Abstract 260: Apigenin nanoparticle suppresses sphere formation in CD133+/ALDH1high prostate cancer stem cells through downregulation of stem cell markers

Abstract

Abstract The recurrence of prostate cancer after definitive treatment(s) is thought to be due to the potential of rare cancer stem cells (CSCs) to withstand therapy and initiate tumor formation. CSCs are a subpopulation of cancer cells capable of self-renewal and plastic adaptation mediating tumorigenesis, metastasis, and therapy resistance. CSCs are associated with cancer progression and clinical outcome in cancer patients. In the present study, we isolated CSCs from various human prostate cancer 22Rv1, DU145 and PC-3 cells by applying selection of cluster of differentiation 133 cell surface marker and high ALDH1 activity (CD133+/ALDH1high). Next we aimed to identify CD133+/ALDH1high CSCs isolated from human prostate cancer cells and compare their profiles with non-CSCs as bulk counterparts of the population. Subsequently, the CSC population continued to grow in the three-dimensional multicellular spheroids. Differentiation investigated with stem cell-related genomic characteristics exhibited significant increase in genes viz. CD44, Nanog, β-catenin, c-Myc, SOX2 and Oct4 in CSCs at the message level. In further studies we determine the effect of natural plant flavone apigenin on CSC population. Apigenin is abundantly present in common fruits and vegetables and possess remarkable anticancer, anti-angiogenic and anti-metastatic properties. Apigenin loaded polyethylene glycol nanoparticles (Ap-NP) was characterized for particle size, morphology, zeta potential, drug release and encapsulation. Cellular entry and intracellular localization of Ap-NP were assessed by transmission electron microscopy. Treatment of CD133+/ALDH1high CSCs with Ap-NP inhibited cell viability and sphere formation at higher extent in time dependent manner, compared to the non-CSCs counterparts. Furthermore, Ap-NP exposure resulted in the downregulation of Nanog, β-catenin, c-Myc, SOX2 and Oct4 in the CSCs. Taken together, our study demonstrate overexpression of potential CSC markers and the ability to target these CSCs by the use of non-toxic agent apigenin killing this rare population that may lead to the total abolition of tumor recurrence and/or metastasis. Citation Format: Rajnee Kanwal, Sanjeev Shukla, Agata A. Exner, Andreas G. Tzakos, Sanjay Gupta. Apigenin nanoparticle suppresses sphere formation in CD133+/ALDH1high prostate cancer stem cells through downregulation of stem cell markers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 260.