Laure Gibot1, Stéphane Chabaud1, Sara Bouhout1, Stéphane Bolduc2, François A Auger2, Véronique J Moulin3. 1. Centre de Recherche en Organogenese Experimentale de l'Universite Laval/LOEX, Division of Regenerative Medicine, CHU de Quebec research center/FRQS, Faculty of Medicine, Universite Laval, Quebec city, Canada. 2. Centre de Recherche en Organogenese Experimentale de l'Universite Laval/LOEX, Division of Regenerative Medicine, CHU de Quebec research center/FRQS, Faculty of Medicine, Universite Laval, Quebec city, Canada; Department of Surgery, Faculty of Medicine, Université Laval, Quebec, QC, Canada. 3. Centre de Recherche en Organogenese Experimentale de l'Universite Laval/LOEX, Division of Regenerative Medicine, CHU de Quebec research center/FRQS, Faculty of Medicine, Universite Laval, Quebec city, Canada; Department of Surgery, Faculty of Medicine, Université Laval, Quebec, QC, Canada. Electronic address: veronique.moulin@chg.ulaval.ca.
Abstract
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.
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.
Authors: Sofia Piña Olmos; Roberto Díaz Torres; Eman Elbakrawy; Louise Hughes; Joseph Mckenna; Mark A Hill; Munira Kadhim; Patricia Ramírez Noguera; Victor M Bolanos-Garcia Journal: Biomolecules Date: 2019-05-12
Authors: Annise Proboningrat; Amaq Fadholly; Regina Purnama Dewi Iskandar; Agung Budianto Achmad; Fedik Abdul Rantam; Sri Agus Sudjarwo Journal: Vet World Date: 2019-10-25