Induction of Caspase-Mediated Apoptosis in HepG2 Liver Carcinoma Cells Using Mutagen–Antioxidant Conjugated Self-Assembled Novel Carbazole Nanoparticles and In Silico Modeling Studies

Krishnan Anand, Naeem Sheik Abdul, Terisha Ghazi, Muthusamy Ramesh, Gaurav Gupta, Murtaza M. Tambuwala, Harish Dureja, Sachin Kumar Singh, Dinesh Kumar Chellappan, Kamal Dua, Boomi Pandi, Muthupandian Saravanan, Anil Amichund Chuturgoon

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Abstract

In this study, novel self-assembled carbazole-thiooctanoic acid nanoparticles
(CTNs) were synthesized from amino carbazole (a mutagen) and thiooctanoic acid (an
antioxidant). The nanoparticles were characterized using hyperspectral techniques. Then, the antiproliferative potential of CTNs was determined in HepG2 liver carcinoma cells. This study employed a solvent−antisolvent interaction method to synthesize a spherical CTN of size less than 50 nm. Moreover, CT was subsequently capped to gold nanoparticles (AuNPs) in the additional comparative studies. The CT derivative was synthesized from carbazole and lipoic acid by the amide bond formation reaction using a coupling agent.
Furthermore, it was characterized using infrared (IR), 1 H nuclear magnetic resonance,
dynamic light scattering (DLS), and transmission electron microscopy techniques. The CTcapped gold nanoparticles (CTAuNPs) were prepared from CT, chloroauric acid, and
NaBH4. The CTAuNPs were characterized using ultraviolet−visible, high-resolution TEM, DLS, and Fourier transform IR techniques. The cytotoxicity and apoptosis-inducing ability of both nanoparticles were determined in HepG2 cells. The results demonstrate that CTNs exhibit antiproliferative activity in the cancerous HepG2 cells. Moreover, molecular docking and molecular dynamics studies were
conducted to explore the therapeutic potential of CT against human EGFR suppressor protein to gain more insights into the binding mode of the CT, which may show a significant role in anticancer therapy.
Original languageEnglish
Number of pages13
JournalACS Omega
Early online date21 Dec 2020
DOIs
Publication statusE-pub ahead of print - 21 Dec 2020

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