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Öğe Advances in understanding the role of P-gp in doxorubicin resistance: molecular pathways, therapeutic strategies, and prospects(Elsevier, 2022) Mirzaei, Sepideh; Gholami, Mohammad Hossein; Hashemi, Farid; Zabolian, Amirhossein; Zarrabi, AliP-glycoprotein (P-gp) is a drug efflux transporter that triggers doxorubicin (DOX) resistance. In this review, we highlight the molecular avenues regulating P-gp, such as Nrf2, HIF-1?, miRNAs, and long noncoding (lnc)RNAs, to reveal their participation in DOX resistance. These antitumor compounds and genetic tools synergistically reduce P-gp expression. Furthermore, ATP depletion impairs P-gp activity to enhance the antitumor activity of DOX. Nanoarchitectures, including liposomes, micelles, polymeric nanoparticles (NPs), and solid lipid nanocarriers, have been developed for the co-delivery of DOX with anticancer compounds and genes enhancing DOX cytotoxicity. Surface modification of nanocarriers, for instance with hyaluronic acid (HA), can promote selectivity toward cancer cells. We discuss these aspects with a focus on P-gp expression and activity. © 2021 The Author(s)Öğe Cervical cancer progression is regulated by SOX transcription factors: Revealing signaling networks and therapeutic strategies(Elsevier Science, 2021) Paskeh, Mahshid Deldar Abad; Mirzaei, Sepideh; Gholami, Mohammad Hossein; Zarrabi, Ali; Zabolian, Amirhossein; Hashemi, Mehrdad; Hushmandi, KiavashCervical cancer is the fourth common gynecologic cancer and is considered as second leading cause of death among women. Various strategies are applied in treatment of cervical cancer including radiotherapy, chemotherapy and surgery. However, cervical cancer cells demonstrate aggressive behavior in advanced phases, requiring novel strategies in their elimination. On the other hand, SOX proteins are transcription factors capable of regulating different molecular pathways and their expression varies during embryogenesis, disease development and carcinogenesis. In the present review, our aim is to reveal role of SOX transcription factors in cervical cancer. SOX transcription factors play like a double-edged sword in cancer. For instance, SOX9 possesses both tumor-suppressor and tumor-promoting role in cervical cancer. Therefore, exact role of each SOX members in cervical cancer has been discussed to direct further experiments for revealing other functions. SOX proteins can regulate proliferation and metastasis of cervical cancer cells. Furthermore, response of cervical cancer cells to chemotherapy and radiotherapy is tightly regulated by SOX transcription factors. Different downstream targets of SOX proteins such as Wnt signaling, EMT and Hedgehog have been identified. Besides, upstream mediators such as microRNAs, lncRNAs and circRNAs can regulate SOX expression in cervical cancer. In addition to pre-clinical studies, role of SOX transcription factors as prognostic and diagnostic tools in cervical cancer has been shown.Öğe Correction: The long and short non-coding RNAs modulating EZH2 signaling in cancer (Journal of Hematology & Oncology, (2022), 15, 1, (18), 10.1186/s13045-022-01235-1)(BioMed Central Ltd, 2022) Mirzaei, Sepideh; Gholami, Mohammad Hossein; Hushmandi, Kiavash; Hashemi, Farid; Zabolian, Amirhossein; Canadas, Israel; Zarrabi, Ali; Nabavi, Noushin; Aref, Amir Reza; Crea, Francesco; Wang, Yuzhuo; Ashrafizadeh, Milad; Kumar, Alan PremThe original article [1] contained an error in co-author, Farid Hashemi’s name which has since been corrected. © 2022, The Author(s).Öğe Curcumin and its derivatives in cancer therapy: potentiating antitumor activity of cisplatin and reducing side effects(WILEY, 2021) Abadi, Asal Jalal; Mirzaei, Sepideh; Mahabady, Mahmood Khaksary; Hashemi, Farid; Zabolian, Amirhossein; Hashemi, Fardin; Raee, Pourya; Zarrabi, AliCurcumin is a phytochemical isolated from Curcuma longa with potent tumor-suppressor activity, which has shown significant efficacy in pre-clinical and clinical studies. Curcumin stimulates cell death, triggers cycle arrest, and suppresses oncogenic pathways, thereby suppressing cancer progression. Cisplatin (CP) stimulates DNA damage and apoptosis in cancer chemotherapy. However, CP has adverse effects on several organs of the body, and drug resistance is frequently observed. The purpose of the present review is to show the function of curcumin in decreasing CP's adverse impacts and improving its antitumor activity. Curcumin administration reduces ROS levels to prevent apoptosis in normal cells. Furthermore, curcumin can inhibit inflammation via down-regulation of NF-kappa B to maintain the normal function of organs. Curcumin and its nanoformulations can reduce the hepatoxicity, neurotoxicity, renal toxicity, ototoxicity, and cardiotoxicity caused by CP. Notably, curcumin potentiates CP cytotoxicity via mediating cell death and cycle arrest. Besides, curcumin suppresses the STAT3 and NF-kappa B as tumor-promoting pathways, to enhance CP sensitivity and prevent drug resistance. The targeted delivery of curcumin and CP to tumor cells can be mediated nanostructures. In addition, curcumin derivatives are also able to reduce CP-mediated side effects, and increase CP cytotoxicity against various cancer types.Öğe Doxorubicin-loaded graphene oxide nanocomposites in cancer medicine: stimuli-responsive carriers, co-delivery and suppressing resistance(2022) Ashrafizadeh, Milad; Saebfar, Hamidreza; Gholami, Mohammad Hossein; Hushmandi, Kiavash; Zabolian, Amirhossein; Zarrabi, AliIntroduction: The application of doxorubicin (DOX) in cancer therapy has been limited due to its drug resistance and poor internalization. Graphene oxide (GO) nanostructures have the capacity for DOX delivery while promoting its cytotoxicity in cancer. Areas covered: The favorable characteristics of GO nanocomposites, preparation method, and application in cancer therapy are described. Then, DOX resistance in cancer is discussed. The GO-mediated photothermal therapy and DOX delivery for cancer suppression are described. Preparation of stimuli-responsive GO nanocomposites, surface functionalization, hybrid nanoparticles, and theranostic applications are emphasized in DOX chemotherapy. Expert opinion: Graphene oxide nanoparticle-based photothermal therapy maximizes the anti-cancer activity of DOX against cancer cells. Apart from DOX delivery, GO nanomaterials are capable of loading anti-cancer agents and genetic tools to minimize drug resistance and enhance the cytolytic impact of DOX in cancer eradication. To enhance DOX accumulation in cancer cells, stimuli-responsive (redox-, light-, enzyme- and pH-sensitive) GO nanoparticles have been developed for DOX delivery. Further development of targeted delivery of DOX-loaded GO nanomaterials against cancer cells may be achieved by surface modification of polymers such as polyethylene glycol, hyaluronic acid, and chitosan. Doxorubicin-loaded GO nanoparticles have demonstrated theranostic potential for simultaneous diagnosis and therapy. Hybridization of GO with other nanocarriers such as silica and gold nanoparticles further broadens their potential anti-cancer therapy applications.Öğe Emerging role of exosomes in cancer progression and tumor microenvironment remodeling(BioMed Central, 2022) Paskeh, Mahshid Deldar Abad; Entezari, Maliheh; Mirzaei, Sepideh; Zabolian, Amirhossein; Zarrabi, AliCancer is one of the leading causes of death worldwide, and the factors responsible for its progression need to be elucidated. Exosomes are structures with an average size of 100 nm that can transport proteins, lipids, and nucleic acids. This review focuses on the role of exosomes in cancer progression and therapy. We discuss how exosomes are able to modulate components of the tumor microenvironment and influence proliferation and migration rates of cancer cells. We also highlight that, depending on their cargo, exosomes can suppress or promote tumor cell progression and can enhance or reduce cancer cell response to radio- and chemo-therapies. In addition, we describe how exosomes can trigger chronic inflammation and lead to immune evasion and tumor progression by focusing on their ability to transfer non-coding RNAs between cells and modulate other molecular signaling pathways such as PTEN and PI3K/Akt in cancer. Subsequently, we discuss the use of exosomes as carriers of anti-tumor agents and genetic tools to control cancer progression. We then discuss the role of tumor-derived exosomes in carcinogenesis. Finally, we devote a section to the study of exosomes as diagnostic and prognostic tools in clinical courses that is important for the treatment of cancer patients. This review provides a comprehensive understanding of the role of exosomes in cancer therapy, focusing on their therapeutic value in cancer progression and remodeling of the tumor microenvironment. Graphical Abstract: [Figure not available: see fulltext.]. © 2022, The Author(s).Öğe EZH2 as a new therapeutic target in brain tumors: Molecular landscape, therapeutic targeting and future prospects(Elsevier, 2022) Paskeh, Mahshid Deldar Abad; Mehrabi, Atefeh; Gholami, Mohammad Hossein; Zabolian, Amirhossein; Ranjbar, Ehsan; Zarrabi, AliBrain tumors are responsible for high mortality and morbidity worldwide. The brain tumor treatment depends on identification of molecular pathways involved in progression and malignancy. Enhancer of zeste homolog 2 (EZH2) has obtained much attention in recent years in field of cancer therapy due to its aberrant expression and capacity in modulating expression of genes by binding to their promoter and affecting methylation status. The present review focuses on EZH2 signaling in brain tumors including glioma, glioblastoma, astrocytoma, ependymomas, medulloblastoma and brain rhabdoid tumors. EZH2 signaling mainly participates in increasing proliferation and invasion of cancer cells. However, in medulloblastoma, EZH2 demonstrates tumor-suppressor activity. Furthermore, EZH2 can regulate response of brain tumors to chemotherapy and radiotherapy. Various molecular pathways can function as upstream mediators of EZH2 in brain tumors including lncRNAs and miRNAs. Owing to its enzymatic activity, EZH2 can bind to promoter of target genes to induce methylation and affects their expression. EZH2 can be considered as an independent prognostic factor in brain tumors that its upregulation provides undesirable prognosis. Both anti-tumor agents and gene therapies such as siRNA have been developed for targeting EZH2 in cancer therapy.Öğe The long and short non-coding RNAs modulating EZH2 signaling in cancer(2022) Mirzaei, Sepideh; Gholami, Mohammad Hossein; Hushmandi, Kiavash; Hshemi, Farid; Zabolian, Amirhossein; Canadas, Israel; Zarrabi, Ali; Nabavi, Noushin; Aref, Amir Reza; Crea, Francesco; Wang, Yuzhuo; Ashrafizadeh, Milad; Kumar, Alan PremNon-coding RNAs (ncRNAs) are a large family of RNA molecules with no capability in encoding proteins. However, they participate in developmental and biological processes and their abnormal expression affects cancer progression. These RNA molecules can function as upstream mediators of different signaling pathways and enhancer of zeste homolog 2 (EZH2) is among them. Briefly, EZH2 belongs to PRCs family and can exert functional roles in cells due to its methyltransferase activity. EZH2 affects gene expression via inducing H3K27me3. In the present review, our aim is to provide a mechanistic discussion of ncRNAs role in regulating EZH2 expression in different cancers. MiRNAs can dually induce/inhibit EZH2 in cancer cells to affect downstream targets such as Wnt, STAT3 and EMT. Furthermore, miRNAs can regulate therapy response of cancer cells via affecting EZH2 signaling. It is noteworthy that EZH2 can reduce miRNA expression by binding to promoter and exerting its methyltransferase activity. Small-interfering RNA (siRNA) and short-hairpin RNA (shRNA) are synthetic, short ncRNAs capable of reducing EZH2 expression and suppressing cancer progression. LncRNAs mainly regulate EZH2 expression via targeting miRNAs. Furthermore, lncRNAs induce EZH2 by modulating miRNA expression. Circular RNAs (CircRNAs), like lncRNAs, affect EZH2 expression via targeting miRNAs. These areas are discussed in the present review with a focus on molecular pathways leading to clinical translation.Öğe Long non-coding RNAs and exosomal incRNAs: Potential functions in lung cancer progression, drug resistance and tumor microenvironment remodeling(Elsevier Science, 2022) Entezari, Maliheh; Ghanbarirad, Maryam; Taheriazam, Afshin; Sadrkhanloo, Mehrdokht; Zabolian, Amirhossein; Shekhi Beig Goharrizi, Mohammad Ali; Hushmandi, Kiavash; Aref, Amir Reza; Ashrafizadeh, Milad; Zarrabi, Ali; Nabavi, Noushin; Rabiee, Navid; Hashemi, Mehrdad; Samarghandian, SaeedAmong the different kinds of tumors threatening human life, lung cancer is one that is commonly observed in both males and females. The aggressive behavior of lung cancer and interactions occurring in tumor microenvironment enhances the malignancy of this tumor. The lung tumor cells have demonstrated capacity in developing chemo- and radio-resistance. LncRNAs are a category of non-coding RNAs that do not encode proteins, but their aberrant expression is responsible for tumor development, especially lung cancer. In the present review, we focus on both lncRNAs and exosomal lncRNAs in lung cancer, and their ability in regulating proliferation and metastasis. Cell cycle progression and molecular mechanisms related to lung cancer metastasis such as EMT and MMPs are regulated by lncRNAs. LncRNAs interact with miRNAs, STAT, Wnt, EZH2, PTEN and PI3K/Akt signaling pathways to affect progression of lung cancer cells. LncRNAs demonstrate both tumor-suppressor and tumor-promoting functions in lung cancer. They can be considered as biomarkers in lung cancer and especially exosomal lncRNAs present in body fluids are potential tools for minimally invasive diagnosis. Furthermore, weÖğe Long non-coding RNAs and exosomal lncRNAs: Potential functions in lung cancer progression, drug resistance and tumor microenvironment remodeling(Elsevier, 2022) Entezari, Maliheh; Ghanbarirad, Maryam; Taheriazam, Afshin; Sadrkhanloo, Mehrdokht; Zabolian, Amirhossein; Goharrizi, Mohammad Ali Shekhi Beig; Hushmandi, Kiavash; Aref, Amir Reza; Ashrafizadeh, Milad; Zarrabi, Ali; Nabavi, Noushin; Rabiee, Navid; Hashemi, Mehrdad; Samarghandian, SaeedAmong the different kinds of tumors threatening human life, lung cancer is one that is commonly observed in both males and females. The aggressive behavior of lung cancer and interactions occurring in tumor microenvironment enhances the malignancy of this tumor. The lung tumor cells have demonstrated capacity in developing chemo- and radio-resistance. LncRNAs are a category of non-coding RNAs that do not encode proteins, but their aberrant expression is responsible for tumor development, especially lung cancer. In the present review, we focus on both lncRNAs and exosomal lncRNAs in lung cancer, and their ability in regulating proliferation and metastasis. Cell cycle progression and molecular mechanisms related to lung cancer metastasis such as EMT and MMPs are regulated by lncRNAs. LncRNAs interact with miRNAs, STAT, Wnt, EZH2, PTEN and PI3K/Akt signaling pathways to affect progression of lung cancer cells. LncRNAs demonstrate both tumor-suppressor and tumor-promoting functions in lung cancer. They can be considered as biomarkers in lung cancer and especially exosomal lncRNAs present in body fluids are potential tools for minimally invasive diagnosis. Furthermore, we discuss regulation of lncRNAs by anti-cancer drugs and genetic tools as well as the role of these factors in therapy response of lung cancer cells.Öğe Long noncoding RNAs: A novel insight in the leukemogenesis and drug resistance in acute myeloid leukemia(Wiley-Blackwell, 2021) Kirtonia, Anuradha; Ashrafizadeh, Milad; Hushmandi, Kiavash; Zabolian, Amirhossein; Bejandi, Atefe K.; Rani, Reshma; Pandey, Amit K.; Baligar, Prakash; Kumar, Vinit; Das, Bhudev C.; Garg, ManojAcute myeloid leukemia (AML) is a common hematological disorder with heterogeneous nature that resulted from blocked myeloid differentiation and an enhanced number of immature myeloid progenitors. During several decades, different factors, including cytogenetic, genetic, and epigenetic have been reported to contribute to the pathogenesis of AML by inhibiting the differentiation and ensuring the proliferation of myeloid blast cells. Recently, long noncoding RNAs (lncRNAs) have been considered as potential diagnostic, therapeutic, and prognostic factors in different human malignancies including AML. Altered expression of lncRNAs is correlated with the transformation of hematopoietic stem and progenitor cells into leukemic blast cells because of their distinct role in the key cellular processes. We discuss the significant role of lncRNAs in the proliferation, survival, differentiation, leukemic stem cells in AML and their involvement in different molecular pathways (insulin-like growth factor type I receptor, FLT3, c-KIT, Wnt, phosphatidylinositol 3-kinase/protein kinase-B, microRNAs), and associated mechanisms such as autophagy, apoptosis, and glucose metabolism. In addition, we aim to highlight the role of lncRNAs as reliable biomarkers for diagnosis, prognosis, and drug resistance for precision medicine in AML.Öğe Nanoliposomes as nonviral vectors in cancer gene therapy(John Wiley and Sons Inc, 2024) Yıldız, Safiye Nur; Entezari, Maliheh; Paskeh, Mahshid Deldar Abad; Mirzaei, Sepideh; Kalbasi, Alireza; Zabolian, Amirhossein; Hashemi, Farid; Hushmandi, Kiavash; Hashemi, Mehrdad; Raei, Mehdi; Goharrizi, Mohammad Ali Sheikh Beig; Aref, Amir Reza; Zarrabi, Ali; Ren, Jun; Orive, Gorka; Rabiee, Navid; Ertaş, Yavuz NuriNonviral vectors, such as liposomes, offer potential for targeted gene delivery in cancer therapy. Liposomes, composed of phospholipid vesicles, have demonstrated efficacy as nanocarriers for genetic tools, addressing the limitations of off-targeting and degradation commonly associated with traditional gene therapy approaches. Due to their biocompatibility, stability, and tunable physicochemical properties, they offer potential in overcoming the challenges associated with gene therapy, such as low transfection efficiency and poor stability in biological fluids. Despite these advancements, there remains a gap in understanding the optimal utilization of nanoliposomes for enhanced gene delivery in cancer treatment. This review delves into the present state of nanoliposomes as carriers for genetic tools in cancer therapy, sheds light on their potential to safeguard genetic payloads and facilitate cell internalization alongside the evolution of smart nanocarriers for targeted delivery. The challenges linked to their biocompatibility and the factors that restrict their effectiveness in gene delivery are also discussed along with exploring the potential of nanoliposomes in cancer gene therapy strategies by analyzing recent advancements and offering future directions. © 2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.Öğe Noncoding RNAs and their therapeutics in paclitaxel chemotherapy: Mechanisms of initiation, progression, and drug sensitivity(Wiley, 2022) Mahabady, Mahmood K.; Mirzaei, Sepideh; Saebfar, Hamidreza; Gholami, Mohammad H.; Zabolian, Amirhossein; Hushmandi, Kiavash; Hashemi, Farid; Tajik, Fatemeh; Hashemi, Mehrdad; Kumar, Alan P.; Aref, Amir R.; Zarrabi, Ali; Khan, Haroon; Hamblin, Michael R.; Ertas, Yavuz Nuri; Samarghandian, SaeedThe identification of agents that can reverse drug resistance in cancer chemotherapy, andenhance the overall efficacy is of great interest. Paclitaxel (PTX) belongs to taxane family hat exerts an antitumor effect by stabilizing microtubules and inhibiting cell cycleprogression. However, PTX resistance often develops in tumors due to the over-expression of drug transporters and tumor?promoting pathways. Noncoding RNAs(ncRNAs) are modulators of many processes in cancer cells, such as apoptosis, migration,differentiation, and angiogenesis. In the present study, we summarize the effects ofncRNAs on PTX chemotherapy. MicroRNAs (miRNAs) can have opposite effects on PTXresistance (stimulation or inhibition) via influencing YES1, SK2, MRP1, and STAT3.Moreover, miRNAs modulate the growth and migration rates of tumor cells in regulatingPTX efficacy. PIWI?interacting RNAs, small interfering RNAs, and short?hairpin RNAs areother members of ncRNAs regulating PTX sensitivity of cancer cells. Long noncodingRNAs (LncRNAs) are similar to miRNAs and can modulate PTX resistance/sensitivity bytheir influence on miRNAs and drug efflux transport. The cytotoxicity of PTX againsttumor cells can also be affected by circular RNAs (circRNAs) and limitation is thatoncogenic circRNAs have been emphasized and experiments should also focus on onco?suppressor circRNAs.Öğe Resveratrol Augments Doxorubicin and Cisplatin Chemotherapy: A Novel Therapeutic Strategy(Bentham Science Publ Ltd, 2023) Mirzaei, Sepideh; Gholami, Mohammad Hossein; Zabolian, Amirhossein; Saleki, Hossein; Bagherian, Morteza; Torabi, Seyed Mohammadreza; Sharifzadeh, Seyed OmidBackground The treatment of cancer is a current challenge for public health, causing high rates of morbidity and mortality worldwide. Doxorubicin (DOX) and cisplatin (CP) are two well-known chemotherapeutic agents approved by the Food and Drug Administration to treat cancer patients. However, there are two problems associated with DOX and CP: drug resistance and adverse impact. Resveratrol (Res) belongs to the stilbene class and possesses various health-promoting effects, such as antioxidant, anti-inflammatory, anticancer, hepatoprotective, and neuroprotective effects. Objective The present review aims to give special attention to the therapeutic impacts of Res in potentiating DOX and CP's antitumor activities and reducing their side effects. Methods PubMed, Science Direct, and Google Scholar were used to search articles for the current manuscripts. Results Co-administration of Res can prevent chemoresistance and potentiate the induction of apoptosis and cell cycle arrest in cancer cells. Res can enhance the sensitivity of cancer cells to DOX and CP chemotherapy by inhibiting the migration and metastasis of cancer cells. Simultaneously, Res, due to its therapeutic actions ameliorates the adverse impacts of DOX and CP on normal cells and organs, including the liver, kidney, brain, and testes. As Res suffers from poor bioavailability, nanoformulations have been developed with promising results to improve its antitumor activity and protective effects. Conclusion Based on preclinical studies, it is obvious that Res is a promising adjsuvant for CP and DOX chemotherapy, and its benefits can be utilized in the clinical course.Öğe Resveratrol in breast cancer treatment: from cellular effects to molecular mechanisms of action(Springer Science and Business Media Deutschland GmbH, 2022) Behroozaghdam, Mitra; Dehghani, Maryam; Zabolian, Amirhossein; Kamali, Davood; Javanshir, Salar; Hasani Sadi, Farzaneh; Hashemi, Mehrdad; Tabari, Teimour; Rashidi, Mohsen; Mirzaei, Sepideh; Zarepour, Atefeh; Zarrabi, Ali; De Greef, Danielle; Bishayee, AnupamBreast cancer (BC) is one of the most common cancers in females and is responsible for the highest cancer-related deaths following lung cancer. The complex tumor microenvironment and the aggressive behavior, heterogenous nature, high proliferation rate, and ability to resist treatment are the most well-known features of BC. Accordingly, it is critical to find an effective therapeutic agent to overcome these deleterious features of BC. Resveratrol (RES) is a polyphenol and can be found in common foods, such as pistachios, peanuts, bilberries, blueberries, and grapes. It has been used as a therapeutic agent for various diseases, such as diabetes, cardiovascular diseases, inflammation, and cancer. The anticancer mechanisms of RES in regard to breast cancer include the inhibition of cell proliferation, and reduction of cell viability, invasion, and metastasis. In addition, the synergistic effects of RES in combination with other chemotherapeutic agents, such as docetaxel, paclitaxel, cisplatin, and/or doxorubicin may contribute to enhancing the anticancer properties of RES on BC cells. Although, it demonstrates promising therapeutic features, the low water solubility of RES limits its use, suggesting the use of delivery systems to improve its bioavailability. Several types of nano drug delivery systems have therefore been introduced as good candidates for RES delivery. Due to RES’s promising potential as a chemopreventive and chemotherapeutic agent for BC, this review aims to explore the anticancer mechanisms of RES using the most up to date research and addresses the effects of using nanomaterials as delivery systems to improve the anticancer properties of RES. Graphical abstract: [Figure not available: see fulltext.].Öğe Targeted regulation of autophagy using nanoparticles: New insight into cancer therapy(Elsevier, 2022) Paskeh, Mahshid Deldar Abad; Entezari, Maliheh; Clark, Courtney; Zabolian, Amirhossein; Ranjbar, Ehsan; Zarrabi, AliNormal cells depend on autophagy to maintain cellular homeostasis by recycling damaged organelles and misfolded proteins and degrading toxic agents. Similar to apoptosis, targeting autophagy has been under attention in cancer therapy. However, autophagy has both pro-survival and pro-death functions in tumors, and its targeting requires further elucidation. The current review focuses on using nanoparticles for targeting autophagy in cancer treatment. Nanocarriers can deliver autophagy regulators along with chemotherapeutic agents leading to intracellular accumulation in cancer cells and synergistic cancer therapy. Furthermore, genetic tools such as siRNA and shRNA can be used for targeting molecular components that regulate autophagy, such as the ATG12-ATG5-ATG16L1 complex. A number of nanostructures, such as gold and zinc oxide nanoparticles, can be used to enhance oxidative stress-mediated apoptosis and autophagy, reducing cancer progression. Further, using nanoparticles to modulate autophagy potentiates the anti-tumor effects of cisplatin and gefitinib during chemotherapy. Polymeric nanoparticles, lipid-based nanostructures and carbon-based nanomaterials are among other nanoparticles capable of regulating autophagy in cancer cells. Of note, various regulatory components of autophagy such as ATGs, Beclin-1 and LC3-II can be affected by nanomaterials. Based on the role of nanomaterial-induced autophagy as pro-survival or pro-death, further targeting can potentiate the fight against cancer cells. © 2021 Elsevier B.V.Öğe Targeting cancer stem cells by dietary agents: an important therapeutic strategy against human malignancies(MDPI, 2021) Paskeh, Mahshid Deldar Abad; Asadi, Shafagh; Zabolian, Amirhossein; Saleki, Hossein; Khoshbakht, Mohammad Amin; Zarrabi, AliAs a multifactorial disease, treatment of cancer depends on understanding unique mechanisms involved in its progression. The cancer stem cells (CSCs) are responsible for tumor stemness and by enhancing colony formation, proliferation as well as metastasis, and these cells can also mediate resistance to therapy. Furthermore, the presence of CSCs leads to cancer recurrence and therefore their complete eradication can have immense therapeutic benefits. The present review focuses on targeting CSCs by natural products in cancer therapy. The growth and colony formation capacities of CSCs have been reported can be attenuated by the dietary agents. These compounds can induce apoptosis in CSCs and reduce tumor migration and invasion via EMT inhibition. A variety of molecular pathways including STAT3, Wnt/?-catenin, Sonic Hedgehog, Gli1 and NF-?B undergo down-regulation by dietary agents in suppressing CSC features. Upon exposure to natural agents, a significant decrease occurs in levels of CSC markers including CD44, CD133, ALDH1, Oct4 and Nanog to impair cancer stemness. Furthermore, CSC suppression by dietary agents can enhance sensitivity of tumors to chemotherapy and radiotherapy. In addition to in vitro studies, as well as experiments on the different preclinical models have shown capacity of natural products in suppressing cancer stemness. Furthermore, use of nanostructures for improving therapeutic impact of dietary agents is recommended to rapidly translate preclinical findings for clinical use. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Öğe Targeting Nrf2 in ischemia-reperfusion alleviation: From signaling networks to therapeutic targeting(Elsevier Inc., 2022) Sadrkhanloo, Mehrdokht; Entezari, Maliheh; Orouei, Sima; Zabolian, Amirhossein; Mirzaie, Amirreza; Maghsoudloo, Amin; Raesi, Rasoul; Asadi, Neda; Hashemi, Mehrdad; Zarrabi, Ali; Khan, Haroon; Mirzaei, Sepideh; Samarghandian, SaeedThe nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator of redox balance and it responds to various cell stresses that oxidative stress is the most well-known one. The Nrf2 should undergo nuclear translocation to exert its protective impacts and decrease ROS production. On the other hand, ischemic/reperfusion (I/R) injury is a pathological event resulting from low blood flow to an organ and followed by reperfusion. The I/R induces cell injury and organ dysfunction. The present review focuses on Nrf2 function in alleviation of I/R injury. Stimulating of Nrf2 signaling ameliorates I/R injury in various organs including lung, liver, brain, testis and heart. The Nrf2 enhances activity of antioxidant enzymes to reduce ROS production and prevent oxidative stress-mediated cell death. Besides, Nrf2 reduces inflammation via decreasing levels of pro-inflammatory factors including IL-6, IL-1? and TNF-?. Nrf2 signaling is beneficial in preventing apoptosis and increasing cell viability. Nrf2 induces autophagy to prevent apoptosis during I/R injury. Furthermore, it can interact with other molecular pathways including PI3K/Akt, NF-?B, miRNAs, lncRNAs and GSK-3? among others, to ameliorate I/R injury. The therapeutic agents, most of them are phytochemicals such as resveratrol, berberine and curcumin, induce Nrf2 signaling in I/R injury alleviation. © 2022
