Oncotarget

Research Papers:

Depleting ovarian cancer stem cells with calcitriol

Amit Kumar Srivastava, Asim Rizvi, Tiantian Cui, Chunhua Han, Ananya Banerjee, Imrana Naseem, Yanfang Zheng, Altaf A. Wani and Qi-En Wang _

PDF  |  HTML  |  How to cite

Oncotarget. 2018; 9:14481-14491. https://doi.org/10.18632/oncotarget.24520

Metrics: PDF 1622 views  |   HTML 3156 views  |   ?  


Abstract

Amit Kumar Srivastava1,5,*, Asim Rizvi1,2,*, Tiantian Cui1, Chunhua Han1, Ananya Banerjee1,3, Imrana Naseem2, Yanfang Zheng4, Altaf A. Wani1 and Qi-En Wang1

1Department of Radiology, College of Medicine, The Ohio State University, Columbus, OH 43210, USA

2Department of Biochemistry, Faculty of Life Sciences, The Aligarh Muslim University, Aligarh, Uttar Pradesh, 202002, India

3School of Biotechnology, KIIT University, Bhubaneswar, Odisha, 751024, India

4Oncology Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, China

5Current address: Biological Science and Technology Division, CSIR-North East Institute of Science and Technology (CSIR-NEIST), Jorhat, Assam, 785006, India

*These authors have contributed equally to this work

Correspondence to:

Qi-En Wang, email: [email protected]

Keywords: calcitriol; cancer stem cells (CSCs); vitamin D receptor (VDR); Wnt pathway; ovarian cancer

Received: September 25, 2017     Accepted: February 10, 2018     Epub: February 16, 2018    Published: March 06, 2018

ABSTRACT

Cancer stem cells (CSCs) represent the root of many solid tumors including ovarian cancer. Eradication of CSCs represents a novel cancer therapeutic strategy. Calcitriol, also known as 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], is an active metabolite of vitamin D, functioning as a potent steroid hormone. Calcitriol has shown anti-tumor effects in various cancers by regulating multiple signaling pathways. It has been reported that calcitriol can regulate the properties of normal and CSCs. However, the effect of calcitriol on the ovarian cancer growth and ovarian CSCs is still unclear. Here, by using a mouse subcutaneous xenograft model generated with human ovarian cancer cells, we have demonstrated that administration of calcitriol is able to strikingly delay the tumor growth. Calcitriol treatment can also deplete the ovarian CSC population characterized by ALDH+ and CD44+CD117+; decrease their capacity to form sphere under the CSC culture condition, and reduce the frequency of tumor-initiating cells, as evaluated by in vivo limiting dilution analysis. Mechanistic investigation revealed that calcitriol depletes CSCs via the nuclear vitamin D receptor (VDR)-mediated inhibition of the Wnt pathway. Furthermore, the activation of VDR pathway is more sensitive to calcitriol in ovarian CSCs than in non-CSCs, although the expression levels of VDR are comparable. Taken together, our data indicate that calcitriol is able to deplete the ovarian CSC population by inhibiting their Wnt signaling pathway, consequently, impeding the growth of xenograft tumors.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 24520