Honokiol causes G0-G1 phase cell cycle arrest in human prostate cancer cells in association with suppression of retinoblastoma protein level/phosphorylation and inhibition of E2F1 transcriptional activity

Hahm, Eun‐Ryeong; Singh, Shivendra V.

doi:10.1158/1535-7163.mct-07-0217

Cited by 104 publications

(99 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results are consistent with those of other reports showing that over 40 mM honokiol decreases the viability of prostate cancer cells but has no effect at 20 mM. 22) The fact that the honokiol treatment at concentrations lower than 20 mM did not cause cell death indicates that the increased expression of ABCA1 due to honokiol is not a cause of cell death.…”

Section: Resultssupporting

confidence: 93%

“…Given that ABCA1 expression is upregulated during apoptosis in human fibroblasts, 21) and honokiol induces apoptosis in tumor cells, 22) we also examined apoptotic processes by TUNEL assay, an indicator of cell death accompanied by DNA fragmentation, in U251-MG cells following the treatment with indicated concentrations (0, 10, 20, 80 mM) of honokiol. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Honokiol Increases ABCA1 Expression Level by Activating Retinoid X Receptor Beta

Jung

Horike

Cha

et al. 2010

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

ABCA1, a member of the ATP-binding cassette transporter family, promotes the efflux of cholesterol and phospholipids from intracellular compartments to extracellular cholesterol acceptors.1) Mutations in the ABCA1 gene result in high-density lipoprotein (HDL) deficiency syndromes, such as Tangier disease, which is characterized by low levels of HDL cholesterol and apolipoprotein A-I (apoA-I) and an increased risk of cardiovascular disease.2,3) ABCA1 also plays an important role in the central nervous system (CNS). Apolipoprotein E (apoE) is one of the major apolipoproteins in CNS, which interacts with ABCA1 4) to remove cholesterol from cells and generates HDL particles in the cerebrospinal fluid.5) The lack of ABCA1 results in a reduction of apoE levels and lipidated apoE-containing lipoproteins in the brain of ABCA1 Ϫ / Ϫ mice.6) It has also been reported that decreased apoE levels and poorly lipidated apoE increase amyloid-b peptide (Ab), a major component of the senile plaque in Alzheimer disease (AD) brains, deposition in ABCA1 Ϫ / Ϫ mice crossed with the AD mouse model. 7) In contrast, overexpression of ABCA1 results in the reduction of Ab deposition through ABCA1-mediated generation of apoE containing lipoproteins in the AD mouse model 8) suggesting that modulation of ABCA1 expression could be a possible therapeutic strategy for AD.ABCA1 is ubiquitously expressed, the expression of which is transcriptionally regulated. The activation of liver X receptor (LXR) by oxysterols and the nonsteriodal synthetic LXR agonist T0901317 increases ABCA1 gene expression level. 9)ABCA1 is also regulated by peroxisome proliferator-activated receptors (PPARs) through their inductive effects on the expression of LXRa.10) Both of these types of receptor form heterodimers with retinoid X receptors (RXRs), 11) and LXR/RXR and PPARs/LXR heterodimers bind to a promoter sequence on the ABCA1 gene. 10,12) In mice models, the synthetic LXR agonist GW3965 increases the plasma HDL cholesterol level and inhibits the development of atherosclerosis, 13) and decrease Ab deposition in the AD mouse model. 14) Although ABCA1 plays an important role in the development of atherosclerosis and pathogenesis of AD, there are relatively few drugs that can upregulate ABCA1 expression. Thus, identification of upregulators of ABCA1 expression may lead to a therapeutic benefit for patients with cardiovascular disease and AD.Because of their simplicity and sensitivity, reporter gene assay systems are used for high-throughput screening (HTS) to identify new compounds for drug development. These strategies offer the advantages of speed, cost-effectiveness, genome coverage, and immediate biological relevance. In the present study, we have developed an HTS method of identifying ABCA1 upregulators, and screened 118 natural compounds using the developed cell-based assay. MATERIALS AND METHODS MaterialsHonokiol and rosiglitazone were purchased from LKT laboratories, Inc. (St. Paul, MN, U.S.A.) and Cayman Chemical (Ann Arbor, MI, U.S.A.), respectively. GW6471,...

show abstract

Section: Resultssupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Honokiol Increases ABCA1 Expression Level by Activating Retinoid X Receptor Beta

Jung

Horike

Cha

et al. 2010

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…We have previously shown that honokiol treatment decreases viability of LNCaP (androgen receptor positive and wild-type p53) and PC-3 (androgen receptor null and p53 null) human prostate cancer cells at 20 to 60 Amol/L concentrations as judged by trypan blue dye exclusion assay (25). In the present study, we used the same cell lines to test whether honokiol promotes apoptosis.…”

Section: Resultsmentioning

confidence: 93%

Honokiol, a Constituent of Oriental Medicinal Herb Magnolia officinalis, Inhibits Growth of PC-3 Xenografts In vivo in Association with Apoptosis Induction

Hahm

Arlotti

Marynowski

et al. 2008

Clinical Cancer Research

Self Cite

View full text Add to dashboard Cite

Purpose: This study was undertaken to determine the efficacy of honokiol, a constituent of oriental medicinal herb Magnolia officinalis, against human prostate cancer cells in culture and in vivo. Experimental Design: Honokiol-mediated apoptosis was assessed by analysis of cytoplasmic histone-associated DNA fragmentation. Knockdown of Bax and Bak proteins was achieved by transient transfection using siRNA. Honokiol was administered by oral gavage to male nude mice s.c. implanted with PC-3 cells. Tumor sections from control and honokiol-treated mice were examined for apoptotic bodies (terminal deoxyribonucleotidyl transferase^mediated dUTP nick end labeling assay), proliferation index (proliferating cell nuclear antigen staining), and neovascularization (CD31 staining). Levels of Bcl-2 family proteins in cell lysates and tumor supernatants were determined by immunoblotting. Results: Exposure of human prostate cancer cells (PC-3, LNCaP, and C4-2) to honokiol resulted in apoptotic DNA fragmentation in a concentration-and time-dependent manner irrespective of their androgen responsiveness or p53 status. Honokiol-induced apoptosis correlated with induction of Bax, Bak, and Bad and a decrease in Bcl-xL and Mcl-1protein levels.Transient transfection of PC-3 cells with Bak-and Bax-targeted siRNAs and Bcl-xL plasmid conferred partial yet significant protection against honokiol-induced apoptosis. Oral gavage of 2 mg honokiol/mouse (thrice a week) significantly retarded growth of PC-3 xenografts without causing weight loss. Tumors from honokiol-treated mice exhibited markedly higher count of apoptotic bodies and reduced proliferation index and neovascularization compared with control tumors. Conclusion: Our data suggest that honokiol, which is used in traditional oriental medicine for the treatment of various ailments, may be an attractive agent for treatment and/or prevention of human prostate cancers.

show abstract

“…In human prostate cancer, honokiol activated p21 (PC-3 and LNCaP) and p53 protein expression (LNCaP; ref. 36).…”

Section: P53 and Its Family Members Pathwaymentioning

confidence: 99%

Targeting Apoptosis Pathways in Cancer and Perspectives with Natural Compounds from Mother Nature

Millimouno

Dong

Liu

et al. 2014

Cancer Prevention Research

234

168

View full text Add to dashboard Cite

Although the incidences are increasing day after day, scientists and researchers taken individually or by research group are trying to fight against cancer by several ways and also by different approaches and techniques. Sesquiterpenes, flavonoids, alkaloids, diterpenoids, and polyphenolic represent a large and diverse group of naturally occurring compounds found in a variety of fruits, vegetables, and medicinal plants with various anticancer properties. In this review, our aim is to give our perspective on the current status of the natural compounds belonging to these groups and discuss their natural sources, their anticancer activity, their molecular targets, and their mechanism of actions with specific emphasis on apoptosis pathways, which may help the further design and conduct of preclinical and clinical trials. Unlike pharmaceutical drugs, the selected natural compounds induce apoptosis by targeting multiple cellular signaling pathways including transcription factors, growth factors, tumor cell survival factors, inflammatory cytokines, protein kinases, and angiogenesis that are frequently deregulated in cancers and suggest that their simultaneous targeting by these compounds could result in efficacious and selective killing of cancer cells. This review suggests that they provide a novel opportunity for treatment of cancer, but clinical trials are still required to further validate them in cancer chemotherapy. Cancer Prev Res; 7(11);

show abstract

Honokiol causes G0-G1 phase cell cycle arrest in human prostate cancer cells in association with suppression of retinoblastoma protein level/phosphorylation and inhibition of E2F1 transcriptional activity

Cited by 104 publications

References 43 publications

Honokiol Increases ABCA1 Expression Level by Activating Retinoid X Receptor Beta

Honokiol Increases ABCA1 Expression Level by Activating Retinoid X Receptor Beta

Honokiol, a Constituent of Oriental Medicinal Herb Magnolia officinalis, Inhibits Growth of PC-3 Xenografts In vivo in Association with Apoptosis Induction

Targeting Apoptosis Pathways in Cancer and Perspectives with Natural Compounds from Mother Nature

Contact Info

Product

Resources

About