Combination of Ashwagandha water extract and
intermittent fasting as a therapy to overcome cisplatin resistance in breast cancer
Authors : Sajidah Jawarneh and Wamidh H. Talib*
Abstract : Breast cancer is considered a universal public health dilemma in women. Due to the high toxicity and low selectivity of conventional anticancer therapies, there is a growing trend of using plant-derived natural products in cancer prevention and therapy. Ashwagandha (Withania somnifera, WS) has been used in the Mediterranean region and Ayurvedic medicine for millennia as a functional food and a medicinal plant with anticancer activity. Besides, intermittent fasting (IF) has been engaged recently in cancer treatment. Hence, the combination of WS and IF provides possible solutions to treat cancer and reduce chemoresistance when combined with chemotherapy. In this study, WS root (WSR), IF, and cisplatin were tested on cisplatin-sensitive (EMT6/P) and cisplatin-resistant (EMT6/CPR) mouse mammary cell lines. The phytochemical content of the WSR extract was analyzed using liquid chromatography–mass spectrometry (LC-MS) analysis. Antiproliferative and apoptotic effects were assessed for WSR extract, cisplatin, and their combination in vitro using [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] (MTT) and caspase-3 assays. An in vivo study was used to assess the effect of WSR extract, IF, cisplatin, and their combinations in mice inculcated with EMT6/P and EMT6/CPR cells. The safety profile was also investigated using liver enzymes and creatinine assays. In vitro, WSR extract and cisplatin had a synergistic effect in both cell lines. The same combination induced an apoptotic effect higher than the single treatment in both cell lines. In vivo, several combinations of WSR extract, IF, or cisplatin caused significant tumor size reduction and improved the cure rate in mice implanted with EMT6/P and EMT6/CPR cell lines. IF-treated groups showed a significant reduction in serum glucose and an elevation in β-hydroxybutyrate (BHB) levels. In the safety profile, WSR extract, IF, and their combinations were safe. Overall, the combination of WSR extract and IF provides a promising solution for breast cancer treatment besides cisplatin by reducing the proliferation of cancer cells through induction of apoptosis. Moreover, they minimize cisplatin toxicity to the liver and kidney.
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Folic acid-hydrophilic polymer coated mesoporous silica nanoparticles target doxorubicin
delivery
Authors : Al- Nadaf, A. H., Dahabiyeh, L. A., Jawarneh, S., Bardaweel, S., & Mahmoud, N. N.
Abstract : Mesoporous silica nanoparticles (MSNs) gained significant attention, particularly in the pharmaceutical field. Folic acid (FA) shows marked promise as a targeting agent for its specific interaction with the folate receptor. This receptor is over-expressed on the cell surface of several cancerous cells like breast cancer. Polyethylene glycol (PE), as well as polypropylene glycol (PEG), is used to decorate nanoparticles to improve their biodistribution. Moreover, carboxymethyl beta-cyclodextrin (CM-β-CD), is used as a complexation molecule. In this study, we described the chemical synthesis, in vitro drug release and antiproliferative activity of doxorubicin-loaded/decorated MSNs further coupled with FA in two conditions: chemically bound or as a complex with CM-β-CD. Fourier Transform Infrared Spectroscopy with Transmission Electron Microscopy confirmed the successful surface change. Dynamic Light Scattering confirmed the change in surface characters like zeta potential, polydispersity index (PI), and size. PI improved from 0.58 to 0.23 while the size enlarged from 200 to 348 and 532 nm. Functionalized nanoparticles demonstrated more significant drug entrapment with (97%) while undecorated MSNs only showed (63%). Accordingly, we effectively synthesized FA-PEG2000-MSNs with IC50: 0.015 mg/mL targeting HeLa cells. This approach may allow potential applications as a drug delivery system in cancer chemotherapy.
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The impact of herbal infusion consumption on oxidative stress and cancer: the good,
the bad, the misunderstood. Molecules
Authors : Talib, W. H., Al-Ataby, I. A., Mahmod, A. I., Jawarneh, S., Al Kury, L. T., & Al-Yasari, I. H
Abstract : The release of reactive oxygen species (ROS) and oxidative stress is associated with the development of many ailments, including cardiovascular diseases, diabetes and cancer. The causal link between oxidative stress and cancer is well established and antioxidants are suggested as a protective mechanism against cancer development. Recently, an increase in the consumption of antioxidant supplements was observed globally. The main sources of these antioxidants include fruits, vegetables, and beverage. Herbal infusions are highly popular beverages consumed daily for different reasons. Studies showed the potent antioxidant effects of plants used in the preparation of some herbal infusions. Such herbal infusions represent an important source of antioxidants and can be used as a dietary protection against cancer. However, uncontrolled consumption of herbal infusions may cause toxicity and reduced antioxidant activity. In this review, eleven widely consumed herbal infusions were evaluated for their antioxidant capacities, anticancer potential and possible toxicity. These herbal infusions are highly popular and consumed as daily drinks in different countries. Studies discussed in this review will provide a solid ground for researchers to have better understanding of the use of herbal infusions to reduce oxidative stress and as protective supplements against cancer development.
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Functionalized mesoporous silica nanoparticles by lactose and hydrophilic polymer as a
hepatocellular carcinoma drug delivery system. Journal of Drug Delivery Science and
Technology
Authors : Al-Nadaf, A. H., Dahabiyeh, L. A., Bardaweel, S., Mahmoud, N. N., & Jawarneh, S.
Abstract : Surface modification has a strong impact on mesoporous silica nanoparticles (MSNs) performance as drug carriers. Here, we described the chemical synthesis; in vitro drug release and cytotoxicity of MSNs decorated with poly ethylene glycol (PEG) or poly propylene glycol PPG as an outer shell wrap for nanoparticles (NPs). The lactose, glucosylgalactose, was used to provide a specific interaction with the asialoglycoprotein receptor which is expressed on the cell surface of hepatoma. Fourier transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM) confirmed successful chemical surface modification while Dynamic Light Scattering (DLS) confirmed the surface characteristic changes as size; polydispersity index (PI) and zeta potential. Our results showed that the PI was improved from 0.58 to 0.28 while size has been enlarged from 200 to 357 and 580 nm. A higher percentage of drug entrapment (doxorubicin) was observed with functionalized NPs (94%) compared to plain MSNs (63%). In this study, we effectively synthesized lactose-PPG-MSNs targeting HepG2 cells with IC50 of 0.07 mg/mL when loaded with doxorubicin. This study may provide a useful approach for designing and improving the applicability of MSNs as a promising drug delivery system in hepatocellular carcinoma.
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