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Global Translational Medicine ZnO NPs induce apoptosis in MG63 cells

investigated to see if it was linked to the onset of ROS- In cancer cells, autophagy is considered an alternative
mediated DNA damage. The DAPI staining revealed the therapeutic target . Autophagy entails the production of
[37]
typical cell apoptosis in ZnO NPs-treated MG63 cells. It is autophagosomes, which encircle and encapsulate injured
demonstrated that ZnO NPs induced significant changes organelles or cellular detritus before fusing with lysosomes
in cell morphology and DNA damage in MG63 cells. to destroy their contents . Autophagy is defined by the
[38]
Cellular regulations such as apoptotic alterations, cell involvement of LC3 in autophagosomes and the alteration
[39]
proliferation, and cellular responses to cancer treatment of LC3-I to LC3-II . According to Western blot results,
are heavily influenced by members of pro-apoptotic and administration of ZnO NPs in MG63 cells promoted the
anti-apoptotic proteins . A pro-apoptotic member is a conversion of LC3-I to LC3-II in a dose-dependent manner.
[30]
homolog of an anti-apoptotic member which can oppose LC3-II binds to P62, a protein involved in protein trafficking
as a heterodimer . Most of the adaptive mechanisms of to the proteasome and autophagic breakdown of ubiquitinated
[31]
anticancer drugs that induce apoptosis in cancer cells are protein aggregates. When autophagy is defective, p62
[40]
through the induction of pro-apoptotic member’s expression accumulates and is normally destroyed by autophagosomes .
while attenuating the expression of the anti-apoptotic ZnO NPs treatment also reduced the expression of p62 levels
protein. In our study, we discovered that the administration in MG63 cells in this investigation. The effect of ZnO NPs on
of ZnO NPs augmented the modulation of pro-apoptotic apoptosis induction in MG63 could be utilized for conceiving
proteins, including p53, Bax, Caspase-3, Caspase-8, and an alternative chemotherapeutic formulation containing the
Caspase-9, while suppressing the modulation of the anti- currently available anti-cancer drugs to treat osteosarcoma.
apoptotic member Bcl-2. The induction of apoptosis in However, proper in vivo experiments should be carried out to
ZnO NPs-treated MG63 cells may be due to the suppression explore its effect on other biochemical markers.
of Bcl-2. Nuclear fragmentation that precedes the repair of
DNA damage induced the activation of p53 expression in 5. Conclusion
ZnO NPs-treated MG63 cells. The occurrence of cellular We synthesized ZnO NPs from S. xanthocarpum leaves
oxidative stress activated the p53 gene, thereby causing cell extract and investigated their anticancer activities on
cycle arrest and self-mediated apoptosis . Furthermore, human osteosarcoma MG63 cells. Based on our findings,
[32]
increased caspase-3, -8, and -9 levels cause cancer cells ZnO NPs induced ROS-mediated apoptosis and DN
to undergo rapid and permanent apoptosis. In our study, damage in MG63 cells. Furthermore, ZnO NPs influenced
the treatment of MG63 cells with ZnO NPs increased the expression of apoptotic proteins, such as p53, Bax,
the caspase-3, -8, and -9 expressions. As per a previous Bcl-2, caspase-3, -8, and -9. Moreover, ZnO NPs induced
report, when HepG2 cells were treated with ZnO NPs, the apoptosis and autophagy in MG63 cells by inhibiting the
expression of p53 and Bax was notably high, while anti- P13K/AKT/mTOR signaling pathway and increasing the
apoptotic Bcl-2 members were inactivated . conversion of LC3-I to LC3-II. These findings suggest that
[33]
The PI3K/Akt/mTOR signaling cascade is the most ZnO NPs synthesized by S. xanthocarpum could be an
commonly impaired in cancer cells [34]. Most studies effective anticancer formulation to treat osteosarcoma.
conducted on cancer cells found an increase in Akt
protein expression from 50% to 70% due to PI3K/AKT/ Acknowledgments
mTOR signaling . It is shown that a drug that suppresses None.
[35]
the overexpression of PI3K/AKT/mTOR signaling
molecules may be a potent drug for the treatment of Funding
lung cancer. Therefore, we evaluated the effect of ZnO This research did not receive any specific grant from
NPs on the inhibition of PI3K/AKT/mTOR signaling in funding agencies in the public, commercial, or not-for-
the MG63 cells. The PI3Ks consist of three types of lipid profit sectors.
kinases, with class IA PI3Ks being the most frequently
altered in cancer cases. Receptor tyrosine kinases Conflict of interest
activate PI3K, and active PI3K activates AKT further.
AKT activation then phosphorylates downstream PDK1 The authors declare no conflict of interest.
and mTOR molecules, and subsequently activating Author contributions
transcription factors involved in cell survival, growth, and
proliferation . In the present study, ZnO NPs effectively Conceptualization: Agilan Balupillai
[36]
induced apoptosis and autophagy by inhibiting PI3K/Akt/ Data curation: Muthulakshmi Kannaiyan
mTOR signaling pathway. Hence, ZnO NPs are considered Formal analysis: Ernest David, Babujanarthanam
a potent anticancer candidate to treat osteosarcoma. Ranganathan, Vijayanand Selvaraj

Volume 1 Issue 1 (2022) 10 https://doi.org/10.36922/gtm.v1i1.34