Review The Chinese herb Magnolia officinalis is widely used as a folk remedy for gastrointestinal dis- orders, cough, anxiety and allergic diseases in South Korea, China and Japan [1] . Magnolia bark is rich in two biphenolic compounds, honokiol (3,5-di-[2-propenyl]-1,1-biphenyl-2,2-diol) and its isomer magnolol (FiguRe 1) . Honokiol (1) dif- fers from magnolol (2) in the relative arrange- ment of one of its hydroxyl groups with respect to allyl groups, in the phenolic ring, and is the most important bioactive constituent within the Magnolia genus [2] . In recent studies, honokiol has been found to have anti-angiogenic [3] , anti- cancer [4] , anti-inflammatory [5] , neuroprotective [6] and GABA modulating [7] properties in vitro and in preclinical models. Honokiol and its ana- logs target multiple signaling pathways includ- ing NF- κB [8,9] , signal transducers and activa- tor of transcription 3 (STAT3) [10] , EGFR [11] , mammalian target of rapamycin (m-TOR) [12] and caspase-mediated apoptosis pathway [13] , which regulate cancer initiation and progression. Several studies have demonstrated that honokiol possesses cytotoxic activity against several cancer cell lines (Box 1) [3,10,13–27] . Mechanism of action of honokiol  Inhibition of NF-kB pathway & NF-kB–STAT3 interaction The NF-kB pathway is the most important cellular signal transduction pathway involved in immunity, inflammation, proliferation and defence against apoptosis. It was first described by Sen and Baltimore as a ubiquitous nuclear transcription factor binding to the kappa immunoglobulin-light chain enhancer and subsequently shown to be a regulator in the development of cancer [28] . NF-kB regulates the expression of cytokines, inducible NOS, COX-2, growth factors, inhibitors of apoptosis and effector enzymes in response to ligation of many receptors involved in immunity including T-cell receptors, B-cell receptors and members of the Toll-like receptor/IL-1 receptor super fam- ily [29] . The stimuli, such as TNF- a, lipopoly- saccharides or phorbol-12-myristate-13-acetate activate NF-kB. Activation of NF-kB results in the expression of genes such as Bcl-2, Bcl-xL, XIAP, c-IAP1 and c-IAP2 that are responsible for the inhibition of apoptosis [30,31] . The classic form of NF-kB is the heterodimer of the p50 and p65 subunits, which contains the transcrip- tional activation domain and is sequestered in the cytoplasm, as an inactive complex, by the inhibitory proteins IkBs [32] . Honokiol activates IKKs, which, in turn, phosphorylate two key serine residues, Ser32 and Ser36, on IkBs within the N-terminal response domain. Phosphory- lated IkBs then undergo ubiquitination and pro- teolysis by the 26S proteosome, and the release of IkBs unmasks the nuclear localization signal, which results in translocation of NF-kB to the nucleus, followed by the activation of specific anti-apoptotic genes [9] . Honokiol inhibits TNF- a induced NF-kB activation, IkB a phosphorylation, IkB a deg- radation and RANKL-mediated NF-kB acti- vation, as well as inhibits NF-kB-dependent reporter gene expression induced by TNF- a, TRADD, TRAF, NIK and IKKb. The Honokiol analogs: a novel class of anticancer agents targeting cell signaling pathways and other bioactivities Honokiol (3,5-di-(2-propenyl)-1,1-biphenyl-2,2-diol) is a natural bioactive neolignan isolated from the genus Magnolia. In recent studies, honokiol has been observed to have anti-angiogenic, anticancer, anti-inflammatory, neuroprotective and GABA-modulating properties in vitro and in preclinical models. Honokiol and its analogs target multiple signaling pathways including NF-kB, STAT3, EGFR, mTOR and caspase-mediated common pathway, which regulate cancer initiation and progression. Honokiol and its targets of action may be helpful in the development of effective analogs and targeted cancer therapy. In this review, recent data describing the molecular targets of honokiol and its analogs with anticancer and some other bioactivities are discussed. Ankit Kumar*, Umesh Kumar Singh & Anurag Chaudhary Kharvel Subharti College of Pharmacy, Swami Vivekanand Subharti University, NH-58, Meerut Bypass Road, Meerut – 250005, India *Author for correspondence: Tel.: +919897270453 E-mail: ankit_manipal07@yahoo.co.in 809 ISSN 1756-8919 10.4155/FMC.13.32 © 2013 Future Science Ltd Future Med. Chem. (2013) 5(7), 809–829 For reprint orders, please contact reprints@future-science.com