Anti-cancer Applications of Titanocene-Functionalised Nanostructured Systems: An Insight into Cell Death Mechanisms

Apoptosis plays many vital roles in maintaining organ homeostasis and represents type I programmed cell death. Programmed cell death happens when the DNA damage is irremediable and has two important pathways, the intrinsic death pathway also known as the mitochondrial pathway, and the extrinsic programmed cell death pathway. Any defects in the regulation of these crucial pathways have been associated with many disorders, most importantly cancer. Therefore, understanding the molecular basis of apoptosis is essential for the treatment of incurable cancer. To date, several anti-cancer drugs have been developed by targeting anti-apoptotic proteins, which are upregulated in many cancers. Nonetheless, a disease progression often time warranted due to the deregulation of several anti or pro-apoptotic proteins which also contribute to drug resistance. Hence, it is important to understand the maintenance and counteraction of apoptosis and improve successful new pharmacological applications of cell death mechanisms for future therapies. This chapter discusses the mechanism of apoptosis and emerging principles of drug resistance in cancer.

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Cytotoxicity and cell death mechanisms induced by the polyamine-vectorized anti-cancer drug F14512 targeting topoisomerase II

Biochemical Pharmacology ◽

10.1016/j.bcp.2011.08.028 ◽

2011 ◽

Vol 82 (12) ◽

pp. 1843-1852 ◽

Cited By ~ 21

Author(s):

Viviane Brel ◽

Jean-Philippe Annereau ◽

Stéphane Vispé ◽

Anna Kruczynski ◽

Christian Bailly ◽

...

Keyword(s):

Cell Death ◽

Topoisomerase Ii ◽

Cancer Drug ◽

Anti Cancer ◽

Cell Death Mechanisms

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Salinomycin induces autophagic cell death in salinomycin-sensitive melanoma cells through inhibition of autophagic flux

Scientific Reports ◽

10.1038/s41598-020-75598-1 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Yajing Liu ◽

Yinghua Hao ◽

Yuxia Li ◽

Yadan Zheng ◽

Jiajing Dai ◽

...

Keyword(s):

Cell Death ◽

Cell Lines ◽

Mrna Level ◽

Melanoma Cells ◽

Autophagic Cell Death ◽

Autophagic Flux ◽

Anti Cancer ◽

Sensitive Line ◽

Cancer Types ◽

Insight Into

Abstract Several literature has shown that salinomycin (Sal) is able to kill various types of cancer cells through different signaling pathways. However, its effect on melanoma has seldom been reported. We examined the anti-cancer efficacy of Sal in melanoma cell lines, and found six of eight cell lines were sensitive to Sal. Given the fact that the roles of Sal are diverse in different cancer types, we were eager to figure out the mechanism involved in the current study. We noticed the most sensitive line, SK-Mel-19, showed a typical morphological change after Sal treatment. The autophagy inhibitor, 3-MA, could effectively suppress Sal-induced cell death. It could also facilitate the increase of autophagic markers and reduce the turnover of autophagosomes, which resulted in an aberrant autophagic flux. On the other hand, Sal could stimulate endoplasmic reticulum stress and cause an accumulation of dysfunctional mitochondria. We also discovered a potential correlation between LC3B mRNA level and its sensitivity to Sal in 43 clinical melanoma samples. Overall, our results indicated that Sal could have multiple effect on melanoma cells and induce autophagic cell death in certain kinds of cells, which provided a new insight into the chemotherapy for melanoma.

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