Anticancer Activity of Novel Difluorinated Curcumin Analog and Its Inclusion Complex with 2-Hydroxypropyl-β-Cyclodextrin against Pancreatic Cancer
Pancreatic ductal adenocarcinoma (PDAC) is the primary reason for cancer-related deaths in the US. Genetic mutations, drug resistance, the involvement of multiple signaling pathways, cancer stem cells (CSCs), and desmoplastic stroma, which hinders drug penetrance, contribute to poor chemotherapeutic...
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| Format: | Article |
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/7/6336 |
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| author | Sangita Bhattacharyya Hindole Ghosh Obdulia Covarrubias-Zambrano Krishan Jain K. Venkateswara Swamy Anup Kasi Ameer Hamza Shrikant Anant Michael VanSaun Scott J. Weir Stefan H. Bossmann Subhash B. Padhye Prasad Dandawate |
| author_facet | Sangita Bhattacharyya Hindole Ghosh Obdulia Covarrubias-Zambrano Krishan Jain K. Venkateswara Swamy Anup Kasi Ameer Hamza Shrikant Anant Michael VanSaun Scott J. Weir Stefan H. Bossmann Subhash B. Padhye Prasad Dandawate |
| author_sort | Sangita Bhattacharyya |
| collection | DOAJ |
| description | Pancreatic ductal adenocarcinoma (PDAC) is the primary reason for cancer-related deaths in the US. Genetic mutations, drug resistance, the involvement of multiple signaling pathways, cancer stem cells (CSCs), and desmoplastic stroma, which hinders drug penetrance, contribute to poor chemotherapeutic efficacy. Hence, there is a need to identify novel drugs with improved delivery to improve treatment outcomes. Curcumin is one such compound that can inhibit multiple signaling pathways and CSCs. However, curcumin’s clinical applicability for treating PDAC is limited because of its poor solubility in water and metabolic instability. Hence, we developed a difluorinated curcumin (CDF) analog that accumulates selectively in the pancreas and inhibits PDAC growth in vitro and in vivo. In the present work, we developed its 2-hydroxy-propyl-β-cyclodextrin (HCD) inclusion complex to increase its water solubility and hydrolytic stability. The CDFHCD inclusion complex was characterized by spectroscopic, thermal, and microscopic techniques. The inclusion complex exhibited increased aqueous solubility, hydrolytic stability, and antiproliferative activity compared to parent CDF. Moreover, CDF and CDFHCD inhibited colony and spheroid formation, and induced cell cycle and apoptosis in PDAC cell lines. Hence, CDFHCD self-assembly is an efficient approach to increase water solubility and anticancer therapeutic efficacy, which now warrants advancement towards a clinical proof of concept in PDAC patients. |
| first_indexed | 2024-03-11T05:36:09Z |
| format | Article |
| id | doaj.art-bcd519e0deb046baaf12a90c86b0da00 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T05:36:09Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-bcd519e0deb046baaf12a90c86b0da002023-11-17T16:49:39ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01247633610.3390/ijms24076336Anticancer Activity of Novel Difluorinated Curcumin Analog and Its Inclusion Complex with 2-Hydroxypropyl-β-Cyclodextrin against Pancreatic CancerSangita Bhattacharyya0Hindole Ghosh1Obdulia Covarrubias-Zambrano2Krishan Jain3K. Venkateswara Swamy4Anup Kasi5Ameer Hamza6Shrikant Anant7Michael VanSaun8Scott J. Weir9Stefan H. Bossmann10Subhash B. Padhye11Prasad Dandawate12Department of Cancer Biology, University of Kansas Medical Center, Kansas City, KS 66103, USADepartment of Cancer Biology, University of Kansas Medical Center, Kansas City, KS 66103, USADepartment of Cancer Biology, University of Kansas Medical Center, Kansas City, KS 66103, USADepartment of Cancer Biology, University of Kansas Medical Center, Kansas City, KS 66103, USAMIT School of Bioengineering, Sciences & Research, MIT Art, Design and Technology University, Pune 412201, IndiaDivision of Medical Oncology, University of Kansas, Kansas City, KS 66160, USAPathology and Laboratory Medicine, University of Kansas, Kansas City, KS 66160, USADepartment of Cancer Biology, University of Kansas Medical Center, Kansas City, KS 66103, USADepartment of Cancer Biology, University of Kansas Medical Center, Kansas City, KS 66103, USADepartment of Cancer Biology, University of Kansas Medical Center, Kansas City, KS 66103, USADepartment of Cancer Biology, University of Kansas Medical Center, Kansas City, KS 66103, USADepartment of Cancer Biology, University of Kansas Medical Center, Kansas City, KS 66103, USADepartment of Cancer Biology, University of Kansas Medical Center, Kansas City, KS 66103, USAPancreatic ductal adenocarcinoma (PDAC) is the primary reason for cancer-related deaths in the US. Genetic mutations, drug resistance, the involvement of multiple signaling pathways, cancer stem cells (CSCs), and desmoplastic stroma, which hinders drug penetrance, contribute to poor chemotherapeutic efficacy. Hence, there is a need to identify novel drugs with improved delivery to improve treatment outcomes. Curcumin is one such compound that can inhibit multiple signaling pathways and CSCs. However, curcumin’s clinical applicability for treating PDAC is limited because of its poor solubility in water and metabolic instability. Hence, we developed a difluorinated curcumin (CDF) analog that accumulates selectively in the pancreas and inhibits PDAC growth in vitro and in vivo. In the present work, we developed its 2-hydroxy-propyl-β-cyclodextrin (HCD) inclusion complex to increase its water solubility and hydrolytic stability. The CDFHCD inclusion complex was characterized by spectroscopic, thermal, and microscopic techniques. The inclusion complex exhibited increased aqueous solubility, hydrolytic stability, and antiproliferative activity compared to parent CDF. Moreover, CDF and CDFHCD inhibited colony and spheroid formation, and induced cell cycle and apoptosis in PDAC cell lines. Hence, CDFHCD self-assembly is an efficient approach to increase water solubility and anticancer therapeutic efficacy, which now warrants advancement towards a clinical proof of concept in PDAC patients.https://www.mdpi.com/1422-0067/24/7/6336curcumindifluorinated curcuminCDFpancreatic cancerPDAC2-hydroxypropyl-β-cyclodextrin |
| spellingShingle | Sangita Bhattacharyya Hindole Ghosh Obdulia Covarrubias-Zambrano Krishan Jain K. Venkateswara Swamy Anup Kasi Ameer Hamza Shrikant Anant Michael VanSaun Scott J. Weir Stefan H. Bossmann Subhash B. Padhye Prasad Dandawate Anticancer Activity of Novel Difluorinated Curcumin Analog and Its Inclusion Complex with 2-Hydroxypropyl-β-Cyclodextrin against Pancreatic Cancer International Journal of Molecular Sciences curcumin difluorinated curcumin CDF pancreatic cancer PDAC 2-hydroxypropyl-β-cyclodextrin |
| title | Anticancer Activity of Novel Difluorinated Curcumin Analog and Its Inclusion Complex with 2-Hydroxypropyl-β-Cyclodextrin against Pancreatic Cancer |
| title_full | Anticancer Activity of Novel Difluorinated Curcumin Analog and Its Inclusion Complex with 2-Hydroxypropyl-β-Cyclodextrin against Pancreatic Cancer |
| title_fullStr | Anticancer Activity of Novel Difluorinated Curcumin Analog and Its Inclusion Complex with 2-Hydroxypropyl-β-Cyclodextrin against Pancreatic Cancer |
| title_full_unstemmed | Anticancer Activity of Novel Difluorinated Curcumin Analog and Its Inclusion Complex with 2-Hydroxypropyl-β-Cyclodextrin against Pancreatic Cancer |
| title_short | Anticancer Activity of Novel Difluorinated Curcumin Analog and Its Inclusion Complex with 2-Hydroxypropyl-β-Cyclodextrin against Pancreatic Cancer |
| title_sort | anticancer activity of novel difluorinated curcumin analog and its inclusion complex with 2 hydroxypropyl β cyclodextrin against pancreatic cancer |
| topic | curcumin difluorinated curcumin CDF pancreatic cancer PDAC 2-hydroxypropyl-β-cyclodextrin |
| url | https://www.mdpi.com/1422-0067/24/7/6336 |
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