scholarly journals Targeting Sonic Hedgehog Signaling by Compounds and Derivatives from Natural Products

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Yu-Chuen Huang ◽  
K. S. Clifford Chao ◽  
Hui-Fen Liao ◽  
Yu-Jen Chen

Cancer stem cells (CSCs) are a major cause of cancer treatment failure, relapse, and drug resistance and are known to be responsible for cancer cell invasion and metastasis. The Sonic hedgehog (Shh) signaling pathway is crucial to embryonic development. Intriguingly, the aberrant activation of the Shh pathway plays critical roles in developing CSCs and leads to angiogenesis, migration, invasion, and metastasis. Natural compounds and chemical structure modified derivatives from complementary and alternative medicine have received increasing attention as cancer chemopreventives, and their antitumor effects have been demonstrated bothin vitroandin vivo. However, reports for their bioactivity against CSCs and specifically targeting Shh signaling remain limited. In this review, we summarize investigations of the compounds cyclopamine, curcumin, epigallocatechin-3-gallate, genistein, resveratrol, zerumbone, norcantharidin, and arsenic trioxide, with a focus on Shh signaling blockade. Given that Shh signaling antagonism has been clinically proven as effective strategy against CSCs, this review may be exploitable for development of novel anticancer agents from complementary and alternative medicine.

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Qiujun Guo ◽  
Jinyin Lin ◽  
Rui Liu ◽  
Yebo Gao ◽  
Shulin He ◽  
...  

Xihuangpill (XH) is a complementary and alternative medicine that has been used in traditional Chinese medicine (TCM) for the treatment of tumors since the 18th century. XH has clinical effects on non-Hodgkin lymphoma, breast cancer, gastric cancer, liver cancer, and bone metastasis. XH can also inhibit the growth of tumor cells and cancer stem cells, prevent tumor invasion and angiogenesis, and regulate the tumor microenvironment. XH is composed ofRu Xiang(olibanum),Mo Yao(Commiphora myrrha),She Xiang(Moschus), andNiu Huang(Calculus bovis). Some of the compounds found in these ingredients exert multiple antitumor effects and may synergize with the other ingredients. We aimed to summarize the clinical applications and molecular mechanisms of XH and its chemical composition. This review will provide potential new strategies and alternative perspectives for tumor treatments and basic research into complementary and alternative medicine.


2011 ◽  
Vol 22 (23) ◽  
pp. 4694-4703 ◽  
Author(s):  
Christine E. Larkins ◽  
Gladys D. Gonzalez Aviles ◽  
Michael P. East ◽  
Richard A. Kahn ◽  
Tamara Caspary

Arl13b, a ciliary protein within the ADP-ribosylation factor family and Ras superfamily of GTPases, is required for ciliary structure but has poorly defined ciliary functions. In this paper, we further characterize the role of Arl13b in cilia by examining mutant cilia in vitro and determining the localization and dynamics of Arl13b within the cilium. Previously, we showed that mice lacking Arl13b have abnormal Sonic hedgehog (Shh) signaling; in this study, we show the dynamics of Shh signaling component localization to the cilium are disrupted in the absence of Arl13b. Significantly, we found Smoothened (Smo) is enriched in Arl13b-null cilia regardless of Shh pathway stimulation, indicating Arl13b regulates the ciliary entry of Smo. Furthermore, our analysis defines a role for Arl13b in regulating the distribution of Smo within the cilium. These results suggest that abnormal Shh signaling in Arl13b mutant embryos may result from defects in protein localization and distribution within the cilium.


2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Jiaxing Feng ◽  
Jing Wang ◽  
Yuehui Zhang ◽  
Yizhuo Zhang ◽  
Liyan Jia ◽  
...  

Female infertility is a state of fertility disorder caused by multiple reasons. The incidence of infertility for females has significantly increased due to various factors such as social pressure, late marriage, and late childbirth, and its harm includes heavy economic burden, psychological shadow, and even marriage failure. Conventional solutions, such as hormone therapy, in vitro fertilization (IVF), and embryo transfer, have the limitations of unsatisfied obstetric outcomes and serious adverse events. Currently, complementary and alternative medicine (CAM), as a new treatment for infertility, is gradually challenging the dominant position of traditional therapies in the treatment of infertility. CAM claims that it can adjust and harmonize the state of the female body from a holistic approach to achieve a better therapeutic effect and has been increasingly used by infertile women. Meanwhile, some controversial issues also appeared; that is, some randomized controlled trials (RCTs) confirmed that CAM had no obvious effect on infertility, and the mechanism of its effect could not reach a consensus. To clarify CAM effectiveness, safety, and mechanism, this paper systematically reviewed the literature about its treatment of female infertility collected from PubMed and CNKI databases and mainly introduced acupuncture, moxibustion, and oral Chinese herbal medicine. In addition, we also briefly summarized psychological intervention, biosimilar electrical stimulation, homeopathy, hyperbaric oxygen therapy, etc.


Author(s):  
Stuart L Jones ◽  
Bruce Campbell ◽  
Tanya Hart

It is increasingly easy for the general public to access a wide range of laboratory tests. Tests can be ordered online with little or no input from a health professional. The complementary and alternative medicine (CAM) community promote and sell a wide range of tests, many of which are of dubious clinical significance. Many have little or no clinical utility and have been widely discredited, whilst others are established tests that are used for unvalidated purposes. They range from the highly complex, employing state of the art technology, e.g. heavy metal analysis using inductively coupled plasma-mass spectrometry, to the rudimentary, e.g. live blood cell analysis. Results of ‘CAM tests’ are often accompanied by extensive clinical interpretations which may recommend, or be used to justify, unnecessary or harmful treatments. There are now a small number of laboratories across the globe that specialize in CAM testing. Some CAM laboratories operate completely outside of any accreditation programme whilst others are fully accredited to the standard of established clinical laboratories. In this review, we explore CAM testing in the United States, the United Kingdom and Australia with a focus on the common tests on offer, how they are reported, the evidence base for their clinical application and the regulations governing their use. We will also review proposed changed to in-vitro diagnostic device regulations and how these might impact on CAM testing.


2018 ◽  
Vol 2018 ◽  
pp. 1-27 ◽  
Author(s):  
Seong-Mok Jeong ◽  
Byung-Kwan Seo ◽  
Yeon-Cheol Park ◽  
Yong-Hyeon Baek

Objective. The objective of this review is to evaluate the recent treatment and study trends of complementary and alternative medicine (CAM) treatments on muscular atrophy by reviewing in vivo/in vitro studies.Materials and Methods. The searches were conducted via electronic databases including PubMed, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang MED, and five Korean databases. Only in vivo and in vitro studies were included in this study.Results. A total of 44 studies (27 in vivo studies, 8 in vitro studies, and 9 in vivo with in vitro) were included. No serious maternal or fetal complications occurred. There were various animal models induced with muscular atrophy through “hindlimb suspension”, “nerve damage”, ‘alcohol or dexamethasone treatment’, “diabetes”, “CKD”, “stroke”, “cancer”, “genetic modification”, etc. In 28 of 36 articles measuring muscle mass, CAM significantly increased the mass. Additionally, 10 of them showed significant improvement in muscle function. In most in vitro studies, significant increases in both the diameter of myotubes and muscle cell numbers were reported. The mechanisms of action of protein synthesis, degradation, autophagy, and apoptotic markers were also investigated.Conclusions. These results demonstrate that CAM could prevent muscular atrophy. Further studies about CAM on muscular atrophy are needed.


2020 ◽  
Author(s):  
CHH Hor ◽  
WY Leong ◽  
ELK Goh

AbstractSonic Hedgehog (Shh) signaling from the primary cilium drives cerebellar granule cell precursor (GCP) proliferation. Mutations of hedgehog (Hh) pathway repressors could cause medulloblastoma, the most prevalent and malignant childhood brain tumor that arises from aberrant GCP proliferation. We demonstrate that brain-specific knockout of a Shh pathway repressor Rab23 in mice caused mis-patterning of cerebellar folia and elevated GCP proliferation during early development, but with no prevalent occurrence of medulloblastoma at adult stage. Strikingly, Rab23-depleted GCPs exhibited up-regulated basal level of Shh pathway activities despite reduced ciliation, and were desensitized against stimulations by Shh and Smoothened (Smo) agonist in primary GCP culture. These results illustrate dual functions of Rab23 in repressing the basal level of Shh signaling, while facilitating Shh signal transduction via Shh/Smo on primary cilium. Collectively, our findings unravel instrumental roles of Rab23 in GCP proliferation and ciliogenesis. Rab23’s potentiation of Shh signaling pathway through the primary cilium and Smo, suggests a potential new therapeutic for Smo/primary cilium-driven medulloblastoma.Author SummaryC.H.H conceived, designed, lead, and performed all in vitro and in vivo experiments, analyzed data and wrote the manuscript. W.Y performed QPCR experiments and primary GCP cultures and analyzed data. E.L.G conceived and directed the study.


2017 ◽  
Vol 3 (6) ◽  
pp. 814-822 ◽  
Author(s):  
Jeffrey D. White ◽  
Hongsheng Lin ◽  
Libin Jia ◽  
Roy S. Wu ◽  
Stephen Lam ◽  
...  

On November 3, 2014, in Bethesda, MD, the Office of Cancer Complementary and Alternative Medicine of the National Cancer Institute held a meeting to examine the potential utility and feasibility of establishing an international consortium for Chinese medicine and cancer. There is significant interest in the West in using components of Chinese medicine (CM) —such as botanicals and herbal medicines, acupuncture and acupressure, and qigong—in the field of oncology, as potential anticancer agents, for symptom management, and to improve quality of life. The proposal for a consortium on CM came from the Chinese Academy of Chinese Medical Sciences, with the aims of improving scientific communications and collaborations and modernizing the studies of CM for cancer. The US National Cancer Institute’s Office of Cancer Complementary and Alternative Medicine agreed to work with Chinese Academy of Chinese Medical Sciences to explore the feasibility of establishing an international consortium for Chinese medicine and cancer. At the meeting, participants from the United States, China, Canada, Australia, and Korea discussed issues in CM and cancer research, treatment, and management, including potential mechanisms of action, proof of efficacy, adverse effects, regulatory issues, and the need for improving the quality of randomized clinical trials of CM treatments and supportive care interventions. Presented in these proceedings are some of the main issues and opportunities discussed by workshop participants.


2012 ◽  
Vol 30 (30_suppl) ◽  
pp. 25-25 ◽  
Author(s):  
Zoya Galcheva-Gargova ◽  
Chia Lin Chu ◽  
Alison Long ◽  
Jay Duffner ◽  
Kimberly Holte ◽  
...  

25 Background: M402 is a novel heparin sulfate mimetic that binds to multiples growth factors, adhesion molecules, and cytokines to inhibit tumor angiogenesis, progression, and metastasis in nonclinical studies. We investigated if M402 could modulate tumor-stroma interactions in pancreatic cancer by inhibiting the Sonic Hedgehog (Shh) pathway as well as inhibit the activity of the extracellular matrix degrading enzyme, heparanase. Methods: Surface plasmon resonance (SPR) was used for analysis of M402 binding to Shh in vitro. A cell based Gli-1 reporter assay was implemented to assess the effect of M402 on Shh signaling. Immunohistochemistry and RT-qPCR were utilized to investigate M402’s effect on Shh activity in an orthotopic Capan-2 model in nude mice. The effect of M402 on heparanase activity in vitro and on Capan-2 tumor samples isolated from treated and untreated mice was measured using an HTRF-FRET assay. Results: There was specific binding of M402 to Shh in vitro. Additionally, Shh signaling was inhibited in the presence of M402. Immunohistochemistry and RT-qPCR of Capan-2 tumor samples from animals treated with M402 also demonstrated reduction of Shh signaling via Gli, its targeted transcription factor. The degree of inhibition of heparanase activity, as measured in the HTRF assay, was affected by the size, structure, and sulfation pattern of the different heparin sulfate mimetics evaluated. M402 was the most potent inhibitor of heparanse activity in vitro from all compounds tested. In addition, treatment with M402 inhibited heparanase activity in the pancreatic tumor lysates in a dose-dependent manner. Conclusions: M402 was shown in nonclinical studies to modulate tumor-stroma interactions involved in the metastatic, invasive, and desmoplastic pathways by simultaneously inhibiting two distinct pathways: Shh signaling and the activity of heparanase. M402 regulates a variety of polysaccharide-based binding proteins, which provides a rationale for the clinical investigation of M402 in a range of cancers.


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