Titanium dioxide nanotubes conjugated with quercetin function as an effective anticancer agent by inducing apoptosis in melanoma cells

Abstract

Cancer is a leading cause of death throughout the world. Melanoma is a skin cancer with a significant impact on global public health. Application of nanotechnology in the field of cancer diagnosis, drug delivery, imaging and therapy, has the most attractive approach as nanoparticles reach target sites easily due to their unique properties. Previous studies have shown that titanium dioxide nanotubes (TNT) and quercetin are effective anticancer agents. However, conjugated TNT with quercetin (TNT–Qu) as a combinational treatment is unexplored yet. This study is aimed to explore the anticancer activity of TNT, quercetin, and TNT–Qu in B16F10 melanoma skin cancer cells. TNT–Qu significantly inhibited proliferation at 25 µg/mL of IC 50 lower than quercetin (34 µg/mL) and TNT alone (72 µg/mL). TNT–Qu treatment inhibited migration and significantly induced 60.29% apoptosis in melanoma cells when compared to TNT (14.14%) or quercetin (44.86%) alone treatment. Furthermore, quercetin and TNT–Qu decreased the reactive oxygen species and superoxide levels due to quercetin's antioxidant properties. TNT–Qu treatment arrested 55.5% cells in G2/M phase more than quercetin (30.7%) or pristine TNT (3.7%) treatment. The molecular mechanism of TNT–Qu on melanoma cells revealed that it enhanced the cleaved caspase-3 levels and induced more apoptosis than TNT or quercetin alone. Hence, Novel TNT–Qu exhibited enhanced anticancer properties and could be a potential therapeutic combinational molecule for the treatment of skin cancer.

Graphic abstract

Schematic representation of the proposed mechanism of TNT, quercetin and TNT–Qu inducing apoptosis in B16F10 melanoma cells. TNT–Qu enhanced the cleaved caspase-3 and induced caspase-dependent apoptosis. Importantly, it down-regulates the ROS and dysfunctions mitochondria and enhances the DNA fragmentation.

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Acknowledgements

Taif University researchers supporting project number (TURSP-2020/04), Taif University, Taif, Saudi Arabia.

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SG, MC, DL, AS, and MKM conceived the experiment, SG performed the experiments, PBA, MCR interpreted the results. SG, DL, KRR, I and TAT wrote the first version and all authors contributed in improving the manuscript until reaching the final version.

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Correspondence to Inamuddin or Madhava C. Reddy.

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Gulla, S., Lomada, D., Araveti, P.B. et al. Titanium dioxide nanotubes conjugated with quercetin function as an effective anticancer agent by inducing apoptosis in melanoma cells. J Nanostruct Chem (2021). https://doi.org/10.1007/s40097-021-00396-8

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Keywords

  • Titanium dioxide nanotubes
  • B16F10 melanoma cells
  • Quercetin
  • Apoptosis
  • Caspase-3