mass spectrometry (MS)-based metabolomic analysis enables the most comprehensive measurement of metabolites in a given biological system. It is thus a powerful analytical tool to identify metabolic biomarkers associated with disease or abnormal phenotypes for clinical applications 4. Since metabolites are the end products of gene regulatory processes and prote...

show abstract

Section: Discussionmentioning

confidence: 99%

Metabolomics-Based Discovery of Molecular Signatures for Triple Negative Breast Cancer in Asian Female Population

Zheng

Zhou

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…In this work, we tested the cytotoxic activity of Ilamycin C in TNBC cell lines (MDA-MB-231 and BT-549), non-TNBC cell line (MCF7), and normal breast epithelial cell line (MCF10A) . Doxorubicin and cisplatin are the traditional clinical chemotherapy drugs for TNBC [43]. Interestingly, compared with doxorubicin and cisplatin, the IC 50 values revealed that the cytotoxic activity of Ilamycin C is more specific to TNBC cells than non-TNBC MCF7 and nonmalignant MCF10A cells, implying Ilamycin C may play a selective inhibitory role in TNBC, implying Ilamycin C has potential to serve as a novel clinical chemotherapy drug for the treatment of TNBC.…”

Section: Discussionmentioning

confidence: 99%

Ilamycin C induces apoptosis and inhibits migration and invasion in triple-negative breast cancer by suppressing IL-6/STAT3 pathway

et al. 2019

View full text Add to dashboard Cite

Background: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with poor prognosis, and its treatment remains a challenge due to few targeted medicines and high risk of relapse, metastasis, and drug resistance. Thus, more effective drugs and new regimens for the therapy of TNBC are urgently needed. Ilamycins are a kind of cyclic peptides and produced by Streptomyces atratus and Streptomyces islandicus with effective anti-tuberculosis activity. Ilamycin C is a novel compound isolated from the deep South China Seaderived Streptomyces atratus SCSIO ZH16 and exhibited a strong cytotoxic activity against several cancers including breast cancer cell line MCF7. However, the cytotoxic activity of Ilamycin C to TNBC cells and a detailed antitumor mechanism have not been reported. Methods: CCK-8 assays were used to examine cell viability and cytotoxic activity of Ilamycin C to TNBC, non-TNBC MCF7, and nonmalignant MCF10A cells. EdU assays and flow cytometry were performed to assess cell proliferation and cell apoptosis. Transwell migration and Matrigel invasion assays were utilized to assess the migratory and invading capacity of TNBC cells following the treatment of Ilamycin C. The expressions of proteins were detected by western blot. Results: In this study, we found that Ilamycin C has more preferential cytotoxicity in TNBC cells than non-TNBC MCF7 and nonmalignant MCF10A cells. Notably, our studies revealed the mechanism that Ilamycin C can induce Bax/Bcl-2-related caspase-dependent apoptosis and inhibit migration and invasion through MMP2/MMP9/vimentin/ fascin in TNBC by suppressing IL-6-induced STAT3 phosphorylation. Conclusions: This study provides the first evidence that Ilamycin C has significant implications for the potential as a novel IL-6/STAT3 inhibitor for TNBC treatment in the future.

show abstract

“…Cancer denotes an assembly of diseases that share a collective overall phenotype, irrepressible cell progression, and proliferation which can affect any organ in humans (1). Cancer is the most prominent cause of death worldwide, with 1.7 million new cases per annum, and is likely to extend to 26 million by 2030 (2). Among all the cancers, breast cancer, and lung cancer are the most affected parts and are known to be malicious diseases in the world (3).…”

Section: Introductionmentioning

confidence: 99%

Strophanthidin Attenuates MAPK, PI3K/AKT/mTOR, and Wnt/β-Catenin Signaling Pathways in Human Cancers

2020

View full text Add to dashboard Cite

Lung cancer is the most prevalent in cancer-related deaths, while breast carcinoma is the second most dominant cancer in women, accounting for the most number of deaths worldwide. Cancers are heterogeneous diseases that consist of several subtypes based on the presence or absence of hormone receptors and human epidermal growth factor receptor 2. Several drugs have been developed targeting cancer biomarkers; nonetheless, their efficiency are not adequate due to the high reemergence rate of cancers and fundamental or acquired resistance toward such drugs, which leads to partial therapeutic possibilities. Recent studies on cardiac glycosides (CGs) positioned them as potent cytotoxic agents that target multiple pathways to initiate apoptosis and autophagic cell death in many cancers. In the present study, our aim is to identify the anticancer activity of a naturally available CG (strophanthidin) in human breast (MCF-7), lung (A549), and liver cancer (HepG2) cells. Our results demonstrate a dose-dependent cytotoxic effect of strophanthidin in MCF-7, A549, and HepG2 cells, which was further supported by DNA damage on drug treatment. Strophanthidin arrested the cell cycle at the G2/M phase; this effect was further validated by checking the inhibited expressions of checkpoint and cyclin-dependent kinases in strophanthidin-induced cells. Moreover, strophanthidin inhibited the expression of several key proteins such as MEK1, PI3K, AKT, mTOR, Gsk3α, and β-catenin from MAPK, PI3K/AKT/mTOR, and Wnt/β-catenin signaling. The current study adequately exhibits the role of strophanthidin in modulating the expression of various key proteins involved in cell cycle arrest, apoptosis, and autophagic cell death. Our in silico studies revealed that strophanthidin can interact with several key proteins from various pathways. Taken together, this study demonstrates the viability of strophanthidin as a promising anticancer agent, which may serve as a new anticancer drug.

show abstract

Triple negative breast cancer in Asia: An insider’s view

Cited by 159 publications

References 97 publications

Metabolomics-Based Discovery of Molecular Signatures for Triple Negative Breast Cancer in Asian Female Population

Metabolomics-Based Discovery of Molecular Signatures for Triple Negative Breast Cancer in Asian Female Population

Ilamycin C induces apoptosis and inhibits migration and invasion in triple-negative breast cancer by suppressing IL-6/STAT3 pathway

Strophanthidin Attenuates MAPK, PI3K/AKT/mTOR, and Wnt/β-Catenin Signaling Pathways in Human Cancers

Contact Info

Product

Resources

About