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Honokiol and cancer

Ram Prasad, Santosh K Katiyar
Honokiol (C18H18O2) is a biphenolic natural product isolated from the bark and leaves of Magnolia plant spp. During the last decade or more, honokiol has been extensively studied for its beneficial effect against several diseases. Investigations have demonstrated that honokiol possesses anti-carcinogenic, anti-inflammatory, anti-oxidative, anti-angiogenic as well as inhibitory effect on malignant transformation of papillomas to carcinomas in vitro and in vivo animal models without any appreciable toxicity. Honokiol affects multiple signaling pathways, molecular and cellular targets including nuclear factor-κB (NF-κB), STAT3, epidermal growth factor receptor (EGFR), cell survival signaling, cell cycle, cyclooxygenase and other inflammatory mediators, etc...
2016: Advances in Experimental Medicine and Biology
Courey Averett, Arun Bhardwaj, Sumit Arora, Sanjeev K Srivastava, Mohammad Aslam Khan, Aamir Ahmad, Seema Singh, James E Carter, Moh'd Khushman, Ajay P Singh
The poor clinical outcome of pancreatic cancer (PC) is largely attributed to its aggressive nature and refractoriness to currently available therapeutic modalities. We previously reported antitumor efficacy of honokiol (HNK), a phytochemical isolated from various parts of Magnolia plant, against PC cells in short-term in vitro growth assays. Here, we report that HNK reduces plating efficiency and anchorage-independent growth of PC cells and suppresses their migration and invasiveness. Furthermore, significant inhibition of pancreatic tumor growth by HNK is observed in orthotopic mouse model along with complete-blockage of distant metastases...
September 8, 2016: Carcinogenesis
Xiao-Qin Lv, Xin-Ran Qiao, Ling Su, Shu-Zhen Chen
AIM: Honokiol (HNK) is a natural compound isolated from the magnolia plant with numerous pharmacological activities, including inhibiting epithelial-mesenchymal transition (EMT), which has been proposed as an attractive target for anti-tumor drugs to prevent tumor migration. In this study we investigated the effects of HNK on EMT in human NSCLC cells in vitro and the related signaling mechanisms. METHODS: TNF-α (25 ng/mL) in combination with TGF-β1 (5 ng/mL) was used to stimulate EMT of human NSCLC A549 and H460 cells...
September 5, 2016: Acta Pharmacologica Sinica
Jung Min Song, Arunkumar Anandharaj, Pramod Upadhyaya, Ameya R Kirtane, Jong-Hyuk Kim, Kwon Ho Hong, Jayanth Panyam, Fekadu Kassie
Since epidermal growth factor receptor (EGFR) is commonly deregulated in pre-malignant lung epithelium, targeting EGFR may arrest the development of lung cancer. Here, we showed that honokiol (2.5-7.5 μM), a bioactive compound of Magnolia officinalis, differentially suppressed proliferation (up to 93%) and induced apoptosis (up to 61%) of EGFR overexpressing tumorigenic bronchial cells and these effects were paralleled by downregulation of phospho-EGFR, phospho-Akt, phospho-STAT3 and cell cycle-related proteins as early as 6-12 h post-treatment...
July 21, 2016: Oncotarget
Eun-Ryeong Hahm, Krishna Beer Singh, Shivendra V Singh
Honokiol (HNK), a highly promising phytochemical derived from Magnolia officinalis plant, exhibits in vitro and in vivo anticancer activity against prostate cancer but the underlying mechanism is not fully clear. This study was undertaken to delineate the role of c-Myc in anticancer effects of HNK. Exposure of prostate cancer cells to plasma achievable doses of HNK resulted in a marked decrease in levels of total and/or phosphorylated c-Myc protein as well as its mRNA expression. We also observed suppression of c-Myc protein in PC-3 xenografts upon oral HNK administration...
September 2016: Cell Cycle
Jing Pan, Yongik Lee, Yian Wang, Ming You
Cancer continues to be the leading cause of death worldwide. Plants have a long history of use in the treatment of cancer. Honokiol (HNK) is an important bioactive compound found in the bark of Magnolia tree, and has been shown to inhibit cancer growth and metastasis in many cell types in vitro and in animal models. Resistance to chemotherapy and radiotherapy is the major obstacle for cure of cancer. Combination of HNK with many traditional chemotherapeutic drugs as well as radiation sensitizes cancer cells to apoptotic death, suggesting that HNK not only directly inhibits primary cancers and metastasis, but also has potential to overcome drug resistance...
June 2016: Molecular Nutrition & Food Research
Padmamalini Thulasiraman, Andrea Butts Johnson
Understanding the link between chemoresistance and cancer progression may identify future targeted therapy for breast cancer. One of the mechanisms by which chemoresistance is attained in cancer cells is mediated through the expression of multidrug resistance proteins (MRPs). Acquiring drug resistance has been correlated to the emergence of metastasis, accounting for the progression of the disease. One of the diagnostic markers of metastatic progression is the overexpression of a transmembrane protein called Mucin 1 (MUC1) which has been implicated in reduced survival rate...
August 2016: International Journal of Oncology
Courey Averett, Sumit Arora, Haseeb Zubair, Seema Singh, Arun Bhardwaj, Ajay P Singh
Honokiol is a bioactive, biphenolic phytochemical, present in the aerial parts of plants classified under the genus Magnolia. It has been an important constituent of Asian traditional medicine and is used against many ailments. Honokiol possesses potent antioxidative, anti-inflammatory, antiangiogenic, and anticancer activities by targeting a variety of signaling molecules. Consequently, there has been immense interest in exploring its utility as a novel chemopreventive and therapeutic agent against several malignancies...
2014: Enzymes
Jhy-Shrian Huang, Chih-Jung Yao, Shuang-En Chuang, Chi-Tai Yeh, Liang-Ming Lee, Ruei-Ming Chen, Wan-Ju Chao, Jacqueline Whang-Peng, Gi-Ming Lai
BACKGROUND: Eliminating cancer stem cells (CSCs) has been suggested for prevention of tumor recurrence and metastasis. Honokiol, an active compound of Magnolia officinalis, had been proposed to be a potential candidate drug for cancer treatment. We explored its effects on the elimination of oral CSCs both in vitro and in vivo. METHODS: By using the Hoechst side population (SP) technique, CSCs-like SP cells were isolated from human oral squamous cell carcinoma (OSCC) cell lines, SAS and OECM-1...
2016: BMC Cancer
Hongmei Li, Jing Li, Wei Jin, Xing Guo, Nan Li, Tao Ma, Qiang Huo, ChengZhu Wu
OBJECTIVE: To improve the water solubility and biological activity of neoligans (magnolol and honokiol) and test the antitumor activity of the modified compounds. METHODS: The glycosylated products of magnolol and honokiol were obtained by enzymatic synthesis using a UDP-glycosyltransferase (YjiC) from Bacillus. The products were characterized by high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), and nuclear magnetic resonance (NMR) analysis...
November 2015: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Lei Xie, Fuquan Jiang, Xindao Zhang, Gulimiran Alitongbieke, Xinlei Shi, MinJun Meng, Yiming Xu, Anshi Ren, Jing Wang, Lijun Cai, Yunxia Zhou, Yang Xu, Ying Su, Jie Liu, Zhiping Zeng, Guanghui Wang, Hu Zhou, Quan Cheng Chen, Xiao-Kun Zhang
BACKGROUND AND PURPOSE: The orphan nuclear receptor Nur77 is implicated in the survival and apoptosis of cancer cells. The purpose of this study was to determine whether and how Nur77 serves to mediate the effect of the inflammatory cytokine TNF-α in cancer cells and to identify and characterize new agents targeting Nur77 for cancer therapy. EXPERIMENTAL APPROACH: The effects of TNF-α on the expression and function of Nur77 were studied using in vitro and in vivo models...
January 2016: British Journal of Pharmacology
Qing Zhang, Wei Zhao, Changxiao Ye, Junlong Zhuang, Cunjie Chang, Yuying Li, Xiaojing Huang, Lan Shen, Yan Li, Yangyan Cui, Jiannan Song, Bing Shen, Isaac Eliaz, Ruimin Huang, Hao Ying, Hongqian Guo, Jun Yan
The oncoprotein EZH2, as a histone H3K27 methyltransferase, is frequently overexpressed in various cancer types. However, the mechanisms underlying its role in urinary bladder cancer (UBC) cells have not yet fully understood. Herein, we reported that honokiol, a biologically active biphenolic compound isolated from the Magnolia officinalis inhibited human UBC cell proliferation, survival, cancer stemness, migration, and invasion, through downregulation of EZH2 expression level, along with the reductions of MMP9, CD44, Sox2 and the induction of tumor suppressor miR-143...
November 10, 2015: Oncotarget
Laixi Bi, Zhijie Yu, Jianbo Wu, Kang Yu, Guangliang Hong, Zhongqiu Lu, Shenmeng Gao
Constitutive and inducible activation of signal transducer and activator of transcription 3 (STAT3) signaling facilitates the carcinogenesis in most human cancers including acute myeloid leukemia (AML). Negative regulators, such as protein tyrosine phosphatases SHP1, inhibit the activated STAT3 signaling. In this study, we investigated the effect of honokiol (HNK), a constituent of Magnolia officinalis, on the STAT3 signaling. STAT3 signaling and SHP1 expression were measured by quantitative real-time PCR and western blotting in leukemic cell lines and primary AML blasts treated with HNK...
2015: Tohoku Journal of Experimental Medicine
Dimiter B Avtanski, Arumugam Nagalingam, Michael Y Bonner, Jack L Arbiser, Neeraj K Saxena, Dipali Sharma
Leptin, a major adipocytokine produced by adipocytes, is emerging as a key molecule linking obesity with breast cancer therefore, it is important to find effective strategies to antagonize oncogenic effects of leptin to disrupt obesity-cancer axis. Here, we examine the potential of honokiol (HNK), a bioactive polyphenol from Magnolia grandiflora, as a leptin-antagonist and systematically elucidate the underlying mechanisms. HNK inhibits leptin-induced epithelial-mesenchymal-transition (EMT), and mammosphere-formation along with a reduction in the expression of stemness factors, Oct4 and Nanog...
October 6, 2015: Oncotarget
Xiaoqin Lv, Fang Liu, Yue Shang, Shu-Zhen Chen
Honokiol (HNK), a potential antitumor compound, has been widely studied in recent years. It induces apoptosis and affects autophagy in cancer cells, yet the mechanism of its antitumor efficacy remains obscure. Chloroquine (CQ), an autophagy inhibitor, is often applied to sensitize antitumor drugs in clinical trials. Here, we investigated the antitumor effect of HNK or CQ alone or in combination in non-small cell lung cancer (NSCLC) cells. Using an experimental approach, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) or sulforhodamine B (SRB) was used to determine the cytotoxicity of the agents...
September 2015: Oncology Reports
Bin Yan, Zhi-Yong Peng
OBJECTIVE: Gastric carcinoma is a malignant tumor that responds poorly to both chemotherapy and radiation therapy. In our study, we investigated the anti-cancer effect of honokiol, an active component isolated and purified from the Magnolia officinalis, in human gastric carcinoma MGC-803 cell line. METHODS: The cell viability was detected by the CCK8 assay. The cell apoptosis and cell cycle arrest were assessed by flow cytometer. The protein expression of cell cycle regulators and tumor suppressors were analyzed by western blotting...
2015: International Journal of Clinical and Experimental Medicine
Dimiter B Avtanski, Arumugam Nagalingam, Panjamurthy Kuppusamy, Michael Y Bonner, Jack L Arbiser, Neeraj K Saxena, Dipali Sharma
Obesity greatly influences risk, progression and prognosis of breast cancer. As molecular effects of obesity are largely mediated by adipocytokine leptin, finding effective novel strategies to antagonize neoplastic effects of leptin is desirable to disrupt obesity-cancer axis. Present study is designed to test the efficacy of honokiol (HNK), a bioactive polyphenol from Magnolia grandiflora, against oncogenic actions of leptin and systematically elucidate the underlying mechanisms. Our results show that HNK significantly inhibits leptin-induced breast-cancer cell-growth, invasion, migration and leptin-induced breast-tumor-xenograft growth...
June 30, 2015: Oncotarget
Jin Hyoung Cho, Young-Joo Jeon, Seon-Min Park, Jae-Cheon Shin, Tae-Hoon Lee, Seunggon Jung, Hongju Park, Joohyun Ryu, Hanyong Chen, Zigang Dong, Jung-Hyun Shim, Jung-Il Chae
The aim of this study was to investigate anti-inflammatory and anti-cancer effects of honokiol (HK) in two oral squamous cancer cell carcinoma (OSCC) cell lines, HN22 and HSC4, through the regulation of inducible nitric oxide synthase (iNOS) and endoplasmic reticulum resident protein 44 (ERp44). Griess assay, zymography, and quantitative PCR were performed to study iNOS expression and subsequent nitric oxide (NO) production in OSCC cell lines. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomic analysis was used to elucidate the proteins associated with ER stress and cellular cytotoxic response induced by HK...
2015: Biomaterials
Shujie Cheng, Victor Castillo, Isaac Eliaz, Daniel Sliva
Renal cell carcinoma (RCC) is a common urological cancer worldwide and is known to have a high risk of metastasis, which is considered responsible for more than 90% of cancer associated deaths. Honokiol is a small-molecule biphenol isolated from Magnolia spp. bark and has been shown to be a potential anticancer agent involved in multiple facets of signal transduction. In this study, we demonstrated that honokiol inhibited the invasion and colony formation of highly metastatic RCC cell line 786-0 in a dose-dependent manner...
2015: International Journal of Oncology
Tomohiro Nabekura, Takashi Hiroi, Tatsuya Kawasaki, Yuichi Uwai
Drug efflux transporter P-glycoprotein plays an important role in cancer chemotherapy. The nuclear factor-κB (NF-κB) transcription factors play critical roles in development and progression of cancer. In this study, the effects of natural compounds that can inhibit NF-κB activation on the function of P-glycoprotein were investigated using human MDR1 gene-transfected KB/MDR1 cells. The accumulation of daunorubicin or rhodamine 123, fluorescent substrates of P-glycoprotein, in KB/MDR1 cells increased in the presence of caffeic acid phenetyl ester (CAPE), licochalcone A, anacardic acid, celastrol, xanthohumol, magnolol, and honokiol in a concentration-dependent manner...
March 2015: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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