Resveratrol Loaded Liposomes Disrupt Cancer Associated Fibroblast Communications within the Tumor Microenvironment to Inhibit Colorectal Cancer Aggressiveness

Colorectal cancer (CRC) is a cancer-associated fibroblast, CAF-rich tumor. CAF promotes cancer cell proliferation, metastasis, drug resistance via secretes soluble factors, and extracellular matrices which leads to dense stroma, a major barrier for drug delivery. Resveratrol (RES) is a polyphenolic...

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Main Authors: Paweena Dana, Nutthanit Thumrongsiri, Prattana Tanyapanyachon, Walailuk Chonniyom, Primana Punnakitikashem, Nattika Saengkrit
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Nanomaterials
Subjects:
Online Access:https://www.mdpi.com/2079-4991/13/1/107
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author Paweena Dana
Nutthanit Thumrongsiri
Prattana Tanyapanyachon
Walailuk Chonniyom
Primana Punnakitikashem
Nattika Saengkrit
author_facet Paweena Dana
Nutthanit Thumrongsiri
Prattana Tanyapanyachon
Walailuk Chonniyom
Primana Punnakitikashem
Nattika Saengkrit
author_sort Paweena Dana
collection DOAJ
description Colorectal cancer (CRC) is a cancer-associated fibroblast, CAF-rich tumor. CAF promotes cancer cell proliferation, metastasis, drug resistance via secretes soluble factors, and extracellular matrices which leads to dense stroma, a major barrier for drug delivery. Resveratrol (RES) is a polyphenolic compound, has several pharmacologic functions including anti-inflammation and anticancer effects. Considering tumor microenvironment of CRC, resveratrol-loaded liposome (L-RES) was synthesized and employed to inhibit CAF functions. The L-RES was synthesized by thin-film hydration method. The cytotoxicity of L-RES was evaluated using MTT assay. Effect of L-RES treated CAF on tumor spheroid growth was performed. Cell invasion was determined using spheroid invasion assay. The effect of L-RES on 5-fluorouracil (5-FU) sensitivity of CRC cells was determined in co-cultured tumor spheroids. Subtoxic dose of L-RES was selected to study possible inhibiting CAF functions. Decreased CAF markers, α-SMA and IL-6 levels, were observed in L-RES treated activated fibroblast. Interestingly, the activated fibroblast promoted invasive ability and drug resistance of CRC cells in co-culture condition of both 2D and 3D cultures and was attenuated by L-RES treatment in the activated fibroblast. Therefore, L-RES provides a promising drug delivery strategy for CRC treatment by disrupting the crosstalk between CRC cells and CAF.
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spelling doaj.art-4f9edf4379fe4c2f920bda67876365a92023-12-02T00:44:27ZengMDPI AGNanomaterials2079-49912022-12-0113110710.3390/nano13010107Resveratrol Loaded Liposomes Disrupt Cancer Associated Fibroblast Communications within the Tumor Microenvironment to Inhibit Colorectal Cancer AggressivenessPaweena Dana0Nutthanit Thumrongsiri1Prattana Tanyapanyachon2Walailuk Chonniyom3Primana Punnakitikashem4Nattika Saengkrit5National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani 12120, ThailandNational Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani 12120, ThailandNational Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani 12120, ThailandNational Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani 12120, ThailandDepartment of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok 10700, ThailandNational Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani 12120, ThailandColorectal cancer (CRC) is a cancer-associated fibroblast, CAF-rich tumor. CAF promotes cancer cell proliferation, metastasis, drug resistance via secretes soluble factors, and extracellular matrices which leads to dense stroma, a major barrier for drug delivery. Resveratrol (RES) is a polyphenolic compound, has several pharmacologic functions including anti-inflammation and anticancer effects. Considering tumor microenvironment of CRC, resveratrol-loaded liposome (L-RES) was synthesized and employed to inhibit CAF functions. The L-RES was synthesized by thin-film hydration method. The cytotoxicity of L-RES was evaluated using MTT assay. Effect of L-RES treated CAF on tumor spheroid growth was performed. Cell invasion was determined using spheroid invasion assay. The effect of L-RES on 5-fluorouracil (5-FU) sensitivity of CRC cells was determined in co-cultured tumor spheroids. Subtoxic dose of L-RES was selected to study possible inhibiting CAF functions. Decreased CAF markers, α-SMA and IL-6 levels, were observed in L-RES treated activated fibroblast. Interestingly, the activated fibroblast promoted invasive ability and drug resistance of CRC cells in co-culture condition of both 2D and 3D cultures and was attenuated by L-RES treatment in the activated fibroblast. Therefore, L-RES provides a promising drug delivery strategy for CRC treatment by disrupting the crosstalk between CRC cells and CAF.https://www.mdpi.com/2079-4991/13/1/107resveratrolcolorectal cancercancer associated fibroblastmetastasisdrug sensitivityliposome
spellingShingle Paweena Dana
Nutthanit Thumrongsiri
Prattana Tanyapanyachon
Walailuk Chonniyom
Primana Punnakitikashem
Nattika Saengkrit
Resveratrol Loaded Liposomes Disrupt Cancer Associated Fibroblast Communications within the Tumor Microenvironment to Inhibit Colorectal Cancer Aggressiveness
Nanomaterials
resveratrol
colorectal cancer
cancer associated fibroblast
metastasis
drug sensitivity
liposome
title Resveratrol Loaded Liposomes Disrupt Cancer Associated Fibroblast Communications within the Tumor Microenvironment to Inhibit Colorectal Cancer Aggressiveness
title_full Resveratrol Loaded Liposomes Disrupt Cancer Associated Fibroblast Communications within the Tumor Microenvironment to Inhibit Colorectal Cancer Aggressiveness
title_fullStr Resveratrol Loaded Liposomes Disrupt Cancer Associated Fibroblast Communications within the Tumor Microenvironment to Inhibit Colorectal Cancer Aggressiveness
title_full_unstemmed Resveratrol Loaded Liposomes Disrupt Cancer Associated Fibroblast Communications within the Tumor Microenvironment to Inhibit Colorectal Cancer Aggressiveness
title_short Resveratrol Loaded Liposomes Disrupt Cancer Associated Fibroblast Communications within the Tumor Microenvironment to Inhibit Colorectal Cancer Aggressiveness
title_sort resveratrol loaded liposomes disrupt cancer associated fibroblast communications within the tumor microenvironment to inhibit colorectal cancer aggressiveness
topic resveratrol
colorectal cancer
cancer associated fibroblast
metastasis
drug sensitivity
liposome
url https://www.mdpi.com/2079-4991/13/1/107
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AT prattanatanyapanyachon resveratrolloadedliposomesdisruptcancerassociatedfibroblastcommunicationswithinthetumormicroenvironmenttoinhibitcolorectalcanceraggressiveness
AT walailukchonniyom resveratrolloadedliposomesdisruptcancerassociatedfibroblastcommunicationswithinthetumormicroenvironmenttoinhibitcolorectalcanceraggressiveness
AT primanapunnakitikashem resveratrolloadedliposomesdisruptcancerassociatedfibroblastcommunicationswithinthetumormicroenvironmenttoinhibitcolorectalcanceraggressiveness
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