J Cancer 2016; 7(13):1755-1771. doi:10.7150/jca.15170

Research Paper

Molecular Characterization and Enhancement of Anticancer Activity of Caffeic Acid Phenethyl Ester by γ Cyclodextrin

Renu Wadhwa1, Nupur Nigam1,2, Priyanshu Bhargava1,2, Jaspreet Kaur Dhanjal3, Sukriti Goyal4, Abhinav Grover4, Durai Sundar3, Yoshiyuki Ishida5, Keiji Terao5,6✉, Sunil C Kaul1✉

1. DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), National Institute of Advanced Industrial Science & Technology (AIST), Central 5-41, 1-1-1 Higashi, Tsukuba - 305 8565, Japan;
2. Graduate School of Life & Environmental Sciences, University of Tsukuba, Ibaraki - 305 8575, Japan;
3. Department of Biochemical Engineering & Biotechnology, Indian Institute of Technology Delhi, New Delhi - 110 016, India;
4. School of Biotechnology, Jawaharlal Nehru University, New Delhi - 110 067, India.
5. CycloChem Co., Ltd., 7-4-5 Minatojima-minamimachi, Chuo-ku, Kobe - 650 0047, Japan;
6. Graduate School of Medicine, Kobe University, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe - 650 0017, Japan.

Abstract

Caffeic Acid Phenethyl Ester (CAPE) is a key component in New Zealand propolis, known for a variety of health promoting and therapeutic potentials. We investigated the molecular mechanism of anticancer and anti-metastasis activities of CAPE. cDNA array performed on the control and CAPE-treated breast cancer cells revealed activation of DNA damage signaling involving upregulation of GADD45α and p53 tumor suppressor proteins. Molecular docking analysis revealed that CAPE is capable of disrupting mortalin-p53 complexes. We provide experimental evidence and demonstrate that CAPE induced disruption of mortalin-p53 complexes led to nuclear translocation and activation of p53 resulting in growth arrest in cancer cells. Furthermore, CAPE-treated cells exhibited downregulation of mortalin and several other key regulators of cell migration accountable for its anti-metastasis activity. Of note, we found that whereas CAPE was unstable in the culture medium (as it gets degraded into caffeic acid by secreted esterases), its complex with gamma cyclodextrin (γCD) showed high efficacy in anti-tumor and anti-metastasis assays in vitro and in vivo (when administered through either intraperitoneal or oral route). The data proposes that CAPE-γCD complex is a potent anti-cancer and anti-metastasis reagent.

Keywords: Propolis, CAPE, γCD, complex, upregulation, p53, anticancer, anti-metastasis.

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How to cite this article:
Wadhwa R, Nigam N, Bhargava P, Dhanjal JK, Goyal S, Grover A, Sundar D, Ishida Y, Terao K, Kaul SC. Molecular Characterization and Enhancement of Anticancer Activity of Caffeic Acid Phenethyl Ester by γ Cyclodextrin. J Cancer 2016; 7(13):1755-1771. doi:10.7150/jca.15170. Available from http://www.jcancer.org/v07p1755.htm