title: Effects of A.marina-Derived Isoquercitrin on TNF-Related Apoptosis-Inducing Ligand Receptor (TRAIL-R) Expression and Apoptosis Induction in Cervical Cancer Cells.
abstract: TNF-related apoptosis-inducing ligand (TRAIL) is an anticancer agent, which has greater apoptosis inducing capacity, but most of the cancer cells become resistant to TRAIL-induced apoptosis. The combined treatment of TRAIL with natural products could restore the cancer cell sensitivity to recombinant human TRAIL (rhTRAIL) protein and might enhance the TNF-related apoptosis-inducing ligand receptor (TRAIL-R) expression. This investigation was aimed to isolate flavonoids from leaves of Avicennia marina and evaluate their potential for sensitization of rhTRAIL in human cervical cancer cells (SiHa). The methanolic extract of A.marina leaves were purified and structure was elucidated as isoquercitrin by NMR and LC-MS analysis. Isolated isoquercitrin showed cytotoxicity against SiHa cell line at IC50of 980 μM. Messenger RNA (mRNA) expression of TRAIL-Rs was quantified by qRT-PCR, combination of isoquercitrin, and/or rhTRAIL increased TRAIL-R1 and TRAIL-R2 gene expression by 7 folds and 4 folds, respectively. Also, FACS assay revealed that combined treatment has increased the early apoptosis up to 7.24%. In the present study, we found that isoquercitrin enhances the mRNA expression of TRAIL-Rs, but the percentage of apoptosis was meager, possibly due to the influence of other anti-apoptotic proteins.
authors.affiliation: Centre of Advanced Study in Marine Biology, Annamalai University, Parangipettai, Tamilnadu, 608502, India.
authors.forename: Sathishkumar
authors.initials: S
authors.lastname: Arumugam
authors.affiliation: Division of Molecular Genetics & Biochemistry, National Institute of Cancer Prevention and Research, I-7, Sector - 39, Noida, Uttar Pradesh, 201 301, India.
authors.forename: Kapil
authors.initials: K
authors.lastname: Bandil
authors.affiliation: Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine University, 40225, Dusseldorf, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Proksch
authors.affiliation: Centre of Advanced Study in Marine Biology, Annamalai University, Parangipettai, Tamilnadu, 608502, India.
authors.forename: Kalaiselvam
authors.initials: K
authors.lastname: Murugiyan
authors.affiliation: Division of Molecular Genetics & Biochemistry, National Institute of Cancer Prevention and Research, I-7, Sector - 39, Noida, Uttar Pradesh, 201 301, India. bharadwajm@icmr.org.in.
authors.forename: Mausumi
authors.identifier: http://orcid.org/0000-0002-5944-8825
authors.initials: M
authors.lastname: Bharadwaj
mesh_terms: D000972:Antineoplastic Agents, Phytogenic; D017209:Apoptosis / Q000187:drug effects*; D032407:Avicennia / Q000737:chemistry*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D018515:Plant Leaves / Q000737:chemistry*; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D009363:Neoplasm Proteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; C016527:isoquercitrin; D011794:Quercetin
keywords: Apoptosis; Isoquercitrin; SiHa; Trail