Phospholipidated curcumin inhibits cell growth of cervical cancer cells via modulation of wnt pathway

Shadi Khorrami,1,* Shadi khorrami,2 Shima alinasab,3 Mehrdad moetamani-ahmadi,4 Amirhossein sahebkar,5 Fatemeh daneshmand,6

1. Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
2. Cancer Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
3. 1) Department of Biology, Payame Noor University, Taft, Islamic Republic of Iran
4. 3) Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran.
5. 4) Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
6. 1) Department of Biology, Payame Noor University, Taft, Islamic Republic of Iran

Abstract

Introduction

Cervical cancer is the fourth leading causes of cancer death among women, and it is most notable in developing countries. despite improvement in the treatment approaches including surgery, radiation, and chemotherapy the prognosis of cervical cancer remains unfavorable. therefore it is needed to identify new anticancer agents to increase the efficacy of current treatment modalities in cervical cancer. curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), which is one of the basic materials derived from turmeric and the rhizome of curcuma longa (l), is generally used as dietary pigment as well as food additive. different studies suggest that curcumin has anti-cancerous, anti-inflammatory and anti-oxidant attributes. clinical studies demonstrated that curcumin is safe enough for humans, as it can be used at high doses, but its disadvantage is its very low bioavailability that lead to limited therapeutic usage. curcumin can induce apoptosis in tumor cells and is potential for anti-angiogenesis which lead to cancer suppression. curcumin anticancer action consists inhibition of the stat3 and nf-κb signaling pathways as the important molecular mechanisms in cancer development and progression. cervical cancer as the curcumin anticancer target is investigated in following article. the cervical cancers are classified into two types according to the pathology: squamous cell carcinoma (80% of cases) and adenocarcinoma (10 to curcumin increasingly mediates anti-proliferative effects owning to various pathways including,cyclooxygenase-2 (cox-2), β-catenin, forkhead box o3 (foxo3), transcription factors such as hif-1a and nf-kb, protein kinase b (akt), cyclin d1 expression and etc. in this study, we investigated the inhibitory activity of curcumin on nf-kb and wnt/β-catenin pathway in cervical cancer cell line.

Methods

The antiproliferative activity of phospholipidated curcumin was assessed in monolayer and spheroid models. the influence of the cell cycle and expression levels of cyclind1 and survivin was assessed by facs and rt-pcr, respectively.

Results

Phospholipidated curcumin suppressed cell growth in hella cells. this novel form of curcumin inhibits tumor spheroids and increased apoptosis. moreover we found that curcumin was able to reduce the expression of cyclind1 and surviving, while increased the level of e-cadherin.

Conclusion

Our finding demonstrated the therapeutic potential of novel phospholipidated curcumin in cervical cancers cells, suggesting further investigations on the therapeutic application of this agent in in vivo models.

Keywords

Cervical cancers, curcumin, anti-tumor effect, spheroid