Hedgehog/GLI-mediated transcriptional activity inhibitors from Crinum asiaticum

Arai, Midori A.; Akamine, Ryuta; Sadhu, Samir Kumar; Ahmed, Firoj; Ishibashi, Masami

doi:10.1007/s11418-015-0922-8

Cited by 19 publications

(10 citation statements)

References 23 publications

(24 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Smo is released into cytoplasm to activate Gli nuclear translocation, which further initiates target gene transcription [ 23 ]. The transcription of anti-apoptotic factor Bcl2 was shown to be Gli-dependent [ 24 ]. Bcl2 stabilizes the membrane potential of mitochondria to reduce the release of cytochrome C [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Activation of Sonic Hedgehog Signaling Is Associated with Human Osteosarcoma Cells Radioresistance Characterized by Increased Proliferation, Migration, and Invasion

Qü

Wang

et al. 2018

Med Sci Monit

View full text Add to dashboard Cite

BackgroundRadioresistance restricts the application of radiotherapy in human osteosarcoma (OS). This study investigated the molecular mechanism of radioresistance in OS, which may provide clues to finding ideal targets for genetic therapy.Materila/MethodsThe human OS cell line MG63 was employed as parent cells. After repeat low-dose X-ray irradiation of MG63, the radioresistant OS cell line MG63R was produced. Colony formation assay was used to assess the radioresistance. Cell viability was evaluated by CCK-8 assay. Flow cytometry was used to detect cell apoptosis, and wound healing assay was used to evaluate invasive capacity. The nuclear translocation was evaluated by fluorescent immunohistochemistry. Protein expression levels were assessed by Western blotting. Specific siRNA against Shh was used to silence Shh.ResultsMore survival colony formation, elevated cell viability, less cell apoptosis, and increased wound closure were found in MG63R than in MG63 cells exposed to irradiation. The nuclear translocation of Gli, expression levels of Shh, Smo, Ptch1, Bcl2, active MMP2, and active MMP9 were increased in MG63R cells compared with MG63 cells. Transfection of Shh-siRNA suppressed expression levels of Shh, Smo, Ptch1, Bcl2, active MMP2, and active MMP9, as well as the nuclear translocation of Gli in MG63R cells. The cell viability, survival colony formation, and wound closure were impaired, whereas cell apoptosis was increased, in siRNA-transfected MG63R cells than in control MG63R cells exposed to irradiation.ConclusionsActivation of Shh signaling was involved in radioresistance of OS cells. Blocking this signaling can impair the radioresistance capacity of OS cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Activation of Sonic Hedgehog Signaling Is Associated with Human Osteosarcoma Cells Radioresistance Characterized by Increased Proliferation, Migration, and Invasion

Qü

Wang

et al. 2018

Med Sci Monit

View full text Add to dashboard Cite

show abstract

“…The MTT assay was performed in order to estimate the toxicity of free or NC-formulated GlaB. Two different types of cell lines were selected for this study: non-stem cancer cells that contain a small CSC subpopulation (PANC1, human pancreatic carcinoma; SKOV3, human ovary adenocarcinoma; and GL261, murine glioma) [ 41–43 ] and pure glioblastoma-derived neural stem cells (GNS; patient-derived G7 human and engineered Ink4a/ARF, EGFRvIII overexpressed IENS murine) [ 31 ]. It is hypothesized that the GNS cell lines will be more sensitive to GlaB as they consist entirely of CSCs and therefore have a stronger dependence on the Hh pathway.…”

Section: Resultsmentioning

confidence: 99%

Polymeric Glabrescione B Nanocapsules for Passive Targeting of Hedgehog-dependent Tumor Therapy In Vitro

Ingallina

Costa

Ghirga

et al. 2017

Nanomedicine (Lond.)

View full text Add to dashboard Cite

Aim:With the purpose of delivering high doses of glabrescione B (GlaB) to solid tumors after systemic administration, long-circulating GlaB-loaded oil-cored polymeric nanocapsules (NC-GlaB) were formulated.Materials & methods:Synthesis of GlaB and its encapsulation in nanocapsules (NCs) was performed. Empty and GlaB-loaded NCs were assessed for their physico-chemical properties, in vitro cytotoxicity and in vivo biodistribution.Results:GlaB was efficiently loaded into NCs (∽90%), which were small (∽160 nm), homogeneous and stable upon storage. Further, GlaB and NC-GlaB demonstrated specific activities against the cancer stem cells. Preliminary studies in tumor-bearing mice supported the ability of NC to accumulate in pancreatic tumors.Conclusion:This study provides early evidence that NC-GlaB has the potential to be utilized in a preclinical setting and justifies the need to perform therapeutic experiments in mice.

show abstract

“…Several studies have demonstrated that the genus Crinum belonging to the Amaryllidaceae family continue to yield alkaloids having interesting biological activities [ 13 , 30 ]. For example, galanthamine is used for symptomatic treatment of Alzheimer disease [ 31 ], crinine and 6‐ethoxybuphandrine exhibited anticancer effect [ 32 ], and cripowellin A, B, C, and D have antiplasmodial activity [ 33 ]. In the present study, 6-hydroxycrinamine and lycorine have been found in the bulb extract of C. abyscinicum , a plant which is important in Ethiopian traditional medicine [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Antiproliferative Effects of Alkaloids from the Bulbs of Crinum abyscinicum Hochst. ExA. Rich

Abebe

Tadesse

Hymete

et al. 2020

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Crinum abyscinicum Hochst. ExA. Rich bulb is traditionally used in Ethiopia for the treatment of various ailments including internal parasites, mastitis, rabies, colic diseases of animals, and cancer. Despite its importance in traditional cancer treatment, no research work has been reported on the antiproliferative activity of the bulb extract and its major constituents. Phytochemical investigation of the bulb extract of C. abyscinicum by PTLC over silica gel resulted in the isolation of two alkaloids, which were unequivocally identified as 6-hydroxycrinamine and lycorine on the basis of 1H- and 13C-NMR and MS analysis. The bulb extract, 6-hydroxycrinamine, and lycorine possessed significant antiproliferative activity, lycorine being the most active exhibiting GI50 values of 2.8 μg/ml and 3.4 μg/ml against A2780 and MV4-11 cells, respectively. Cell cycle analysis and annexin V/propidium iodide double staining in A2780 cells revealed that both compounds increased the percentage of cells in the S-phase at 30 μg/ml without inducing apoptosis. Our results suggest that the antiproliferative activities of the bulb extract of C. abyscinicum, 6-hydroxycrinamine, and lycorine could support the traditional claim of the plant against cancer.

show abstract

Hedgehog/GLI-mediated transcriptional activity inhibitors from Crinum asiaticum

Cited by 19 publications

References 23 publications

Activation of Sonic Hedgehog Signaling Is Associated with Human Osteosarcoma Cells Radioresistance Characterized by Increased Proliferation, Migration, and Invasion

Activation of Sonic Hedgehog Signaling Is Associated with Human Osteosarcoma Cells Radioresistance Characterized by Increased Proliferation, Migration, and Invasion

Polymeric Glabrescione B Nanocapsules for Passive Targeting of Hedgehog-dependent Tumor Therapy In Vitro

Antiproliferative Effects of Alkaloids from the Bulbs of Crinum abyscinicum Hochst. ExA. Rich

Contact Info

Product

Resources

About