Abstract 5411: Curcumin nanoformulation: A new therapeutic approach for cervical cancer treatment
Authors: Zaman Mohd Saif , Chauhan Neeraj , Maher Diane M. , Yallapu Murali M. , Jaggi Meena , Chauhan Subhash C. 
Published: May 2015

Background: Cervical cancer is one of the most common and deadly cancers among women worldwide and is associated with persistent Human Papillomavirus (HPV) infection. Currently, Cisplatin based chemo and radio therapy is the best standard treatment for cervical cancer. While screening for cervical cancer can reduce the incidence and mortality, treatment of advanced stage cervical cancer is difficult and often unsuccessful. Resistance to chemo-radio therapy with prolonged treatment, resulting in an invasive form of cancer, requires the development of novel therapeutic modalities to conquer chemo resistance and improve overall life expectancy of patients. Nanotechnology provides targeted delivery of anti-cancer drugs and indicates a new approach for cancer diagnosis and treatment. Our lab has developed PLGA (poly [lactic-co-glycolic acid]), an FDA approved polymer coated nanoparticle(s) using a well-known anti-cancer drug Curcumin (CUR) for the enhanced bioavailability and improved therapeutic efficacy of CUR. Therefore, “we hypothesized that having targeted drug delivery, curcumin nanoparticles (NC) will show improved anti-cancerous effects on cervical cancer cells and will also overcome drug (Cisplatin) resistance when compared with free curcumin.”

Methods: The effect of NC on the proliferation of Caski cervical cancer cells was determined by MTS and colony formation assay. Annexin V/7AAD and propidium iodide (PI) staining was analyzed by flow cytometry to determine NC's effect on apoptosis and cell cycle inhibition, respectively. The expression of apoptotic markers such as poly (ADP-ribose) polymerase (PARP), Caspase 3 and Caspase 9 was determined by immunoblotting. The potential of NC to modulate the expression of miRNAs associated with drug resistance was determined by quantitative RT-PCR. In order to assess efficacy of NC to reduce tumor growth, an orthotopic mouse model was generated using Caski cells stably transfected with fluorescent gene td tomato.

Results: NC effectively inhibited Caski cell growth and also induced apoptosis as determined by staining for Annexin V/7AAD and immunoblotting for cleaved PARP, Caspase 3, and Caspase 9. PI staining clearly revealed that NC treatment arrests growth cycle of Caski cells in the G1- S phase. Additionally, NC treatment caused a marked decrease in the levels of miRNA 21, an oncomiRNA associated with chemoresistance, and enhanced miRNA 214, a tumor suppressor, when compared to free Curcumin. Moreover, NC formulation effectively reduces the tumor burden in athymic nude mice.

Conclusion: Our findings show that PLGA based NC significantly inhibits Caski cervical cancer cell growth and regulates the expression of miRNAs, associated with cervical cancer. In vivo experiments show that NC is efficacious in reducing the tumor burden. Therefore, NC may be a novel chemo-preventive and therapeutic modality for the overall management of cervical cancer.

Citation Format: Mohd Saif Zaman, Neeraj Chauhan, Diane M. Maher, Murali M. Yallapu, Meena Jaggi, Subhash C. Chauhan. Curcumin nanoformulation: A new therapeutic approach for cervical cancer treatment. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5411. doi:10.1158/1538-7445.AM2014-5411