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

Alaa A A Aljabali,Dinesh Kumar Chellappan,Ritesh M Pabari,Ashref Ali K Dardouri,Harish Dureja,Murtaza M Tambuwala,Poonam Negi,Gaurav Gupta,Meenu Mehta,Parteek Prasher,Yusuf A Haggag,Kamal Dua,Saurabh Satija,Khalid M Al-Batanyeh,Kavita Pabreja,Ibrahim M Azzouz,Salem Abobaker,Vijay Mishra,Hamid A Bakshi,Mateus Webba Da Silva,Prashant Kesharwani,Paul Thompson,Deepak Kapoor ,Nitin Charbe ,Mohammed Naeem Khan ,Faruck Lukmanul Hakkim ,Bahaa Al‐Trad ,Mohamed Mahmoud Nasef ,Shakti D Shukla ,Mazhar Salim Al Zoubi ,Paul A Mccarron

doi:10.3390/cancers12010113

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 therapeutic potential. Our work could prompt further research in using natural anticancer agents as nanoparticels with possible human clinical trails. This could lead to the development of a new line of safe and effective therapeutics for cancer patients.

Highlights

Colorectal cancer (CRC) is the third most common cancer in men and the second in women worldwide, with a prevalence of 10.0 and 9.2%, respectively [1,2,3]
The results indicate that PIC-loaded albumin NPs are 2 cells treated with PIC–bovine serum albumin (BSA) NPs as compared to free PIC (51%) (Figure 4B)
The results indicate that PIC–BSA NPs are effective against the downregulation of hypoxia-inducible factor (HIF)-1α that leads to the reduction in proliferation, migration, and invasion of the tumor

Summary

Introduction

Colorectal cancer (CRC) is the third most common cancer in men and the second in women worldwide, with a prevalence of 10.0 and 9.2%, respectively [1,2,3]. The potential of nutraceutical natural compounds such as flavonoids, polyphenols, anthocyanins, carotenoids, or terpenoids for cancer prevention has been widely investigated, and there are many pieces of evidence supporting that moderate consumption of fruits and vegetables is correlated with decreased risk of CRC [7] Some members of these families of compounds can modulate signaling pathways, as well as regulate the expression of genes involved in cell cycle regulation, differentiation, and apoptosis [8]. It is well documented that pro-inflammatory cytokines induce aberrant activation of NF-κβ and HIF-1α in ulcerative colitis and colorectal cancer patients [16,17,18]. This would make NF-κβ and HIF-1α proteins potential targets for effective treatment of colorectal cancer

Methods

Results

Conclusion