Albumin Nano-Encapsulation of Piceatannol Enhances Its Anticancer Potential in Colon Cancer Via Downregulation of Nuclear p65 and HIF-1α

Alaa A A Aljabali; Hamid A Bakshi; Faruk L Hakkim; Yusuf A Haggag; Khalid M Al-Batanyeh; Mazhar S Al Zoubi; Bahaa Al-Trad; Mohamed M Nasef; Saurabh Satija; Meenu Mehta; Kavita Pabreja; Vijay Mishra; Mohammed Khan; Salem Abobaker; Ibrahim M Azzouz; Harish Dureja; Ritesh M Pabari; Ashref Ali K Dardouri; Prashant Kesharwani; Gaurav Gupta; Shakti Dhar Shukla; Parteek Prasher; Nitin B Charbe; Poonam Negi; Deepak N Kapoor; Dinesh Kumar Chellappan; Mateus Webba da Silva; Paul Thompson; Kamal Dua; Paul McCarron; Murtaza M Tambuwala

doi:10.3390/cancers12010113

Albumin Nano-Encapsulation of Piceatannol Enhances Its Anticancer Potential in Colon Cancer Via Downregulation of Nuclear p65 and HIF-1α

Cancers (Basel). 2020 Jan 1;12(1):113. doi: 10.3390/cancers12010113.

Authors

Alaa A A Aljabali¹, Hamid A Bakshi², Faruk L Hakkim³, Yusuf A Haggag⁴, Khalid M Al-Batanyeh⁵, Mazhar S Al Zoubi⁶, Bahaa Al-Trad⁶, Mohamed M Nasef⁷, Saurabh Satija⁸, Meenu Mehta⁸, Kavita Pabreja⁸, Vijay Mishra⁸, Mohammed Khan², Salem Abobaker⁹, Ibrahim M Azzouz¹⁰, Harish Dureja¹¹, Ritesh M Pabari¹², Ashref Ali K Dardouri¹³, Prashant Kesharwani¹⁴, Gaurav Gupta¹⁵, Shakti Dhar Shukla¹⁶, Parteek Prasher¹⁷, Nitin B Charbe¹⁸, Poonam Negi¹⁹, Deepak N Kapoor¹⁹, Dinesh Kumar Chellappan²⁰, Mateus Webba da Silva², Paul Thompson²¹, Kamal Dua^{16

19

22

23}, Paul McCarron², Murtaza M Tambuwala²

Affiliations

¹ Department of Pharmaceutical Sciences, Yarmouk University-Faculty of Pharmacy, Irbid 566, Jordan.
² School of Pharmacy and Pharmaceutical Science, Ulster University, Coleraine, County Londonderry, Northern Ireland BT52 1SA, UK.
³ Department of Mathematics and Sciences, College of Arts and Applied Sciences Dhofar University Salalah, Salalah 211, Oman.
⁴ Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Tanta, Tanta 31111, Egypt.
⁵ Department of Biological Sciences,Yarmouk University-Faculty of Science, Irbid 566, Jordan.
⁶ Department of Basic Medical Sciences, Yarmouk University-Faculty of Medicine, Irbid 566, Jordan.
⁷ Department of Pharmacy and Biomedical Sciences, School of Applied Sciences, University of Huddersfield, Queensgate, Huddersfield HD13DH, UK.
⁸ School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India.
⁹ Department of Gynecology, European Competence Center for Ovarian Cancer, Campus Virchow, Klinikum Charite-Universitatmedizin Berlin, augustenburger Platz 1, Berlin 13353, Germany.
¹⁰ Department of Dermatology, Venerology, and allergology, Charite-Universitatsmedizin Berlin, corporate member of Freie Universitat Berlin, Chariteplatz1, Berlin 10117, Germany.
¹¹ Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak 124001, India.
¹² School of Pharmacy, Royal College of Surgeons in Ireland, Dublin-09 D02 YN77, Ireland.
¹³ Department of Forensic Science, School of Applied Science, Huddersfield University, Queensgate, Huddersfield HD1 3DH, UK.
¹⁴ Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India.
¹⁵ School of Pharmacy, Suresh Gyan Vihar University, Jagatpura, Jaipur 302017, India.
¹⁶ Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute (HMRI) and School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales NSW 230, Australia.
¹⁷ Department of Chemistry, University of Petroleum & Energy Studies, Dehradun 248007, India.
¹⁸ Departamento de Química Orgánica, Facultad de Química y de Farmacia, Pontificia Universidad Católica de Chile, Av. Vicuña McKenna 4860, 7820436, Macul, Santiago 4860, Chile.
¹⁹ School of Pharmaceutical Sciences, Shoolini University of Biotechnology and Management Sciences, Solan, India 173229, India.
²⁰ Department of Life Sciences, School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur 57000, Malaysia.
²¹ School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland, BT52 1SA, UK.
²² Discipline of Pharmacy, Graduate School of Health, University of Technology, Sydney, NSW 2007, Australia.
²³ Centre for Inflammation, Centenary Institute, Sydney, NSW 2050, Australia 2308, Australia.

Abstract

Piceatannol (PIC) is known to have anticancer activity, which has been attributed to its ability to block the proliferation of cancer cells via suppression of the NF-kB signaling pathway. However, its effect on hypoxia-inducible factor (HIF) is not well known in cancer. In this study, PIC was loaded into bovine serum albumin (BSA) by desolvation method as PIC-BSA nanoparticles (NPs). These PIC-BSA nanoparticles were assessed for in vitro cytotoxicity, migration, invasion, and colony formation studies and levels of p65 and HIF-1α. Our results indicate that PIC-BSA NPs were more effective in downregulating the expression of nuclear p65 and HIF-1α in colon cancer cells as compared to free PIC. We also observed a significant reduction in inflammation induced by chemical colitis in mice by PIC-BSA NPs. Furthermore, a significant reduction in tumor size and number of colon tumors was also observed in the murine model of colitis-associated colorectal cancer, when treated with PIC-BSA NPs as compared to free PIC. The overall results indicate that PIC, when formulated as PIC-BSA NPs, enhances its therpautice potential. Our work could prompt further research in using natural anticancer agents as nanoparticels with possiable human clinical trails. This could lead to the development of a new line of safe and effective therapeutics for cancer patients.

Keywords: HIF-1α; albumin nanoparticles; colon cancer; nuclear P65; piceatannol.

Grants and funding

RCF-2014/Ulster University/International