Salinomycin inhibits breast cancer progression via targeting HIF-1α/VEGF mediated tumor angiogenesis in vitro and in vivo.

Published on Jun 1, 2019in Biochemical Pharmacology4.96
· DOI :10.1016/J.BCP.2019.04.026
Jayant Dewangan9
Estimated H-index: 9
(Central Drug Research Institute),
Sonal Srivastava7
Estimated H-index: 7
(Central Drug Research Institute)
+ 3 AuthorsSrikanta Kumar Rath13
Estimated H-index: 13
(Central Drug Research Institute)
Sources
Abstract
Abstract Cancer is a complex disease wherein cells begin to divide abnormally and spread into surrounding tissues. Angiogenesis plays a crucial role in tumor progression as it is required for sustained growth and metastasis, therefore targeting angiogenesis is a promising therapeutic approach for breast cancer management. Salinomycin (SAL) has been reported to exhibit anticancer response on various types of cancer. In the present study, we explored the antiangiogenic and anticancer efficacy of the polyether ionophore SAL in the breast cancer model. It effectively inhibited cell proliferation, invasion, and migration. It also inhibited the expression of pro-angiogenic cell surface marker CD31 in HUVEC, thereby interrupting the endothelial tubulogenesis. It decreased the HIF-1α transcription factor DNA binding activity to HRE sequence in HUVEC and human breast cancer cells. Further, corresponding to our in vitro findings, SAL suppressed neovascularization in the chick chorioallantoic membrane and the Matrigel plug implanted mice model. Bioluminescence and immunofluorescence imaging revealed that SAL treatment in mice inhibits breast cancer growth and tumor angiogenesis. SAL also suppressed the serum VEGFA level in tumor-bearing mice and induced caspase-dependent apoptosis in breast cancer cells. Taken together our findings suggested that SAL inhibits VEGF induced angiogenesis and breast cancer growth via interrupting HIF-1α/VEGF signalling and could be used as a promising antiangiogenic agent for breast cancer treatment.
📖 Papers frequently viewed together
8 Authors (Tao Li, ..., Jing Chen)
25 Citations
11 Citations
2003
5 Authors (Yi Lu, ..., Lisa K. Jennings)
5 Citations
References35
Newest
#1Zonglei Mao (Soochow University (Taiwan))H-Index: 1
#2Yong Wu (Soochow University (Taiwan))H-Index: 1
Last. Chungen Xing (Soochow University (Taiwan))H-Index: 1
view all 4 authors...
: Chemotherapy is the main treatment for advanced gastric cancer. However, the emergence of multidrug resistance (MDR) has become a major obstacle in chemotherapy in many tumors, including gastric cancer. Epithelial-mesenchymal transition (EMT), which is considered an important process in cancer development, also contributes toward tumor MDR. Salinomycin, an EMT blocker, shows broad-spectrum antitumor and chemosensitization properties. Here, we hypothesized that salinomycin could reverse the MDR...
10 CitationsSource
#1Freddie Bray (IARC: International Agency for Research on Cancer)H-Index: 18
#1Freddie Bray (IARC: International Agency for Research on Cancer)H-Index: 119
Last. Ahmedin Jemal (ACS: American Cancer Society)H-Index: 139
view all 6 authors...
This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer...
31.7k CitationsSource
#1Yi Zhao (CQMU: Chongqing Medical University)H-Index: 6
#2Liang Zhong (CQMU: Chongqing Medical University)H-Index: 8
Last. Beizhong Liu (CQMU: Chongqing Medical University)H-Index: 8
view all 11 authors...
: At present, acute promyelocytic leukemia (APL) is the most curable form of acute myeloid leukemia and can be treated using all-trans retinoic acid and arsenic trioxide. However, the current treatment of APL is associated with some issues such as drug toxicity, resistance and relapse. Therefore, other strategies are necessary for APL treatment. In the present study, we investigated the effects of salinomycin (SAL) on APL cell lines NB4 and HL-60 and determined its possible mechanisms. We observ...
9 CitationsSource
#1Jiang Jiang (Dalian Medical University)H-Index: 1
#2Hailong Li (Dalian Medical University)H-Index: 5
Last. Zeyao Tang (Dalian Medical University)H-Index: 19
view all 9 authors...
Since Salinomycin (Sal) emerged its ability to target breast cancer stem cells in 2009, numerous experiments have been carried out to test Sal’s anticancer effects. What deserve to be mentioned is that Sal can efficiently induce proliferation inhibition, cell death and metastasis suppression against human cancers from different origins both in vivo and in vitro without causing serious side effects as the conventional chemotherapeutical drugs on the body. There may be novel cell death pathways in...
29 CitationsSource
#1Jayant Dewangan (Central Drug Research Institute)H-Index: 9
#2Sonal Srivastava (Central Drug Research Institute)H-Index: 7
Last. Srikanta Kumar Rath (Central Drug Research Institute)H-Index: 13
view all 6 authors...
Abstract Human triple-negative breast cancer (TNBC) is poorly diagnosed and unresponsive to conventional hormone therapy. Chetomin (CHET), a fungal metabolite synthesized by Chaetomium cochliodes, has been reported as a promising anticancer and antiangiogenic agent but the complete molecular mechanism of its anticancer potential remains to be elucidated. In our study, we explored the anti-neoplastic action of CHET on TNBC cells. Cytotoxicity studies were performed in human TNBC cells viz. MDA-MB...
11 CitationsSource
#1Jayant Dewangan (Central Drug Research Institute)H-Index: 9
#2Divya Tandon (Central Drug Research Institute)H-Index: 2
Last. Srikanta Kumar Rath (Central Drug Research Institute)H-Index: 13
view all 6 authors...
Resveratrol (RES) is a natural polyphenol having anti-proliferative activity against breast cancer cells. RES in combination with other chemo modulatory agents, minimizes toxicity and increases efficacy of the treatment. Salinomycin (SAL), a monocarboxylic polyether ionophore is known for selectively targeting breast cancer stem cells. Purpose of the present study was to investigate whether RES in combination with SAL exerts synergistic anti-proliferative activity on breast cancer cells. We furt...
27 CitationsSource
#1Kiven Erique Lukong (U of S: University of Saskatchewan)H-Index: 19
Abstract Background Despite a remarkable increase in the depth of our understanding and management of breast cancer in the past 50 years, the disease is still a major public health problem worldwide and poses significant challenges. The palpability of breast tumors has facilitated diagnosis and documentation since ancient times. The earliest descriptions of breast cancer date back to around 3500 BCE. For centuries to follow, theories by Hippocrates (460 BCE) and Galen (200 CE), attributing the c...
77 CitationsSource
#1Jayant Dewangan (Central Drug Research Institute)H-Index: 9
#2Sonal Srivastava (Central Drug Research Institute)H-Index: 7
Last. Srikanta Kumar Rath (Central Drug Research Institute)H-Index: 20
view all 3 authors...
The primary hurdle in the treatment of cancer is acquisition of resistance by the tumor cells toward multiple drugs and selectively targeting the cancer stem cells. This problem was overcome by the chemotherapeutic property of recently discovered drug salinomycin. Exact mechanism of action of salinomycin is not yet known, but there are multiple pathways by which salinomycin inhibits tumor growth. Salinomycin decreases the expression of adenosine triphosphate–binding cassette transporter in multi...
52 CitationsSource
#1Kerri-Ann Norton (Johns Hopkins University)H-Index: 14
#2Aleksander S. Popel (Johns Hopkins University)H-Index: 78
Effects of endothelial cell proliferation and migration rates in a computational model of sprouting angiogenesis
66 CitationsSource
#1Tao LiH-Index: 3
#2Xiaoxia LiuH-Index: 3
Last. Jing Chen (MOE: Chinese Ministry of Education)H-Index: 45
view all 8 authors...
// Tao Li 1, * , Xiaoxia Liu 2, 3, * , Qin Shen 2, 3 , Wenjun Yang 2, 3 , Zhenghao Huo 2, 3 , Qilun Liu 1 , Haiyan Jiao 2, 3 , Jing Chen 2, 3 1 Department of Oncology, General Hospital of the Ningxia Medical University, Yinchuan 750004, China 2 Department of Medical Genetic and Cell Biology, Ningxia Medical University, Yinchuan 750004, China 3 Key Laboratory of Fertility Preservation and Maintenance (Ningxia Medical University), Ministry of Education, Yinchuan 750004, China * These authors contr...
25 CitationsSource
Cited By18
Newest
#1Priyanila Magesh (NITC: National Institute of Technology Calicut)
#2Sanu Thankachan (NITC: National Institute of Technology Calicut)H-Index: 1
Last. Padmanaban S. Suresh (NITC: National Institute of Technology Calicut)H-Index: 7
view all 4 authors...
Abstract null null The breast tumor microenvironment is one of the crucial elements supporting breast cancer tumor progression and metastasis. The fibroblasts are the chief cellular component of the stromal microenvironment and are pathologically activated and differentiated into breast cancer-associated fibroblasts (CAFs). The catabolic phenotype of breast CAFs arises due to metabolic reprogramming of these fibroblasts under pseudo-hypoxic conditions. The metabolic intermediates and ATP produce...
Source
#1Jianhua Zhang (Zhengzhou University)H-Index: 2
#2Bingjian Xue (Zhengzhou University)
Last. Jingruo Li (Zhengzhou University)H-Index: 4
view all 7 authors...
Abstract null null Docosahexaenoic acid (DHA) shows different anti-cancer effects on breast cancer (BC) cell proliferation and progression; however, the underlying molecular mechanism yet still is blanketed in mystery. Herein, we aimed to reveal whether the inhibitory effects of DHA on BC proliferation and migration are exerted, at least in part, through promoting the expression of miR-99a and targeting mTOR signaling. DHA lessened the BC cell viability in a time- and concentration-dependent man...
Source
#2Mahpara Qamar (H.I., S.I.: University of Agriculture, Faisalabad)H-Index: 1
Last. Hafiz M.N. Iqbal (Tec: Monterrey Institute of Technology and Higher Education)H-Index: 63
view all 6 authors...
Abstract null null Characteristics of small group of cancerous cells known as cancer stem cells (CSCs) or tumor initiating cells involve relapse, metastasis, and drug resistant which highly influence the available therapeutic processes. Tumoral drug resistance appears closely related to various acquire or intrinsic characteristics of CSCs e.g., detoxifying enzymes, drug efflux transporters, antiapoptotic protein overexpression, DNA repairability, specific morphology, and quiescence. The specific...
Source
#1Yaping Zhou (Zunyi Medical College)
#2Yao Wan (Zunyi Medical College)
Last. Hui Yao (Zunyi Medical College)
view all 6 authors...
Source
#1Hui Wang (University of Medicine and Health Sciences)
#2Hongyi Zhang (Tongji University)H-Index: 1
Last. Fengfeng Cai (Tongji University)
view all 6 authors...
Breast cancer (BC) is the most frequent cancer among women worldwide and is the leading cause of cancer-related deaths in women. Cancer cells with stem cell-like features and tumor-initiating potential contribute to drug resistance, tumor recurrence, and metastasis. To achieve better clinical outcomes, it is crucial to eradicate both bulk BC cells and breast cancer stem cells (BCSCs). Salinomycin, a monocarboxylic polyether antibiotic isolated from Streptomyces albus, can precisely kill cancer s...
Source
Breast cancer remains one of the leading cancers among women. Cancer stem cells (CSCs) are tumor-initiating cells which drive progression, metastasis, and reoccurrence of the disease. CSCs are resistant to conventional chemo- and radio-therapies and their ability to survive such treatment enables tumor reestablishment. Metastasis is the main cause of mortality in women with breast cancer, thus advances in treatment will depend on therapeutic strategies targeting CSCs. Salinomycin (SAL) is a natu...
Source
#1Ravi Prakash Shukla (Central Drug Research Institute)H-Index: 5
#1Ravi Prakash Shukla (Central Drug Research Institute)H-Index: 5
Last. Prabhat Ranjan MishraH-Index: 30
view all 10 authors...
Angiogenesis driven tumor initiation and progression calls for a targeted therapy. Moreover, combined chemotherapy supplements the therapy to act on the cause of concern. In this study, we aimed to develop a targeted crystalsomes approach to delineate tumor cells against normal cells. Self-assembled crystalline monodispersed nanosized polyethylene-polyethylene glycol (PE-PEG)-based hollow crystalsomes were modified with pluronylated putrescine (Put-PF) and loaded with doxorubicin (Dox), synergis...
1 CitationsSource
#1Guillermo Valdivia (Complutense University of Madrid)H-Index: 1
#2Angela Alonso-Diez (Complutense University of Madrid)H-Index: 3
Last. Laura Peña (Complutense University of Madrid)H-Index: 28
view all 4 authors...
Canine mammary tumors (CMTs) are the most common neoplasm in intact female dogs. Canine mammary cancer (CMC) represents 50% of CMTs and, besides surgery which is the election treatment, additional targeted and non-targeted therapies could offer benefits in terms of survival to these patients. Also, CMC is considered a good spontaneous intermediate animal model for the research of human breast cancer (HBC) and, therefore, the study of new treatments for CMC is a promising field in Comparative Onc...
1 CitationsSource
#1Ana Salomé Correia (University of Porto)H-Index: 1
#2Fátima Gärtner (Institute of Molecular Pathology and Immunology of the University of Porto)H-Index: 33
Last. Nuno Vale (University of Porto)H-Index: 26
view all 3 authors...
Abstract Cancer is a set of extremely complex diseases, which are increasingly prominent today, as it affects and kills millions of people worldwide, being the subject of intense study both in its pathophysiology and therapy. Especially in women, breast cancer is still a cancer with a high incidence and mortality. Even though mortality rates for this type of cancer have declined in recent years, it remains challenging at the treatment level, especially the metastatic type. Due to all the impact ...
Source
#1Qian Zhang (Xiangnan University)H-Index: 1
#2Li Lei (Xiangnan University)H-Index: 1
Last. Di Jing (CSU: Central South University)H-Index: 1
view all 3 authors...
Breast cancer (BC) has a poor prognosis and a high number of visceral metastases. Serine protease inhibitor, clade E member 1 (SERPINE1) is a molecule involved in several human malignancies. However, it remains unknown if SERPINE1 plays a role in the development of taxane resistance in TNBC cells. In the present study, the role and mechanism of SERPINE1 in the development of paclitaxel (PTX) resistance in TNBC cells were investigated. A bioinformatics analysis of gene expression profiles in PTX‑...
2 CitationsSource