Mitochondrial dysfunction, autophagy stimulation and non-apoptotic cell death caused by nitric oxide-inducing Pt-coated Au nanoparticle in human lung carcinoma cells

• Published in: Biochimica et biophysica acta. General subjects Vol. 1864; no. 1; p. 129452
• Main Authors: Akhtar, Mohd Javed, Ahamed, Maqusood, Alhadlaq, Hisham A., Kumar, Sudhir, Alrokayan, Salman A.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.01.2020
• Subjects: Anticancer; apoptosis; Autophagy; carcinoma; caspase-3; cell viability; cisplatin; cytotoxicity; dihydroethidium; gold; humans; hydrogen peroxide; inhibitory concentration 50; lactate dehydrogenase; lung neoplasms; lungs; mitochondria; nanogold; Necrosis; neoplasm cells; Nitric oxide; platinum; reactive nitrogen species; ROS; superoxide anion; therapeutics; thiobarbituric acid; thiobarbituric acid-reactive substances; Anticancer; Autophagy; Nitric oxide; ROS; Necrosis
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2019.129452

Reactive oxygen species (ROS)-mediated cancer therapeutic has been at higher appreciation than those mediated by reactive nitrogen species. Cytotoxic mechanism of a novel nitric oxide (NO) inducing-Pt coated Au nanoparticle (NP) has been comparatively studied with the well-established ROS inducing Pt-based anticancer drug cisplatin in human lung A549 carcinoma cells. Cytotoxicity was evaluated by MTT assay, lactate dehydrogenase (LDH) release, thiobarbituric acid substances (TBARS) and C11-Boron dipyrromethene (BODIPY). ROS (O2·− and H2O2) was measured with dihydroethidium (DHE) and H2O2-specific sensor. Nitric oxide (NO) and mitochondrial dysfunction were evaluated respectively by NO-specific probe DAR-1 and JC-1. Autophagy was determined by lysotracker (LTR) and monodansylcadaverine (MDC) applied tandemly whereas apoptosis/necrosis by Hoechst/PI and caspase 3 activity. IC50 (concentration that inhibited cell viability by 50%) of Pt coated Au NP came to be 0.413 μM whereas IC50 of cisplatin came out to 86.5 μM in A549 cells treated for 24 h meaning NPs toxicity was over 200 times higher than cisplatin. However, no significant stimulation of intracellular ROS was observed at the IC50 of Pt coated Au NPs in A549 cells. However, markers like LDH release, TBARS, BODIPY and ROS were significantly higher due to cisplatin in comparison to Pt coated Au NP. Pt coated Au NP caused NO-dependent mitochondrial dysfunction and autophagy. Mode of cell death due to NP was much different from ROS-inducing cisplatin. Pt coated Au NP offer promising opportunity in cancer therapeutic and warrants advanced study in vivo models of cancer. [Display omitted] •Pt-coated NPs caused over 200 times higher cytotoxicity in A549 cells than cisplatin.•ROS (O2·− and H2O2) induced by cisplatin was significantly higher than that by Pt coated Au NPs at IC50s.•NO (nitric oxide) induced by Pt-coated Au NPs was significantly higher than that by cisplatin at IC50s.•Induced MOMP and autophagy was significant higher due to Pt coated NP than cisplatin at IC50s.•Cell death was apoptosis-independent by Pt coated Au NPs whereas it was apoptosis-dependent by cisplatin.