المؤلفون: Manavathi, Bramanandam, Acconcia, Filippo, Rayala, Suresh K., Kumar, Rakesh

المصدر: Proceedings of the National Academy of Sciences of the United States of America, 2006 Oct . 103(43), 15981-15986.

الوصول الحر: https://www.jstor.org/stable/30052091Test

المؤلفون: Ravi, Mathangi, Tentu, Shilpa, Baskar, Ganga, Prasad, Surabhi Rohan, Raghavan, Swetha, Jayaprakash, Prajisha, Jeyakanthan, Jeyaraman, Rayala, Suresh K., Venkatraman, Ganesh, Rohan Prasad, Surabhi

المصدر: BMC Cancer; 10/23/2015, Vol. 15, p1-13, 13p, 1 Diagram, 4 Charts, 7 Graphs

مصطلحات موضوعية: BREAST cancer treatment, ANTINEOPLASTIC agents, CANCER cell culture, PHYCOCYANIN, DNA damage, MITOGEN-activated protein kinases, PROTEIN metabolism, APOPTOSIS, BREAST tumors, CELL cycle, CELL lines, CELL physiology, CELL motility, CELLULAR signal transduction, DRUG therapy, DNA, FLOW cytometry, OXIDOREDUCTASES, WESTERN immunoblotting, PHARMACODYNAMICS

مستخلص: Background: Triple-negative breast cancers represent an important clinical challenge, as these cancers do not respond to conventional endocrine therapies or other available targeted agents. Phycocyanin (PC), a natural, water soluble and non-toxic molecule is shown to have potent anti-cancer property.Methods: In this study, we determined the efficacy of PC as an anti-neoplastic agent in vitro on a series of breast cancer cell lines. We studied effects of PC in inducing DNA damage and apoptosis through western blot and qPCR. Also, anti-metastatic and anti-angiogenic properties were studied by classic wound healing and vasculogenic mimicry assays.Results: We found that triple negative MDA-MB-231 cells were most sensitive to PC (IC50 : 5.98 ± 0.95 μM) as compared to other cells. They also showed decreased cell proliferation and reduced colony formation ability upon treatment with PC. Profile of Cell cycle analysis showed that PC caused G1 arrest which could be attributed to decreased mRNA levels of Cyclin E and CDK-2 and increased p21 levels. Mechanistic studies revealed that PC induced apoptosis as evident by increase in percentage of annexin positive cells, increase in γ-H2AX levels, and by changing the Bcl-2/Bax ratio followed by release of cytochrome C and increased Caspase 9 levels. MDA MB 231 cells treated with PC resulted in decreased cell migration and increased cell adhesive property and also showed anti-angiogenic effects. We also observed that PC suppressed cyclooxygenase-2 (COX-2) expression and prostaglandin E(2) production. All these biological effects of phycocyanin on MDA MB 231 cells could be attributed to decreased MAPK signaling pathway. We also observed that PC is non-toxic to non-malignant cells, platelets and RBC's.Conclusion: Taken together, these findings demonstrate, for the first time, that PC may be a promising anti-neoplastic agent for treatment of triple negative breast cancers. [ABSTRACT FROM AUTHOR]

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المؤلفون: Kanumuri, Rahul^1,2 (AUTHOR), Saravanan, Roshni¹ (AUTHOR), Pavithra, V.³ (AUTHOR), Sundaram, Sandhya³ (AUTHOR), Rayala, Suresh K.^1,2 (AUTHOR) rayala@iitm.ac.in, Venkatraman, Ganesh¹ (AUTHOR) ganeshv@sriramachandra.edu.in

المصدر: Gene. Nov2020, Vol. 760, pN.PAG-N.PAG. 1p.

مصطلحات موضوعية: *BREAST cancer, *BREAST cancer research, *WNT signal transduction, *CELL motility, *ONCOGENES, *MITOSIS

مستخلص: • Breast cancer is a multifaceted disease, which is mainly caused due to deregulations in multiple signalling cascades. • A proteogenomic study on breast (normal/cancer) tissues showed that PAK1 is an outlier kinase which is frequently overexpressed in cancer tissues. • P21 activated kinase (PAK1) is an oncogene which is involved in breast cancer progression by phosphorylation of it's substrates and it is also involved in tamoxifen resistance. • Kinase Interacting Substrate Screening (KISS) methodology can be used to screen subtype specific substrates of PAK1 for identification of druggable targets and biomarkers. Breast cancer is the most frequently diagnosed cancer in women worldwide. Identifying reliable biomarkers and druggable molecular targets pose to be a significant quest in breast cancer research. p21-activated kinase 1 (PAK1) is a serine/threonine kinase that direct cell motility, cytoskeletal remodelling, and has been shown to function as a downstream regulator for various cancer signalling cascades that promote cell proliferation, apoptosis deregulation and hasten mitotic abnormalities, resulting in tumor formation and progression. The heterogeneity and acquired drug resistance are important factors that challenge the treatment of breast cancer. p21-activated kinase 1 signalling is crucial for activation of the Ras/RAF/MEK/ERK, PI3K/Akt/mTOR and Wnt signalling cascades which regulate cell survival, cell cycle progression, differentiation, and proliferation. A study involving proteogenomics analysis on breast cancer tissues showed the PAK1 as outlier kinase. In addition to this, few outlier molecules were identified specific to subtypes of breast cancer. A few substrates of PAK1 in breast cancer are already known. In this paper, we have discussed a similar approach called Kinase Interacting Substrate Screening (KISS) for the identification of novel oncogenic substrates of p21-activated kinase specific to subtypes of breast cancer. Such high throughput approaches are expected to accelerate the process of identifying novel drug targets and biomarkers. [ABSTRACT FROM AUTHOR]