Browsing by Author "Al-Trad, Bahaa"

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    Albumin Nano-Encapsulation of Piceatannol Enhances Its Anticancer Potential in Colon Cancer Via Downregulation of Nuclear p65 and HIF-1α
    (2020) Aljabali, Alaa A. A.; Bakshi, Hamid A.; Hakkim, Faruck L.; Haggag, Yusuf A.; Al-Batanyeh, Khalid M.; Al Zoubi, Mazhar S.; Al-Trad, Bahaa; Nasef, Mohamed M.; Satija, Saurabh; Mehta, Meenu; Pabreja, Kavita; Mishra, Vijay; Khan, Mohammed; Abobaker, Salem; Azzouz, Ibrahim M.; Dureja, Harish; Pabari, Ritesh M.; Dardouri, Ashref Ali K.; Kesharwani, Prashant; Gupta, Gaurav; Shukla, Shakti Dhar; Prasher, Parteek; Charbe, Nitin B.; Negi, Poonam; Kapoor, Deepak N.; Chellappan, Dinesh Kumar; da Silva, Mateus Webba; Thompson, Paul; Dua, Kamal; McCarron, Paul; Tambuwala, Murtaza M.
    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-1 alpha. Our results indicate that PIC-BSA NPs were more effective in downregulating the expression of nuclear p65 and HIF-1 alpha 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.
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    Dietary Crocin is Protective in Pancreatic Cancer while Reducing Radiation-Induced Hepatic Oxidative Damage
    (2020) Bakshi, Hamid A.; Al Zoubi, Mazhar S.; Faruck, Hakkim L.; Aljabali, Alaa A. A.; Rabi, Firas A.; Hafiz, Amin A.; Al-Batanyeh, Khalid M.; Al-Trad, Bahaa; Ansari, Prawej; Nasef, Mohamed M.; Charbe, Nitin B.; Satija, Saurabh; Mehta, Meenu; Mishra, Vijay; Gupta, Gaurav; Abobaker, Salem; Negi, Poonam; Azzouz, Ibrahim M.; Dardouri, Ashref Ali K.; Dureja, Harish; Prasher, Parteek; Chellappan, Dinesh K.; Dua, Kamal; Da Silva, Mateus Webba; El Tanani, Mohamed; McCarron, Paul A.; Tambuwala, Murtaza M.
    Pancreatic cancer is one of the fatal causes of global cancer-related deaths. Although surgery and chemotherapy are standard treatment options, post-treatment outcomes often end in a poor prognosis. In the present study, we investigated anti-pancreatic cancer and amelioration of radiation-induced oxidative damage by crocin. Crocin is a carotenoid isolated from the dietary herb saffron, a prospect for novel leads as an anti-cancer agent. Crocin significantly reduced cell viability of BXPC3 and Capan-2 by triggering caspase signaling via the downregulation of Bcl-2. It modulated the expression of cell cycle signaling proteins P53, P21, P27, CDK2, c-MYC, Cyt-c and P38. Concomitantly, crocin treatment-induced apoptosis by inducing the release of cytochrome c from mitochondria to cytosol. Microarray analysis of the expression signature of genes induced by crocin showed a substantial number of genes involved in cell signaling pathways and checkpoints (723) are significantly affected by crocin. In mice bearing pancreatic tumors, crocin significantly reduced tumor burden without a change in body weight. Additionally, it showed significant protection against radiation-induced hepatic oxidative damage, reduced the levels of hepatic toxicity and preserved liver morphology. These findings indicate that crocin has a potential role in the treatment, prevention and management of pancreatic cancer.
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    Dynamics of Prolyl Hydroxylases Levels During Disease Progression in Experimental Colitis
    (2019) Bakshi, Hamid A.; Mishra, Vijay; Satija, Saurabh; Mehta, Meenu; Hakkim, Faruk L.; Kesharwani, Prashant; Dua, Kamal; Chellappan, Dinesh K.; Charbe, Nitin B.; Shrivastava, Garima; Rajeshkumar, S.; Aljabali, Alaa A.; Al-Trad, Bahaa; Pabreja, Kavita; Tambuwala, Murtaza M.
    Hypoxia inducible factor (HIF)-prolyl hydroxylase (PHD) inhibitors are shown to be protective in several models of inflammatory bowel disease (IBD). However, these non-selective inhibitors are known to inhibit all the three isoforms of PHD, i.e. PHD-1, PHD-2 and PHD-3. In the present report, we investigated the associated changes in levels of PHDs during the development and recovery of chemically induced colitis in mice. The results indicated that in the experimental model of murine colitis, levels of both, PHD-1 and PHD-2 were found to be increased with the progression of the disease; however, the level of PHD-3 remained the same in group of healthy controls and mice with colitis. Thus, the findings advocated that inhibitors, which inhibited all three isoforms of PHD could not be ideal therapeutics for IBD since PHD-3 is required for normal gut function. Hence, this necessitates the development of new compounds capable of selectively inhibiting PHD-1 and PHD-2 for effective treatment of IBD.