Next Article in Journal
Advances in Cross-Coupling Reactions
Previous Article in Journal
Process Optimization of Ultra-High Molecular Weight Polyethylene/Cellulose Nanofiber Bionanocomposites in Triple Screw Kneading Extruder by Response Surface Methodology
Open AccessArticle

ST09, A Novel Curcumin Derivative, Blocks Cell Migration by Inhibiting Matrix Metalloproteases in Breast Cancer Cells and Inhibits Tumor Progression in EAC Mouse Tumor Models

1
Institute of Bioinformatics and Applied Biotechnology, Electronic city phase 1, Bangalore 560100, India
2
Manipal Academy of Higher Education, Manipal 576104, India
3
Department of Pharmaceutical Chemistry, KLE College of Pharmacy, Rajajinagar, Bangalore, (A Constituent Unit of KLE Academy of Higher Education & Research, Belagavi), Bangalore, KN 5600, India
4
Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysuru 570006, India
5
St. Joseph’s College, Irinjalakuda, Kerala 680661, India
*
Author to whom correspondence should be addressed.
Academic Editor: Qiao-Hong Chen
Molecules 2020, 25(19), 4499; https://doi.org/10.3390/molecules25194499
Received: 5 September 2020 / Revised: 23 September 2020 / Accepted: 25 September 2020 / Published: 30 September 2020
(This article belongs to the Special Issue Anticancer Agents: Design, Synthesis and Evaluation II)
Purpose: Curcumin is known for its anticancer and migrastatic activity in various cancers, including breast cancer. Newer curcumin derivatives are being explored to overcome limitations of curcumin like low bioavailability, stability, and side effects due to its higher dose. In this study, the synthesis of ST09, a novel curcumin derivative, and its antiproliferative, cytotoxic, and migrastatic properties have been explored both in vitro and in vivo. Methods: After ST09 synthesis, anticancer activity was studied by performing standard cytotoxicity assays namely, lactate dehydrogenase (LDH) release assay, 3-(4, 5-dimethylthiazol-2-yl)-2–5-diphenyletrazolium bromide (MTT), and trypan blue exclusion assay. Annexin-FITC, cell cycle analysis using flow cytometry, and Western blotting were performed to elucidate cell death mechanisms. The effect on the inhibition of cell migration was studied by transwell migration assay. An EAC (Ehrlich Ascites carcinoma) induced mouse tumor model was used to study the effect of ST09 on tumor regression. Drug toxicity was measured using aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and flow-cytometry based lymphocyte count. Histological analysis was performed for assessment of any tissue injury post ST09 treatment. Results: ST09 shows an approximate 100-fold higher potency than curcumin, its parent compound, on breast tumor cell lines MCF-7 and MDA-MB231. ST09 arrests the cell cycle in a cell type-specific manner and induces an intrinsic apoptotic pathway both in vitro and in vivo. ST09 inhibits migration by downregulating matrix metalloprotease 1,2 (MMP1,2) and Vimentin. In vivo, ST09 administration led to decreased tumor volume in a mouse allograft model by boosting immunity with no significant drug toxicity. Conclusion: ST09 exhibits antiproliferative and cytotoxic activity at nanomolar concentrations. It induces cell death by activation of the intrinsic pathway of apoptosis both in vitro and in vivo. It also inhibits migration and invasion. This study provides evidence that ST09 can potentially be developed as a novel antitumor drug candidate for highly metastatic and aggressive breast cancer. View Full-Text
Keywords: MDA-MB-231; MCF7; EAC mouse tumor model; apoptosis; migrastatic; immunity boosting cancer therapeutics MDA-MB-231; MCF7; EAC mouse tumor model; apoptosis; migrastatic; immunity boosting cancer therapeutics
Show Figures

Graphical abstract

MDPI and ACS Style

Nirgude, S.; Mahadeva, R.; Koroth, J.; Kumar, S.; Kumar, K.S.S.; Gopalakrishnan, V.; S Karki, S.; Choudhary, B. ST09, A Novel Curcumin Derivative, Blocks Cell Migration by Inhibiting Matrix Metalloproteases in Breast Cancer Cells and Inhibits Tumor Progression in EAC Mouse Tumor Models. Molecules 2020, 25, 4499.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop