Abstract:Palladium nanoparticles (PdNPs) are increasingly being used in medical and biological applications due to their unique physical and chemical properties. Recent evidence suggests that these nanoparticles can act as both a pro-oxidant and as an antioxidant. Melatonin (MLT), which also shows pro- and antioxidant properties, can enhance the efficacy of chemotherapeutic agents when combined with anticancer drugs. Nevertheless, studies regarding the molecular mechanisms underlying the anticancer effects of PdNPs and… Show more
“…Purification and characterization were carried out according to a previously described method. 38 Detailed methodology given as Supplementary File .…”
Section: Methodsmentioning
confidence: 99%
“… 40 , 42 Lipid hydroperoxide and 8-isoprostane levels were also measured as previously described. 38 , 43 …”
Section: Methodsmentioning
confidence: 99%
“…THP-1 cells were treated with PdNPs (15 µM), CSP (10 µM), or GW4869 (20 µM) and incubated for 24 h. Afterward, 4-hydroxynonenal (HNE), 8-OHDG, and 8-OHG levels were determined as previously described 38 , 40 and per the assay kits manufacturer’s instructions (Trevigen, Gaithersburg, MD, USA).…”
Background
Exosomes are endosome-derived nano-sized vesicles that have emerged as important mediators of intercellular communication and play significant roles in various diseases. However, their applications are rigorously restricted by the limited secretion competence of cells. Therefore, strategies to enhance the production and functions of exosomes are warranted. Studies have shown that nanomaterials can significantly enhance the effects of cells and exosomes in intercellular communication; however, how palladium nanoparticles (PdNPs) enhance exosome release in human leukemia monocytic cells (THP-1) remains unclear. Therefore, this study aimed to address the effect of PdNPs on exosome biogenesis and release in THP-1 cells.
Methods
Exosomes were isolated by ultracentrifugation and ExoQuick
TM
and characterized by dynamic light scattering, nanoparticle tracking analysis system, scanning electron microscopy, transmission electron microscopy, EXOCET
TM
assay, and fluorescence polarization. The expression levels of exosome markers were analyzed via quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay.
Results
PdNP treatment enhanced the biogenesis and release of exosomes by inducing oxidative stress, endoplasmic reticulum stress, apoptosis, and immunomodulation. The exosomes were spherical in shape and had an average diameter of 50–80 nm. Exosome production was confirmed via total protein concentration, exosome counts, acetylcholinesterase activity, and neutral sphingomyelinase activity. The expression levels of TSG101, CD9, CD63, and CD81 were significantly higher in PdNP-treated cells than in control cells. Further, cytokine and chemokine levels were significantly higher in exosomes isolated from PdNP-treated THP-1 cells than in those isolated from control cells. THP-1 cells pre-treated with N-acetylcysteine or GW4869 showed significant decreases in PdNP-induced exosome biogenesis and release.
Conclusion
To our knowledge, this is the first study showing that PdNPs stimulate exosome biogenesis and release and simultaneously increase the levels of cytokines and chemokines by modulating various physiological processes. Our findings suggest a reasonable approach to improve the production of exosomes for various therapeutic applications.
“…Purification and characterization were carried out according to a previously described method. 38 Detailed methodology given as Supplementary File .…”
Section: Methodsmentioning
confidence: 99%
“… 40 , 42 Lipid hydroperoxide and 8-isoprostane levels were also measured as previously described. 38 , 43 …”
Section: Methodsmentioning
confidence: 99%
“…THP-1 cells were treated with PdNPs (15 µM), CSP (10 µM), or GW4869 (20 µM) and incubated for 24 h. Afterward, 4-hydroxynonenal (HNE), 8-OHDG, and 8-OHG levels were determined as previously described 38 , 40 and per the assay kits manufacturer’s instructions (Trevigen, Gaithersburg, MD, USA).…”
Background
Exosomes are endosome-derived nano-sized vesicles that have emerged as important mediators of intercellular communication and play significant roles in various diseases. However, their applications are rigorously restricted by the limited secretion competence of cells. Therefore, strategies to enhance the production and functions of exosomes are warranted. Studies have shown that nanomaterials can significantly enhance the effects of cells and exosomes in intercellular communication; however, how palladium nanoparticles (PdNPs) enhance exosome release in human leukemia monocytic cells (THP-1) remains unclear. Therefore, this study aimed to address the effect of PdNPs on exosome biogenesis and release in THP-1 cells.
Methods
Exosomes were isolated by ultracentrifugation and ExoQuick
TM
and characterized by dynamic light scattering, nanoparticle tracking analysis system, scanning electron microscopy, transmission electron microscopy, EXOCET
TM
assay, and fluorescence polarization. The expression levels of exosome markers were analyzed via quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay.
Results
PdNP treatment enhanced the biogenesis and release of exosomes by inducing oxidative stress, endoplasmic reticulum stress, apoptosis, and immunomodulation. The exosomes were spherical in shape and had an average diameter of 50–80 nm. Exosome production was confirmed via total protein concentration, exosome counts, acetylcholinesterase activity, and neutral sphingomyelinase activity. The expression levels of TSG101, CD9, CD63, and CD81 were significantly higher in PdNP-treated cells than in control cells. Further, cytokine and chemokine levels were significantly higher in exosomes isolated from PdNP-treated THP-1 cells than in those isolated from control cells. THP-1 cells pre-treated with N-acetylcysteine or GW4869 showed significant decreases in PdNP-induced exosome biogenesis and release.
Conclusion
To our knowledge, this is the first study showing that PdNPs stimulate exosome biogenesis and release and simultaneously increase the levels of cytokines and chemokines by modulating various physiological processes. Our findings suggest a reasonable approach to improve the production of exosomes for various therapeutic applications.
“…The combination effect increased mitochondria-mediated stress and apoptosis, which was confirmed by the increased expression levels of apoptotic genes. 42 The antiproliferative and antitumor effects of MLT were investigated in B16-F10 cell murine melanoma models. MLT reduced the growth rate and migration of B16-F10 cells, induced G2/M cell cycle arrest, and altered cytoskeletal organization.…”
Section: Role and Therapeutic Potential Of Mlt In Lung Cancermentioning
confidence: 99%
“… 45 MLT directly reduces osteoclast differentiation, bone resorption activity and promotes apoptosis of mature osteoclasts and also MLT inhibits RANKL production in lung and prostate cancer cells by downregulating the p38 MAPK pathway 46 Recently, we have shown that combination of MLT and retinoic acid induced cytotoxicity and apoptosis in human lung epithelial adenocarcinoma cells A549 and H1229 by enhancing oxidative stress and decreasing mitochondrial dysfunctions. 42 Figure 3 Tumor suppressive properties of MLT on lung cancer by targeting family of transcription factors. …”
Section: Role and Therapeutic Potential Of Mlt In Lung Cancermentioning
Cancer is a large group of diseases and the second leading cause of death worldwide. Lung, prostate, colorectal, stomach, and liver cancers are the most common types of cancer in men, whereas breast, colorectal, lung, cervical, and thyroid cancers are the most common among women. Presently, various treatment strategies, including surgical resection combined with chemotherapy, radiotherapy, nanotherapy, and immunotherapy, have been used as conventional treatments for patients with cancer. However, the clinical outcomes of advanced-stage disease remain relatively unfavorable owing to the emergence of chemoresistance, toxicity, and other undesired detrimental side effects. Therefore, new therapies to overcome these limitations are indispensable. Recently, there has been considerable evidence from experimental and clinical studies suggesting that melatonin can be used to prevent and treat cancer. Studies have confirmed that melatonin mitigates the pathogenesis of cancer by directly affecting carcinogenesis and indirectly disrupting the circadian cycle. Melatonin (MLT) is nontoxic and exhibits a range of beneficial effects against cancer via apoptotic, antiangiogenic, antiproliferative, and metastasis-inhibitory pathways. The combination of melatonin with conventional drugs improves the drug sensitivity of cancers, including solid and liquid tumors. In this manuscript, we will comprehensively review some of the cellular, animal, and human studies from the literature that provide evidence that melatonin has oncostatic and anticancer properties. Further, this comprehensive review compiles the available experimental and clinical data analyzing the history, epidemiology, risk factors, therapeutic effect, clinical significance, of melatonin alone or in combination with chemotherapeutic agents or radiotherapy, as well as the underlying molecular mechanisms of its anticancer effect against lung, breast, prostate, colorectal, skin, liver, cervical, and ovarian cancers. Nonetheless, in the interest of readership clarity and ease of reading, we have discussed the overall mechanism of the anticancer activity of melatonin against different types of cancer. We have ended this report with general conclusions and future perspectives.
Given its antioxidant, anti‐inflammatory, and antiapoptotic properties, melatonin (MEL), a health‐caring food to improve sleep disorders, is hypothesized to protect against nanomaterial exposure‐induced toxicity. However, the conclusion derived from different studies seemed inconsistent. A meta‐analysis of all available preclinical studies was performed to examine the effects of MEL on nanomaterial‐induced damages. Eighteen relevant studies were retrieved through searching five electronic databases up to December 2023. The meta‐analysis showed that relative to control, MEL treatment significantly increased cell viability (standardized mean difference [SMD = 1.27]) and alleviated liver function (lowered AST [SMD = −3.89] and ALT [SMD = −5.89]), bone formation (enhanced BV/TV [SMD = 4.13] and lessened eroded bone surface [SMD = −5.40]), and brain nerve (inhibition of AChE activity [SMD = −3.60]) damages in animals. The protective mechanisms of MEL against damages caused by nanomaterial exposure were associated with its antiapoptotic (decreased Bax/Bcl‐2 ratio [SMD = −4.50] and caspase‐3 levels [dose <100 μM: SMD = −3.66]), antioxidant (decreased MDA [in vitro: SMD = −2.84; in vivo: SMD = −4.27]), and anti‐inflammatory (downregulated TNF‐α [in vitro: SMD = −5.41; in vivo: SMD = −3.21] and IL‐6 [in vitro: SMD = −5.90; in vivo: SMD = −2.81]) capabilities. In conclusion, our study suggests that MEL should be supplemented to prevent damages in populations exposed to nanomaterials.
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