Heat Shock Proteins HSPA1 and HSP90AA1 Are Upregulated in Colorectal Polyps and Can Be Targeted in Cancer Cells by Anti-Inflammatory Oxicams with Arylpiperazine Pharmacophore and Benzoyl Moiety Substitutions at Thiazine Ring

Heat shock proteins HSPA1/Hsp70α and HSP90AA1/Hsp90α are crucial for cancer growth but their expression pattern in colorectal polyps or whether they can be modulated by oxicams is unknown. We quantified (RTqPCR) <i>HSPA1</i> and <i>HSP90AA1</i> expression in 50 polyp-normal p...

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Autores principales:	Izabela Szczuka, Jarosław Wierzbicki, Paweł Serek, Berenika M. Szczęśniak-Sięga, Małgorzata Krzystek-Korpacka
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	drug repurposing colorectal cancer chemoprevention nonsteroidal anti-inflammatory drugs piroxicam meloxicam Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/281bd43cb52c4e13a6a594018d61ed75
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spelling	oai:doaj.org-article:281bd43cb52c4e13a6a594018d61ed752021-11-25T16:52:29ZHeat Shock Proteins HSPA1 and HSP90AA1 Are Upregulated in Colorectal Polyps and Can Be Targeted in Cancer Cells by Anti-Inflammatory Oxicams with Arylpiperazine Pharmacophore and Benzoyl Moiety Substitutions at Thiazine Ring10.3390/biom111115882218-273Xhttps://doaj.org/article/281bd43cb52c4e13a6a594018d61ed752021-10-01T00:00:00Zhttps://www.mdpi.com/2218-273X/11/11/1588https://doaj.org/toc/2218-273XHeat shock proteins HSPA1/Hsp70α and HSP90AA1/Hsp90α are crucial for cancer growth but their expression pattern in colorectal polyps or whether they can be modulated by oxicams is unknown. We quantified (RTqPCR) <i>HSPA1</i> and <i>HSP90AA1</i> expression in 50 polyp-normal pairs in relation to polyp malignancy potential and examined the effect of piroxicam, meloxicam and five novel analogues on HSPA1 and HSP90AA1 expression (mRNA/protein) in colorectal adenocarcinoma lines. <i>HSPA1</i> and <i>HSP90AA1</i> were upregulated in polyps by 3- and 2.9-fold. Expression ratios were higher in polyps with higher dysplasia grade and dominant villous growth pattern, mostly a result of diminished gene expression in normal tissue. Classic oxicams had negligible/non-significant effect on HSP expression. Their most effective analogue inhibited HSPA1 protein and gene by 2.5-fold and 5.7-fold in Caco-2 and by 11.5-fold and 6.8-fold in HCT116 and HSPA1 protein in HT-29 by 1.9-fold. It downregulated HSP90AA1 protein and gene by 1.9-fold and 3.7-fold in Caco-2 and by 2-fold and 5.0-fold in HCT116. <i>HSPA1</i> and <i>HSP90AA1</i> are upregulated in colorectal polyps reflecting their potential for malignancy. HSPA1 in cancer cells and, to lesser degree, HSP90AA1 can be reduced by oxicam analogues with thiazine ring substituted via propylene linker by arylpiperazine pharmacophore with fluorine substituents and by benzoyl moiety.Izabela SzczukaJarosław WierzbickiPaweł SerekBerenika M. Szczęśniak-SięgaMałgorzata Krzystek-KorpackaMDPI AGarticledrug repurposingcolorectal cancerchemopreventionnonsteroidal anti-inflammatory drugspiroxicammeloxicamMicrobiologyQR1-502ENBiomolecules, Vol 11, Iss 1588, p 1588 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	drug repurposing colorectal cancer chemoprevention nonsteroidal anti-inflammatory drugs piroxicam meloxicam Microbiology QR1-502
spellingShingle	drug repurposing colorectal cancer chemoprevention nonsteroidal anti-inflammatory drugs piroxicam meloxicam Microbiology QR1-502 Izabela Szczuka Jarosław Wierzbicki Paweł Serek Berenika M. Szczęśniak-Sięga Małgorzata Krzystek-Korpacka Heat Shock Proteins HSPA1 and HSP90AA1 Are Upregulated in Colorectal Polyps and Can Be Targeted in Cancer Cells by Anti-Inflammatory Oxicams with Arylpiperazine Pharmacophore and Benzoyl Moiety Substitutions at Thiazine Ring
description	Heat shock proteins HSPA1/Hsp70α and HSP90AA1/Hsp90α are crucial for cancer growth but their expression pattern in colorectal polyps or whether they can be modulated by oxicams is unknown. We quantified (RTqPCR) <i>HSPA1</i> and <i>HSP90AA1</i> expression in 50 polyp-normal pairs in relation to polyp malignancy potential and examined the effect of piroxicam, meloxicam and five novel analogues on HSPA1 and HSP90AA1 expression (mRNA/protein) in colorectal adenocarcinoma lines. <i>HSPA1</i> and <i>HSP90AA1</i> were upregulated in polyps by 3- and 2.9-fold. Expression ratios were higher in polyps with higher dysplasia grade and dominant villous growth pattern, mostly a result of diminished gene expression in normal tissue. Classic oxicams had negligible/non-significant effect on HSP expression. Their most effective analogue inhibited HSPA1 protein and gene by 2.5-fold and 5.7-fold in Caco-2 and by 11.5-fold and 6.8-fold in HCT116 and HSPA1 protein in HT-29 by 1.9-fold. It downregulated HSP90AA1 protein and gene by 1.9-fold and 3.7-fold in Caco-2 and by 2-fold and 5.0-fold in HCT116. <i>HSPA1</i> and <i>HSP90AA1</i> are upregulated in colorectal polyps reflecting their potential for malignancy. HSPA1 in cancer cells and, to lesser degree, HSP90AA1 can be reduced by oxicam analogues with thiazine ring substituted via propylene linker by arylpiperazine pharmacophore with fluorine substituents and by benzoyl moiety.
format	article
author	Izabela Szczuka Jarosław Wierzbicki Paweł Serek Berenika M. Szczęśniak-Sięga Małgorzata Krzystek-Korpacka
author_facet	Izabela Szczuka Jarosław Wierzbicki Paweł Serek Berenika M. Szczęśniak-Sięga Małgorzata Krzystek-Korpacka
author_sort	Izabela Szczuka
title	Heat Shock Proteins HSPA1 and HSP90AA1 Are Upregulated in Colorectal Polyps and Can Be Targeted in Cancer Cells by Anti-Inflammatory Oxicams with Arylpiperazine Pharmacophore and Benzoyl Moiety Substitutions at Thiazine Ring
title_short	Heat Shock Proteins HSPA1 and HSP90AA1 Are Upregulated in Colorectal Polyps and Can Be Targeted in Cancer Cells by Anti-Inflammatory Oxicams with Arylpiperazine Pharmacophore and Benzoyl Moiety Substitutions at Thiazine Ring
title_full	Heat Shock Proteins HSPA1 and HSP90AA1 Are Upregulated in Colorectal Polyps and Can Be Targeted in Cancer Cells by Anti-Inflammatory Oxicams with Arylpiperazine Pharmacophore and Benzoyl Moiety Substitutions at Thiazine Ring
title_fullStr	Heat Shock Proteins HSPA1 and HSP90AA1 Are Upregulated in Colorectal Polyps and Can Be Targeted in Cancer Cells by Anti-Inflammatory Oxicams with Arylpiperazine Pharmacophore and Benzoyl Moiety Substitutions at Thiazine Ring
title_full_unstemmed	Heat Shock Proteins HSPA1 and HSP90AA1 Are Upregulated in Colorectal Polyps and Can Be Targeted in Cancer Cells by Anti-Inflammatory Oxicams with Arylpiperazine Pharmacophore and Benzoyl Moiety Substitutions at Thiazine Ring
title_sort	heat shock proteins hspa1 and hsp90aa1 are upregulated in colorectal polyps and can be targeted in cancer cells by anti-inflammatory oxicams with arylpiperazine pharmacophore and benzoyl moiety substitutions at thiazine ring
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/281bd43cb52c4e13a6a594018d61ed75
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Heat Shock Proteins HSPA1 and HSP90AA1 Are Upregulated in Colorectal Polyps and Can Be Targeted in Cancer Cells by Anti-Inflammatory Oxicams with Arylpiperazine Pharmacophore and Benzoyl Moiety Substitutions at Thiazine Ring

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