Thymoquinone enhances the antioxidant and anticancer activity of Lebanese propolis

BACKGROUND Reactive oxygen species(ROS)are produced by multiple cellular processes and are maintained at optimal levels in normal cells by endogenous antioxidants.In recent years,the search for potential exogenous antioxidants from dietary sources has gained considerable attention to eliminate excess ROS that is associated with oxidative stress related diseases including cancer.Propolis,a resinous honeybee product,has been shown to have protective effects against oxidative stress and anticancer effects against several types of neoplasms.AIM To investigate the antioxidant and anticancer potential of Lebanese propolis when applied alone or in combination with the promising anticancer compound Thymoquinone(TQ)the main constituent of Nigella sativa essential oil.METHODS Crude extracts of Lebanese propolis collected from two locations,Rashaya and Akkar-Danniyeh,were prepared in methanol and the total phenolic content was determined by Folin–Ciocalteu method.The antioxidant activity was assessed by the ability to scavenge 2,2-diphenyl-1-picrylhydrazyl(DPPH)free radical and to inhibit H2O2-induced oxidative hemolysis of human erythrocytes.The anticancer activity was evaluated by[3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide]MTT assay against HCT-116 human colorectal cancer cells and MDAMB-231 human breast cancer cells.RESULTS The total phenolic content of propolis extract from Rashaya and Akkar-Danniyeh were 56.81μg and 83.503μg of gallic acid equivalent/mg of propolis,respectively.Both natural agents exhibited strong antioxidant activities as evidenced by their ability to scavenge DPPH free radical and to protect erythrocytes against H2O2-induced hemolysis.They also dose-dependently decreased the viability of both cancer cell lines.The IC50 value of each of propolis extract from Rashaya and Akkar-Danniyeh or TQ was 22.3,61.7,40.44μg/mL for breast cancer cells at 72 h and 33.3,50.9,33.5μg/mL for colorectal cancer cells at the same time point,respectively.Importantly,the inhibitory effects of propolis on DPPH radicals and cancer cell viability were achieved at half its concentration when combined with TQ.CONCLUSION Our results indicate that Lebanese propolis extract has antioxidant and anticancer potential and its combination with TQ could possibly prevent ROS-mediated diseases.

Therapeutic potential of thymoquinone in combination therapy against cancer and cancer stem cells

The long-term success of standard anticancer monotherapeutic strategies has been hampered by intolerable side effects,resistance to treatment and cancer relapse.These monotherapeutic strategies shrink the tumor bulk but do not effectively eliminate the population of self-renewing cancer stem cells(CSCs)that are normally present within the tumor.These surviving CSCs develop mechanisms of resistance to treatment and refuel the tumor,thus causing cancer relapse.To ensure durable tumor control,research has moved away from adopting the monotreatment paradigm towards developing and using combination therapy.Combining different therapeutic modalities has demonstrated significant therapeutic outcomes by strengthening the anti-tumor potential of monotreatment against cancer and cancer stem cells,mitigating their toxic adverse effects,and ultimately overcoming resistance.Recently,there has been growing interest in combining natural products from different sources or with clinically used chemotherapeutics to further improve treatment efficacy and tolerability.Thymoquinone(TQ),the main bioactive constituent of Nigella sativa,has gained great attention in combination therapy research after demonstrating its low toxicity to normal cells and remarkable anticancer efficacy in extensive preclinical studies in addition to its ability to target chemoresistant CSCs.Here,we provide an overview of the therapeutic responses resulting from combining TQ with conventional therapeutic agents such as alkylating agents,antimetabolites and antimicrotubules as well as with topoisomerase inhibitors and non-coding RNA.We also review data on anticancer effects of TQ when combined with ionizing radiation and several natural products such as vitamin D3,melatonin and other compounds derived from Chinese medicinal plants.The focus of this review is on two outcomes of TQ combination therapy,namely eradicating CSCs and treating various types of cancers.In conclusion,the ability of TQ to potentiate the anticancer activity of many chemotherapeutic agents and sensitize cancer cells to radiotherapy makes it a promising molecule that could be used in combination therapy to overcome resistance to standard chemotherapeutic agents and reduce their associated toxicities.

Micelles as potential drug delivery systems for colorectal cancer treatment

Despite the significant progress in cancer therapy,colorectal cancer(CRC)remains one of the most fatal malignancies worldwide.Chemotherapy is currently the mainstay therapeutic modality adopted for CRC treatment.However,the long-term effectiveness of chemotherapeutic drugs has been hampered by their low bioavailability,non-selective tumor targeting mechanisms,non-specific biodistribution associated with low drug concentrations at the tumor site and undesirable side effects.Over the last decade,there has been increasing interest in using nanotechnology-based drug delivery systems to circumvent these limitations.Various nanoparticles have been developed for delivering chemotherapeutic drugs among which polymeric micelles are attractive candidates.Polymeric micelles are biocompatible nanocarriers that can bypass the biological barriers and preferentially accumulate in tumors via the enhanced permeability and retention effect.They can be easily engineered with stimuli-responsive and tumor targeting moieties to further ensure their selective uptake by cancer cells and controlled drug release at the desirable tumor site.They have been shown to effectively improve the pharmacokinetic properties of chemotherapeutic drugs and enhance their safety profile and anticancer efficacy in different types of cancer.Given that combination therapy is the new strategy implemented in cancer therapy,polymeric micelles are suitable for multidrug delivery and allow drugs to act concurrently at the action site to achieve synergistic therapeutic outcomes.They also allow the delivery of anticancer genetic material along with chemotherapy drugs offering a novel approach for CRC therapy.Here,we highlight the properties of polymeric micelles that make them promising drug delivery systems for CRC treatment.We also review their application in CRC chemotherapy and gene therapy as well as in combination cancer chemotherapy.