title: Novel quercetin derivative TEF induces ER stress and mitochondria-mediated apoptosis in human colon cancer HCT-116 cells.
abstract: Although quercetin is very well known for its anticancer activity, however it shows some drawbacks. Herein, we have evaluated the apoptotic effect TEF (5, 3'-dihydroxy-3, 7, 4'-triethoxyflavone), a newly synthesized quercetin derivative on HCT-116 colon cancer cells. After 24h of treatment, the proliferation of colon cancer cells was inhibited by TEF. TEF induced apoptosis, as confirmed by the presence of fragmented nuclei, reduced mitochondrial membrane potential, and elevated cytoplasmic and mitochondrial reactive oxygen species (ROS) levels. TEF treatment causes elevation of IRE1-α and activates calcium ions (Ca2+) with concomitant increase in JNK levels. Elevated Ca2+ion translocates from ER to mitochondria which leads to ROS release and oxidative stress. TEF treatment further elevated levels of pro-apoptotic factors and down-regulated the level of Bcl2. TEF led to activation of mito-JNK (mitochondrial JNK), which plays a crucial role in activation of oxidative stress and caspase mediated apoptotic cell death. Moreover, JNK inhibition shown to suppress TEF induced apoptosis in HCT-116 colon cancer cells. Therefore, this study reveals the apoptotic role of TEF against HCT-116 cell line via IRE1-α and mito-JNK pathway.
authors.affiliation: Department of Biotechnology, Daegu University, Gyeongsan, Gyeongbuk 38453, Republic of Korea.
authors.forename: Imran
authors.initials: I
authors.lastname: Khan
authors.affiliation: Department of Biotechnology, Daegu University, Gyeongsan, Gyeongbuk 38453, Republic of Korea.
authors.forename: Souren
authors.initials: S
authors.lastname: Paul
authors.affiliation: Department of Biotechnology, Daegu University, Gyeongsan, Gyeongbuk 38453, Republic of Korea.
authors.forename: Rekha
authors.initials: R
authors.lastname: Jakhar
authors.affiliation: Department of Biotechnology, Daegu University, Gyeongsan, Gyeongbuk 38453, Republic of Korea.
authors.forename: Monika
authors.initials: M
authors.lastname: Bhardwaj
authors.affiliation: Metalloenzyme Research Group and Department of Integrative Plant Science, Chung-Ang University, Anseong 456-756, Republic of Korea.
authors.forename: Jaehong
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Biotechnology, Daegu University, Gyeongsan, Gyeongbuk 38453, Republic of Korea. Electronic address: sckang@daegu.ac.kr.
authors.forename: Sun Chul
authors.initials: SC
authors.lastname: Kang
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000502:physiology*; D045325:HCT116 Cells; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012821:Silanes / Q000737:chemistry / Q000494:pharmacology
chemical_list: D017382:Reactive Oxygen Species; D012821:Silanes; C533587:triethoxyfluorosilane; D011794:Quercetin
keywords: Apoptosis; Mitochondria; Quercetin; TEF