scholarly journals Linalool Induces Reactive Oxygen Species Mediated Apoptosis in Human Oral Squamous Carcinoma Cells

2021 ◽  
Vol 83 (5) ◽  
Author(s):  
Rajangam Pushpalatha ◽  
Ganapathy Sindhu ◽  
Ramalingam Sharmila ◽  
G. Tamizharasi ◽  
Lakshmanan Vennila ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Squamous Carcinoma ◽  
Carcinoma Cells ◽  
Oxygen Species ◽  
Squamous Carcinoma Cells ◽  
Oral Squamous Carcinoma

scholarly journals α-Lipoic Acid Induces Intrinsic Apoptosis in Human Oral Squamous Carcinoma Cells

2021 ◽  
Author(s):  
Revathi Duraisamy ◽  
Ezhilarasan Devaraj ◽  
Elumalai Perumal
Keyword(s):  
Gene Expression ◽  
Lipoic Acid ◽  
Squamous Carcinoma ◽  
Carcinoma Cells ◽  
Oxygen Species ◽  
Intrinsic Apoptosis ◽  
Apoptotic Gene ◽  
Squamous Carcinoma Cells ◽  
Oral Squamous Carcinoma ◽  
Dual Staining

Abstract Oral squamous cell carcinoma is one of the leading cancers in India and it is responsible for significant morbidity and mortality. α -lipoic acid, a co-factor for several metabolic enzymes, suppresses the tumor growth. In this study, we investigated the α-lipoic acid-induced cytotoxicity and apoptosis in human oral squamous carcinoma (SCC-25) cells. α-lipoic acid treatments were given to SCC-25 cells for 24 h and cell proliferation was evaluated by MTT assay. The reactive oxygen species expression was examined by dichloro-dihydro-fluorescein diacetate assay. Apoptosis-related morphological changes were detected by dual staining. Cytochrome c and RAS (H-Ras) expression was measured by dual staining and RT-PCR respectively. Intrinsic apoptosis-related markers are analyzed using qPCR.α-lipoic acid inhibited SCC-25 cell proliferation in a concentration-dependent manner. This treatment also increased intracellular reactive oxygen species expression and the percentage of apoptotic cells (up to 70% of the cell population). Dual staining further confirms cytochrome c cytosolic expression. The oncogene H-Ras protein and gene expression was also down-regulated upon α-lipoic acid treatment in SCC-25 cells. qPCR analysis further confirms α-lipoic acid-induced an upregulation of bax, Apaf-1, caspase 3 and − 9, pro-apoptotic gene expressions and downregulation of bcl-2, an anti-apoptotic gene expression. The present results suggest that α-lipoic acid has cytotoxic and pro-apoptotic potential and it also downregulates H-Ras oncogene expression in human oral squamous carcinoma cells. α-lipoic acid may have promising role in the treatment of human oral squamous carcinoma.

scholarly journals Intracellular Amplifiers of Reactive Oxygen Species Affecting Mitochondria as Radiosensitizers

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 208
Author(s):  
Hong-Gui Xu ◽  
Viktor Reshetnikov ◽  
Marit Wondrak ◽  
Lisa Eckhardt ◽  
Leoni A. Kunz-Schughart ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cancer Cells ◽  
Water Solubility ◽  
Reactive Oxygen ◽  
Squamous Carcinoma ◽  
Human Head ◽  
Oxygen Species ◽  
Squamous Carcinoma Cells ◽  
Close Proximity ◽  
Ic50 Values

Radiotherapy (RT) efficacy can be improved by using radiosensitizers, i.e., drugs enhancing the effect of ionizing radiation (IR). One of the side effects of RT includes damage of normal tissue in close proximity to the treated tumor. This problem can be solved by applying cancer specific radiosensitizers. N-Alkylaminoferrocene-based (NAAF) prodrugs produce reactive oxygen species (ROS) in cancer cells, but not in normal cells. Therefore, they can potentially act as cancer specific radiosensitizers. However, early NAAF prodrugs did not exhibit this property. Since functional mitochondria are important for RT resistance, we assumed that NAAF prodrugs affecting mitochondria in parallel with increasing intracellular ROS can potentially exhibit synergy with RT. We applied sequential Cu+-catalyzed alkyne-azide cycloadditions (CuAAC) to obtain a series of NAAF derivatives with the goal of improving anticancer efficacies over already existing compounds. One of the obtained prodrugs (2c) exhibited high anticancer activity with IC50 values in the range of 5–7.1 µM in human ovarian carcinoma, Burkitt’s lymphoma, pancreatic carcinoma and T-cell leukemia cells retained moderate water solubility and showed cancer specificity. 2c strongly affects mitochondria of cancer cells, leading to the amplification of mitochondrial and total ROS production and thus causing cell death via necrosis and apoptosis. We observed that 2c acts as a radiosensitizer in human head and neck squamous carcinoma cells. This is the first demonstration of a synergy between the radiotherapy and NAAF-based ROS amplifiers.

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