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Targeted Therapy for Cancer Stem Cells
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Rama Krishna Nimmakayala, Saswati Karmakar, Garima Kaushik, Sanchita Rauth, Srikanth Barkeer, Saravanakumar Marimuthu, Moorthy P. Ponnusamy
Gold nano-rods are better for photothermal therapy to target CSCs since they exhibit localized surface plasmon resonance at near-infrared wavelength. Near-infrared wavelength is relatively less damaging and possesses high penetrability. Gold nanorods can be conjugated with aptamers to specifically target CSCs [110]. Studies also report a higher uptake of gold nanoparticles by CSCs once they are polyelectrolyte conjugated [111, 112]. Researchers have employed this for the targeted killing of CSCs by modifying polyelectrolyte conjugated gold particles with salinomycin. Researchers have integrated these tools further to develop multi-level therapeutic approaches by combining AuNPs loaded with chemotherapeutic drugs and siRNA (for example, against KRAS) in hydrogels or porous silicon. Such strategies can be upgraded further by incorporating porous silicon and modified AuNPs, and DNA origami loaded with different targeted and chemotherapeutic drugs and generating an emulsion system [104, 31, 114]
Antifungal Activity Validation of Wild Plants used in Argentine Ethnomedicine
Published in Mahendra Rai, Shandesh Bhattarai, Chistiane M. Feitosa, Ethnopharmacology of Wild Plants, 2021
Norma Hortensia Álvarez, Laura Noemí Fernandez, Gisela Marisol Seimandi, María Inés Stegmayer, Verónica Eugenia Ruiz, Marcos Gabriel Derita
Thus, setting new routes for the discovery of effective and safe antifungal drugs should be a priority within the health care system (Castelli et al. 2016). The discovery of new alternative, efficient and antifungal drugs with fewer side effects is very slow and remains a challenge. Plants produce metabolites that can inhibit pathogen growth and these compounds have been intensely explored. Natural products can be a source of antifungals and, used in combinatorial therapy, could be an important advance (Butassi et al. 2015). Several proteins, enzymes and metabolic pathways could be targets for the discovery of efficient inhibitor compounds and recently heat shock proteins calcineurin, salinomycin, trehalose biosynthetic pathway and the glyoxylate cycle have been investigated in several fungal species. Transcriptomic and proteomic approaches have advanced antifungal drug discovery and pointed to new important specific-pathogen targets (Butassi et al. 2019). Thus, the development of new antifungal strategies might reduce the therapeutic time and increase the quality of life of patients, the reports of plants used in the folk medicine of different cultures being an important resource to be considered (Svetaz et al. 2010).
Endocrine Glands
Published in Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard, Toxicologic Pathology, 2018
Richard A. Peterson, Sundeep Chandra, Mark J. Hoenerhoff
The adrenal medulla is a less common site of chemically induced nonproliferative lesions, though proliferative lesions of the medulla are common in rodents, especially rats. Scientific literature on acute toxicity and/or nonproliferative lesions of the adrenal medulla is rather limited. Medullary chromaffin cells in rats are susceptible to acute necrosis and cytolysis by salinomycin, followed by regeneration in as little as 24 h (Chen-Pan et al. 1999). Degeneration of the adrenal medulla has been reported in mice administered with ciguatoxin or ciguatoxin-4c (Terao et al. 1991).
Combined using of paclitaxel and salinomycin active targeting nanostructured lipid carriers against non-small cell lung cancer and cancer stem cells
Published in Drug Delivery, 2019
Jianwen Zhou, Mingshuang Sun, Shanshan Jin, Li Fan, Wenquan Zhu, Xiaoyu Sui, Lixin Cao, Chunrong Yang, Cuiyan Han
To improve the cancer cell specificity and alleviate the side effects of small molecular chemotherapy drugs like PTX, numerous papers have been published in the field of nano drug delivery carriers, of which the superior antitumor effect has been validated (Shin et al., 2012; Werner et al., 2013; Chen et al., 2014; Pandey et al., 2015; Fu et al., 2016; Giordano et al., 2017; Zhang et al., 2018). Nevertheless, it has been mentioned that the drug resistance of cancer stem cells (CSCs) could cause the cancer recurrence and metastasis, which leads to the failure of the chemotherapy (Dallas et al., 2009; Heery et al., 2017). In this case, it seems that the optimal plan to confront cancer is to kill the cancer cells and the CSCs at the same time. Salinomycin (Sal) is a CSCs specific drug discovered in recent years (Gupta et al., 2009; Naujokat & Steinhart, 2012). Researches have revealed its definite therapeutic effect against lung CSCs (Arafat et al., 2013). Herein, it seemed that the combination of PTX and Sal to treat NSCLC could kill the cancer cells and the CSCs at the same time (Larzabal et al., 2013). However, as a small molecule drug, Sal often exhibited severe adverse effects like acute renal failure and even death (Story & Doube, 2004; Zhang et al., 2009; Li et al., 2010). Thus the key problem of the combination of the two drugs is how to reduce the adverse effects.
Functionalised nanomaterials for eradication of CSCs, a promising approach for overcoming tumour heterogeneity
Published in Journal of Drug Targeting, 2018
Leila Farahmand, Behrad Darvishi, Malihe Salehi, Sarvnaz Samadi Kouchaksaraei, Keivan Majidzadeh-A
One of the most prominent purposes of applying nanocarriers is to improve different pharmacokinetic aspects of conventional chemotherapeutic agents including poor solubility, low circulation half-life, low specificity to target organ and high toxicity. Perhaps the best example of this group is salinomycin, an effective therapeutic agent against CSCs but, poorly soluble in water and highly toxic in body. Since many CSCs are CD44 + and can be highly interactive with hyaluronic acid [58], Wei et al. designed hyaluronic acid-based nanogels that were loaded with salinomycin. Administration of salinomycin nanogels demonstrated a significant increase in activity of salinomycin both in multi-cellular spheroids and drug-resistant cell cultures [59].
Fisetin Inhibits Autophagy in HepG2 Cells via PI3K/Akt/mTOR and AMPK Pathway
Published in Nutrition and Cancer, 2021
Kiruthika Sundarraj, Azhwar Raghunath, Lakshmikanthan Panneerselvam, Ekambaram Perumal
Since the discovery of Atg genes, the molecular mechanisms of autophagy were studied extensively, however, the role of autophagic markers in fisetin exposed HepG2 cells remains largely unknown. In the event of autophagy, nascent double-membrane vacuoles called autophagosomes (APs) are formed. These APs sequester proteins, damaged organelles, or pathogens for degradation by lysosomal hydrolases (37). The mature APs fuze with lysosomes to form autophagolysosomes (APLs). The process of APL formation coupled with lysosomal degradation is known as autophagic flux. Autophagic flux is the whole process of macroautophagy starting from the incorporation of cellular components within the autophagosome to digest within the autolysosome. Autophagosomes accumulate during both increased and blocked autophagic flux. Our findings demonstrate that fisetin inhibits autophagic flux formation in a dose-dependent manner in HepG2 cells. Fisetin’s effects on autophagic flux were dose-dependent, which corroborated with dose-dependent exertion of anticancer effects (21). Similar inhibition of autophagic flux was elicited by salinomycin in HCC cells (38). Yet another report revealed that salinomycin treatment on breast cancer stem-like/progenitor cells altered autophagic flux and induced apoptosis (39). The data from this study suggest that autophagic flux inhibition may be a key prerequisite for fisetin-induced HepG2 cell death through apoptosis and necroptosis. Our study demonstrated that fisetin is a potent inhibitor of autophagy in HCC. Another natural product, alpha-hederin blocked autophagic flux and promoted NSCLC killing (40). Similarly, autophagy inhibitor chloroquine and inducer rapamycin were shown to inhibit and induce autophagy in HepG2 cells respectively.