title: Molecular Characterization and Enhancement of Anticancer Activity of Caffeic Acid Phenethyl Ester by γ Cyclodextrin.
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 assaysin vitroandin 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.
authors.affiliation: 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.
authors.forename: Renu
authors.initials: R
authors.lastname: Wadhwa
authors.affiliation: 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;; Graduate School of Life & Environmental Sciences, University of Tsukuba, Ibaraki - 305 8575, Japan.
authors.forename: Nupur
authors.initials: N
authors.lastname: Nigam
authors.affiliation: 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;; Graduate School of Life & Environmental Sciences, University of Tsukuba, Ibaraki - 305 8575, Japan.
authors.forename: Priyanshu
authors.initials: P
authors.lastname: Bhargava
authors.affiliation: Department of Biochemical Engineering & Biotechnology, Indian Institute of Technology Delhi, New Delhi - 110 016, India.
authors.forename: Jaspreet Kaur
authors.initials: JK
authors.lastname: Dhanjal
authors.affiliation: School of Biotechnology, Jawaharlal Nehru University, New Delhi - 110 067, India.
authors.forename: Sukriti
authors.initials: S
authors.lastname: Goyal
authors.affiliation: School of Biotechnology, Jawaharlal Nehru University, New Delhi - 110 067, India.
authors.forename: Abhinav
authors.initials: A
authors.lastname: Grover
authors.affiliation: Department of Biochemical Engineering & Biotechnology, Indian Institute of Technology Delhi, New Delhi - 110 016, India.
authors.forename: Durai
authors.initials: D
authors.lastname: Sundar
authors.affiliation: CycloChem Co., Ltd., 7-4-5 Minatojima-minamimachi, Chuo-ku, Kobe - 650 0047, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ishida
authors.affiliation: CycloChem Co., Ltd., 7-4-5 Minatojima-minamimachi, Chuo-ku, Kobe - 650 0047, Japan;; Graduate School of Medicine, Kobe University, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe - 650 0017, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Terao
authors.affiliation: 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.
authors.forename: Sunil C
authors.initials: SC
authors.lastname: Kaul
keywords: CAPE; Propolis; anti-metastasis.; anticancer; complex; p53; upregulation; γCD