title: Targeting Apoptosis and Multiple Signaling Pathways with Icariside II in Cancer Cells.
abstract: Cancer is the second leading cause of deaths worldwide. Despite concerted efforts to improve the current therapies, the prognosis of cancer remains dismal. Highly selective or specific blocking of only one of the signaling pathways has been associated with limited or sporadic responses. Using targeted agents to inhibit multiple signaling pathways has emerged as a new paradigm for anticancer treatment. Icariside II, a flavonol glycoside, is one of the major components of Traditional Chinese Medicine Herba epimedii and possesses multiple biological and pharmacological properties including anti-inflammatory, anti-osteoporosis, anti-oxidant, anti-aging, and anticancer activities. Recently, the anticancer activity of Icariside II has been extensively investigated. Here, in this review, our aim is to give our perspective on the current status of Icariside II, and discuss its natural sources, anticancer activity, molecular targets and the mechanisms of action with specific emphasis on apoptosis pathways which may help the further design and conduct of preclinical and clinical trials. Icariside II has been found to induce apoptosis in various human cancer cell lines of different origin by targeting multiple signaling pathways including STAT3, PI3K/AKT, MAPK/ERK, COX-2/PGE2 and β-Catenin which are frequently deregulated in cancers, suggesting that this collective activity rather than just a single effect may play an important role in developing Icariside II into a potential lead compound for anticancer therapy. This review suggests that Icariside II provides a novel opportunity for treatment of cancers, but additional investigations and clinical trials are still required to fully understand the mechanism of therapeutic effects to further validate it in anti-tumor therapy.
authors.affiliation: 1. College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Khan
authors.affiliation: 1. College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Amara
authors.initials: A
authors.lastname: Maryam
authors.affiliation: 2. Department of Zoology, University of the Punjab, Quaid-e-Azam Campus, Lahore 54590, Pakistan.
authors.forename: Javed Iqbal
authors.initials: JI
authors.lastname: Qazi
authors.affiliation: 1. College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Tonghui
authors.initials: T
authors.lastname: Ma
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D005419:Flavonoids; C060988:baohuoside I
keywords: Apoptosis; Cancer; Herba epimedii; Icariside II; Multiple signaling pathways