Chitosan Induces Apoptosis via Caspase‐3 Activation in Bladder Tumor Cells

Hasegawa, Masamitsu; Yagi, Kazuichi; Iwakawa, Seigo; Hirai, Midori

doi:10.1111/j.1349-7006.2001.tb01116.x

Cited by 145 publications

(90 citation statements)

References 32 publications

(39 reference statements)

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“…Also, in this study insulin-free nanospheres had a slight hypoglycemic effect probably because many viscous soluble polysaccharides have been correlated with hypocholesterolemic and hypoglycaemic effects (Burting 2003) and this may be the case of alginate (Ohta et al 1997). Chitosan also has been used as a hypocholesterolemic and hypoglycaemic agent (Hasegawa et al 2001) and may be responsible for hypoglycemic effect observed in diabetic rats. Finally, hydrated nanospheres showed a much stronger hypoglycemic effect than did dehydrated nanospheres, likely due to differences in insulin absorption.…”

Section: Discussionmentioning

confidence: 99%

Polyelectrolyte Biomaterial Interactions Provide Nanoparticulate Carrier for Oral Insulin Delivery

et al. 2008

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Section: Discussionmentioning

confidence: 99%

Polyelectrolyte Biomaterial Interactions Provide Nanoparticulate Carrier for Oral Insulin Delivery

et al. 2008

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“…For instance, its lipoic acid component, has been shown to inhibit cell proliferation and growth, as well as induce the selective apoptosis of a number of cancer cell lines (through the downregulation of the BCL-2 protein), including lung cancer cells (Choi et al, 2009;Dozio et al, 2010;Michikoshi et al, 2013;Moungjaroen et al, 2006;Na et al, 2009;Wenzel et al, 2005). Furthermore, previous studies have also shown that chitosan inhibits cell proliferation and metastases, as well as induces apoptosis (Hasegawa et al, 2001;Kim et al, 2013). The cationic nature of LACPEG could also enhance the cellular uptake of the carrier (Peetla et al, 2014), which could, in turn, increase these effects.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Mixed micelles of lipoic acid-chitosan-poly(ethylene glycol) and distearoylphosphatidylethanolamine-poly(ethylene glycol) for tumor delivery

Elsaid¹,

Taylor²,

Puri

et al. 2017

European Journal of Pharmaceutical Sciences

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Mixed micelles of lipoic acidchitosan-poly(ethylene glycol) and distearoylphosphatidylethanolamine-poly(ethylene glycol) for tumor delivery. The address for the corresponding author was captured as affiliation for all authors. Please check if appropriate. Phasci(2017Phasci( ), doi: 10.1016Phasci( / j.ejps.2017 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T 2 AbstractMany chemotherapeutics suffer from poor aqueous solubility and tissue selectivity.Distearoylphosphatidylethanolamine-poly(ethylene glycol) (DSPE-PEG) micelles are a promising formulation strategy for the delivery of hydrophobic anticancer drugs. However, storage and in vivo instability restrict their use. The aim of this study was to prepare mixed micelles, containing a novel polymer, lipoic acid-chitosan-poly(ethylene glycol) (LACPEG), and DSPE-PEG, to overcome these limitations and potentially increase cancer cell internalisation. Drug-loaded micelles were prepared with a model tyrosine kinase inhibitor and characterized for size, surface charge, stability, morphology, drug

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“…Briefly, the anticancer properties of chitosan have been explained by an antiproliferative action in human gastric carcinoma cell line MGC803 cell [19], as well as in some human breast cancer cell lines [20] or in a human monocytic leukemia cell line, THP-1 [21]; by a necrotic action in various tumor cell lines [19,[22][23]; or by an apoptotic effect in several other cancer cell lines [24][25]. More specifically, Takimoto et al showed that chitosan induced apoptosis by modulating death receptor expression and activating caspase-8 on human bladder tumor cells [25] while Hasegawa et al demonstrated that chitosan induced apoptotic death of bladder tumor cells via caspase-3 activation [24]. On the other hand, Qi et al demonstrated that an antitumor mechanism induced by chitosan in human hepatocellular carcinoma was mediated by the neutralization of cell surface charge, decrease of mitochondrial membrane potential and induction of membrane lipid peroxidation [26].…”

Section: Introductionmentioning

confidence: 99%

Anticancer properties of chitosan on human melanoma are cell line dependent

Gibot

Chabaud

Bouhout

et al. 2015

International Journal of Biological Macromolecules

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Purpose: Chitosan, a natural macromolecule, is widely used in medical and pharmaceutical fields because of its distinctive properties such as bactericide, fungicide and above all its antitumor effects. Although its antitumor activity against different types of cancer had been previously described, its mechanism of action was not fully understood. Materials and Methods: Coating of chitosan has been used in cell cultures with A375, SKMEL28 and RPMI7951 cell lines. Adherence, proliferation and apoptosis were investigated. Results: Our results revealed that whereas chitosan decreased adhesion of primary melanoma A375 cell line and decreased proliferation of primary melanoma SKMEL28 cell line, it had potent pro-apoptotic effects against RPMI7951, a metastatic melanoma cell line. In these latter cells, inhibition of specific caspases confirmed that apoptosis was effected through the mitochondrial pathway and Western blot analyses showed that chitosan induced an up regulation of pro-apoptotic molecules such as Bax and a down regulation of anti-apoptotic proteins like Bcl-2 and Bcl-XL. More interestingly, chitosan exposure induced an exposition of a greater number of CD95 receptor at RPMI7951 surface, making them more susceptible to FasL-induced apoptosis. Conclusion: Our results indicate that chitosan could be a promising agent for further evaluations in antitumor treatments targeting melanoma. Point 1: This point is very interesting, notably to verify if lower doses could also affect melanoma cells and especially the RPMI7951 metastatic cancer cells. It could also be pertinent to minimize adverse effect on healthy cells. We have evaluated the effect of chitosan concentration on RPMI7951 cell line and normal primary human dermal fibroblasts and it is reported on Fig.5C (for caspase-3 activity) and D (for cell count using WST-1 test).Point 2: Previous the first submission, we had done tests to verify whether apoptosis induction was detectable on fibroblasts but not extensively. Thus, the remark of the reviewer was a chance to improve this paper. Chitosan effect was assessed on adhesion, proliferation and apoptosis of normal primary human dermal fibroblasts. As depicted in fig.5A, apoptotic morphology was not seen when fibroblasts were cultured on chitosan coating as well as no/low caspase activation (Fig.5C, even at high doses of Chitosan, and Fig.5F, even when cultures were continued for 6 days). However, it could be noted that the cell number was reduced ( Fig.5D and E), probably as a result of a reduced proliferation. In vivo, because fibroblasts, unlike cancer cells, have a very slow proliferation rate, chitosan should have a low action on these cells. Cell attachment was tested (Fig.5B) and, even if a delay could be observed in the presence of chitosan after 6 hours, virtually all fibroblasts had adhered on the plate. Point 3: Long term cultures (here 6 days) have been tested. Caspase activation increased substantially when RPMI7951 were seeded onto chitosan coated plates but such a phenomenon could not b...

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Chitosan Induces Apoptosis via Caspase‐3 Activation in Bladder Tumor Cells

Cited by 145 publications

References 32 publications

Polyelectrolyte Biomaterial Interactions Provide Nanoparticulate Carrier for Oral Insulin Delivery

Polyelectrolyte Biomaterial Interactions Provide Nanoparticulate Carrier for Oral Insulin Delivery

Mixed micelles of lipoic acid-chitosan-poly(ethylene glycol) and distearoylphosphatidylethanolamine-poly(ethylene glycol) for tumor delivery

Anticancer properties of chitosan on human melanoma are cell line dependent

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