Abstract
ABSTRACTThe present study assessed the cytotoxicity of sodium meta-arsenite (SMA) on telomere shortening and cellular apoptosis in human A-549, MDA-MB-231 and U87-MG cancer cell lines. Following 2 weeks of 1 μM SMA treatment, population doubling time (PDT) was significantly (P < .05) increased by the inhibition of cell proliferation in all the cancer cell lines compared to that in untreated controls. Level of telomerase activity by relative-quantitative telomerase repeat amplification protocol was significantly (P < .05) downregulated by SMA treatment with significant (P < .05) decrease of both telomerase reverse transcriptase and telomerase RNA component transcripts, responsible for telomerase activity. A significant (P < .05) shortening of telomeric repeats by telomere restriction fragment analysis was consequently observed in SMA-treated cells. Moreover, high incidence of cells with senescence-associated β-glucosidase activity was observed in SMA-treated cells and some cells were also differentiated into adipocytes probably due to the loss of tumorous characterizations. Cellular apoptosis proven by DNA fragmentation was observed, and intrinsic apoptotic transcripts (BAX, caspase 3 and caspase 9) and stress-related transcripts (p21, HSP70 and HSP90) were significantly (P < .05) increased in three cancer cell lines treated with SMA. Based on the present study, SMA treatment apparently induced a shortening of telomere length and cytotoxicity, such as induction of cell senescence, apoptosis and cell differentiation. Therefore, we conclude that SMA treatment at specific concentration can lead to gradual loss of tumorous characterizations and can be considered as a potential anti-cancer drug for chemotherapy treatment.
Highlights
Malignant tumors or cancers are characterized by their unlimited as well as higher proliferation capacity with uncontrolled cell cycle properties
We preferentially investigated the effect on the shortening of telomeric repeats and telomerase activity in the human A-549 lung adenocarcinoma, MDA-MB-231 breast adenocarcinoma and U87MG brain glioblastoma astrocytoma cells treated with 1 μM sodium meta-arsenite (SMA) during prolonged culture time of up to 2 weeks
The population doubling time (PDT) was 58.5 ± 8.67, 86.5 ± 13.45 and 130.5 ± 15.72 h in the A-549, MDA-MB231 and U87-MG cancer cell lines treated with 1 μM SMA, respectively
Summary
Malignant tumors or cancers are characterized by their unlimited as well as higher proliferation capacity with uncontrolled cell cycle properties. Most of the cancer cells exhibit unlimited cell proliferation capacity under chemically defined conditions even after starving cell-division-promoting molecules (Rozengurt 1983). Besides maintaining an unlimited cell proliferation capacity, cancer cells are distinctly associated with the maintenance of telomeric repeats. In most of the normal somatic cells, the linear chromosomes exhibit serious structural problems and cannot extend the DNA strand, while the last piece of RNA primer on the lagging strand is removed for DNA replication. The telomeric repeats in the normal somatic cells are gradually shortened through each cell division by the end-replication problem (Allsopp et al 1992; Aubert and Lansdorp 2008; Arnoult and Karlseder 2015). The telomeric repeats play a central role in genetic stability and protects the end of chromosomes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
