Biofilm Impeding AgNPs Target Skin Carcinoma by Inducing Mitochondrial Membrane Depolarization Mediated through ROS Production

Nayak, Debasis; Kumari, Manisha; Rajachandar, Sripathi; Ashe, Sarbani; Thathapudi, Neethi Chandra; Nayak, Bismita

doi:10.1021/acsami.6b11391

Cited by 47 publications

(34 citation statements)

References 57 publications

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“…Alteration in mitochondrial membrane permeability leads to the formation of mitochondrial permeability transition pores (MPTP) which facilitates unchecked inflow of solutes and free radicals inside the cell. This uncontrolled inflow causes increase of osmotic pressure inside the inner mitochondrial complex and thus finally leads to the overall collapse of the mitochondrial membrane which is considered as the initial step for the activation of the intrinsic cell death pathways 64 .…”

Section: Discussionmentioning

confidence: 99%

Oxidative DNA damage induced by ROS-modulating agents with the ability to target DNA: A comparison of the biological characteristics of citrus pectin and apple pectin

Salehi

Behboudi

Kavoosi

2018

Sci Rep

133

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DNA targeting anticancer agents have been very successful in clinic, especially, when used in combinatorial therapy. But unfortunately, they often exhibit high levels of toxicity towards normal cells. Hence, much effort has been put into finding agents with more selectivity, and less toxicity. Pectins are natural polysaccharides, and beneficial nutritional fibers that have attracted attentions due to their antitumor properties. However, their molecular targets, and mechanism of action are widely unknown. Here, we have reported that citrus pectin (CP) and apple pectin (AP) selectively suppress viability in MDA-MB-231, MCF-7 and T47D human Breast cancer cells, while non-toxic to L929 normal cells. Upon CP, and AP treatments, cancer cells’ ROS content increased rapidly, and led to the collapse of the mitochondrial transmembrane potential which functions upstream of the caspase-dependent apoptosis. CP and AP treated cancer cells were also arrested at the S and G1 or G2/M phases of the cell cycle, respectively. Furthermore, mRNA expression of Galectin-3 (a multi-functional lectin involved in cell adhesion, cell cycle, and apoptosis) reduced in both CP and AP treated cells. Growth inhibition of MDA-MB-231 cells by CP, and AP was concomitant with DNA damage (oxidation, and strand breaks). In this context, in an effort to clarify the mechanism of action, we showed that CP, and AP are able to interact with DNA. The strength and mode of DNA binding were established by spectroscopy techniques. We demonstrated that CP, and AP bind to dsDNA by intercalation, and groove binding/partial intercalation, respectively. In conclusion, our findings suggest that CP, and AP induce apoptosis in MDA-MB-231 cells by increasing the release of ROS, which may be related to the mitochondrial apoptosis pathway, and direct interactions with DNA. Our data indicate that these compounds may be potentially useful in cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Oxidative DNA damage induced by ROS-modulating agents with the ability to target DNA: A comparison of the biological characteristics of citrus pectin and apple pectin

Salehi

Behboudi

Kavoosi

2018

Sci Rep

133

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“…ROS generation damages the biofilm’s integrity and architecture by breaking the biofilm biomatrix and its constituent biomolecules. The biofilm matrix contains eDNA, protein and polysaccharides which are easily damaged by ROS action [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Obliteration of bacterial growth and biofilm through ROS generation by facilely synthesized green silver nanoparticles

2017

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Mangifera indica inflorescence aqueous extract was utilized for production of green AgNPs. Synthesized AgNPs were characterized by UV-vis spectrophotometry, XRD, TEM, FESEM and particles size analyzer. AgNPs showed minimum inhibitory concentrations (MICs) of 8 μg ml-1 and 16 μg ml-1 for Gram negative (K. pneumoniae, P. aeruginosa and E. coli) and Gram positive (S. mutans and S. aureus) strains, respectively which was relatively quite low compared to chemically synthesized silver nanoparticles. AgNPs inhibited 80% and 75% biofilms of E. coli and S. mutans respectively as observed quantitatively by crystal violet assay. Qualitative biofilm inhibition was observed using SEM and CLSM. AgNPs adsorbed catheter also resisted the growth of biofilm on its surface displaying its possible future applications. AgNPs interaction with bacteria lead to bacterial membrane damage as observed by SEM and TEM. The membrane damage was confirmed by detecting leakage of proteins and reducing sugars from treated bacterial cells. AgNPs generated ROS on interaction with bacterial cells and this ROS production can be one of the possible reasons for their action. AgNPs exhibited no toxic effect on the cell viability of HeLa cell line.

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“…However, extensive use may lead to side effects such as gastrointestinal irritation, jaw osteonecrosis, hypocalcemia, and inflammatory eye disorders [20,21]. Otto et al indicated that bisphosphonates exhibited a pH-dependent cellular toxicity [22].…”

Section: Discussionmentioning

confidence: 99%

“…The cells that migrated into the scratched area were imaged at 0 and 24 h and the migrated dis-tance was quantified. The migration ratio (%) was calculated as fol-lows: Migration ratio (%) = (original wound width-remaining wound width)/original wound width × 100 [20]. …”

Section: Methodsmentioning

confidence: 99%

Molecular and cellular mechanisms for zoledronic acid-loaded magnesium-strontium alloys to inhibit giant cell tumors of bone

Wang

Zhu

et al. 2018

Acta Biomaterialia

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In clinics, giant cell tumors of bone (GCTB) are removed by surgery. However, the resultant defects in bone still contain aggressive and metastatic GCTB cells that can recruit osteoclasts to damage bone, leading to new GCTB tumor growth and bone damage after tumor surgery. Hence, it is of high demand in developing a material that can not only fill the bone defects as an implant but also inhibit GCTB in the defect area as a therapeutic agent. More importantly, the molecular and cellular mechanism by which such a material inhibits GCTB growth has never been explored. To solve these two problems, we prepared a new biomaterial, the Mg-Sr alloys that were first coated with calcium phosphate and then loaded with a tumor-inhibiting molecule (Zoledronic acid, ZA). Then, by using a variety of molecular and cellular biological assays, we studied how the ZA-loaded alloys induced the death of GCTB cells (derived from patients) and inhibited their growth at the molecular and cellular level. At the cellular level, our results showed that ZA-loaded Mg-Sr alloys not only induced apoptosis and oxidative stress of GCTB cells, and suppressed their induced pre-osteoclast recruitment, but also inhibited their migration. At the molecular level, our data showed that ZA released from the ZA-loaded Mg-Sr alloys could significantly activate the mitochondrial pathway and inhibit the NF-κB pathway in the GCTB cells. Both mechanisms collectively induced GCTB cell death and inhibited GCTB cell growth. This work showed how a biomaterial inhibit tumor growth at the molecular and cellular level, increasing our understanding in the fundamental principle of materials-induced cancer therapy. This work will be interesting to readers in the fields of metallic materials, inorganic materials, biomaterials and cancer therapy.

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Biofilm Impeding AgNPs Target Skin Carcinoma by Inducing Mitochondrial Membrane Depolarization Mediated through ROS Production

Cited by 47 publications

References 57 publications

Oxidative DNA damage induced by ROS-modulating agents with the ability to target DNA: A comparison of the biological characteristics of citrus pectin and apple pectin

Oxidative DNA damage induced by ROS-modulating agents with the ability to target DNA: A comparison of the biological characteristics of citrus pectin and apple pectin

Obliteration of bacterial growth and biofilm through ROS generation by facilely synthesized green silver nanoparticles

Molecular and cellular mechanisms for zoledronic acid-loaded magnesium-strontium alloys to inhibit giant cell tumors of bone

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