Zinc oxide nanoparticles induce oxidative and proteotoxic stress in ovarian cancer cells and trigger apoptosis independent of p53-mutation status

Padmanabhan, Achuth; Kaushik, Mahima; Niranjan, Richa; Richards, JoAnne S.; Ebright, Brandon; Venkatasubbu, G. Devanand

doi:10.1016/j.apsusc.2019.05.099

Cited by 53 publications

(26 citation statements)

References 44 publications

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“…Ovarian cancer remains the most fatal of all gynecological cancers and the leading cause of cancer-related mortality in women. Oxidative and proteotoxic stress by ZnO NPs initiating apoptosis was evaluated on ovarian cancer cell lines and it was demonstrated that their viability considerably dropped with increased cytotoxicity as the size of NPs decreased [ 220 ]. In a study, the cytotoxic effect of ZnO NPs was investigated on human ovarian cancer cells (SKOV 3).…”

Section: In Vitro and In Vivo Anticancerous Activity Of Zno Npsmentioning

confidence: 99%

Recent Advances in Zinc Oxide Nanoparticles (ZnO NPs) for Cancer Diagnosis, Target Drug Delivery, and Treatment

Anjum

Hashim

Malik

et al. 2021

Cancers

246

102

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Cancer is regarded as one of the most deadly and mirthless diseases and it develops due to the uncontrolled proliferation of cells. To date, varieties of traditional medications and chemotherapies have been utilized to fight tumors. However, their immense drawbacks, such as reduced bioavailability, insufficient supply, and significant adverse effects, make their use limited. Nanotechnology has evolved rapidly in recent years and offers a wide spectrum of applications in the healthcare sectors. Nanoscale materials offer strong potential for curing cancer as they pose low risk and fewer complications. Several metal oxide NPs are being developed to diagnose or treat malignancies, but zinc oxide nanoparticles (ZnO NPs) have remarkably demonstrated their potential in the diagnosis and treatment of various types of cancers due to their biocompatibility, biodegradability, and unique physico-chemical attributes. ZnO NPs showed cancer cell specific toxicity via generation of reactive oxygen species and destruction of mitochondrial membrane potential, which leads to the activation of caspase cascades followed by apoptosis of cancerous cells. ZnO NPs have also been used as an effective carrier for targeted and sustained delivery of various plant bioactive and chemotherapeutic anticancerous drugs into tumor cells. In this review, at first we have discussed the role of ZnO NPs in diagnosis and bio-imaging of cancer cells. Secondly, we have extensively reviewed the capability of ZnO NPs as carriers of anticancerous drugs for targeted drug delivery into tumor cells, with a special focus on surface functionalization, drug-loading mechanism, and stimuli-responsive controlled release of drugs. Finally, we have critically discussed the anticancerous activity of ZnO NPs on different types of cancers along with their mode of actions. Furthermore, this review also highlights the limitations and future prospects of ZnO NPs in cancer theranostic.

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Section: In Vitro and In Vivo Anticancerous Activity Of Zno Npsmentioning

confidence: 99%

Recent Advances in Zinc Oxide Nanoparticles (ZnO NPs) for Cancer Diagnosis, Target Drug Delivery, and Treatment

Anjum

Hashim

Malik

et al. 2021

Cancers

246

102

View full text Add to dashboard Cite

show abstract

“…Another proposed method to aid ovarian cancer treatment was to use metal oxide nanoparticles, including zinc oxide nanoparticles (ZnO-NPs), which show promise as anticancer agents. In research on cell lines by Padmanabhan et al [159], ZnO-NPs were found to exhibit toxicity toward ovarian cancer cells, independent of the p53 mutation status of the malignant cells of patients with ovarian cancer. ZnO-NPs induced oxidative and proteotoxic stress in ovarian cancer cells and caused cancer cell death via apoptosis.…”

Section: Ovarian Cancermentioning

confidence: 99%

The Role of Zinc and Copper in Gynecological Malignancies

Michalczyk

Cymbaluk‐Płoska

2020

Nutrients

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Zinc (Zn) and copper (Cu) are essential microelements, which take part in cellular metabolism, feature in enzymatic systems, and regulate enzyme activity. Homeostasis of these micronutrients is tightly regulated by multiple compensatory mechanisms that balance their concentrations including transporters, importers, and metallothioneins. An altered intake of only one of these trace elements may cause an imbalance in their levels and result in their competition for absorption. Relatively low levels of zinc and increased levels of copper may result in an increased level of oxidative stress and impair the antioxidant properties of multiple enzymes. Altered levels of trace elements were discovered in various pathologies including immunological, degenerative, and inflammatory diseases. Moreover, due to the role of Zn and Cu in oxidative stress and chronic inflammation, they were found to influence cancerogenesis. We review the roles of zinc and copper and their mechanisms in tumor growth, metastasis potential, microenvironment remodeling, and drug resistance. We highlight their role as potential biomarkers for cancer diagnosis, treatment, and prognosis, concentrating on their impact on gynecological malignancies.

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“…ZnO-NP promotes proteotoxic and oxidative stress and induces the apoptosis of ovarian cancer cells in a p53-mutation-dependent manner[ 27 ]. ZnO-NP enhances the cell death of multiple human myelomas by regulating reactive oxygen species and cytochrome c/apoptotic protease activating factor 1/caspase-9 signaling[ 28 ]. ZnO-NP increases the apoptosis of human ovarian cancer cells[ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Zinc oxide nanoparticles reduce the chemoresistance of gastric cancer by inhibiting autophagy

Miao¹,

Mao²,

Cai³

et al. 2021

WJG

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BACKGROUND Gastric cancer (GC) is a common malignancy that results in a high rate of cancer-related mortality. Cisplatin (DDP)-based chemotherapy is the first-line clinical treatment for GC therapy, but chemotherapy resistance remains a severe clinical challenge. Zinc oxide nanoparticle (ZnO-NP) has been identified as a promising anti-cancer agent, but the function of ZnO-NP in GC development is still unclear. AIM To explore the effect of ZnO-NP on chemotherapy resistance during GC progression. METHODS ZnO-NP was synthesized, and the effect and underlying mechanisms of ZnO-NP on the malignant progression and chemotherapy resistance of GC cells were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, colony formation assays, transwell assays, wound healing assays, flow cytometry, and Western blot analysis in GC cells and DDP-resistant GC cells, and by tumorigenicity analyses in nude mice. RESULTS Our data revealed that ZnO-NP was able to inhibit proliferation, migration, and invasion and induce apoptosis of GC cells. Meanwhile, ZnO-NP significantly reduced the half maximal inhibitory concentration (IC 50 ) of DDP for the inhibition of cell proliferation of DDP-resistant SGC7901/DDP cell lines. Autophagy was increased in DDP-resistant GC cells, as demonstrated by elevated light chain 3-like protein 2 (LC3II)/LC3I and Beclin-1 expression and repressed p62 expression in SGC7901/DDP cells compared to SGC7901 cells. Mechanically, ZnO-NP inhibited autophagy in GC cells and treatment with DDP induced autophagy, which was reversed by ZnO-NP. Functionally, ZnO-NP attenuated the tumor growth of DDP-resistant GC cells in vivo . CONCLUSION We conclude that ZnO-NP alleviates the chemoresistance of GC cells by inhibiting autophagy. Our findings present novel insights into the mechanism by which ZnO-NP regulates the chemotherapy resistance of GC. ZnO-NP may serve as a potential therapeutic candidate for GC treatment. The potential role of ZnO-NP in the clinical treatment of GC needs clarification in future investigations.

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Zinc oxide nanoparticles induce oxidative and proteotoxic stress in ovarian cancer cells and trigger apoptosis independent of p53-mutation status

Cited by 53 publications

References 44 publications

Recent Advances in Zinc Oxide Nanoparticles (ZnO NPs) for Cancer Diagnosis, Target Drug Delivery, and Treatment

Recent Advances in Zinc Oxide Nanoparticles (ZnO NPs) for Cancer Diagnosis, Target Drug Delivery, and Treatment

The Role of Zinc and Copper in Gynecological Malignancies

Zinc oxide nanoparticles reduce the chemoresistance of gastric cancer by inhibiting autophagy

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