scholarly journals 2-Methoxyestradiol and Its Combination with a Natural Compound, Ferulic Acid, Induces Melanoma Cell Death via Downregulation of Hsp60 and Hsp90

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Anna Kamm ◽  
Paulina Przychodzeń ◽  
Alicja Kuban–Jankowska ◽  
Antonella Marino Gammazza ◽  
Francesco Cappello ◽  
...  
Keyword(s):  
Cell Death ◽  
Ferulic Acid ◽  
Melanoma Cell ◽  
Cell Model ◽  
Clinical Importance ◽  
Hsp70 Expression ◽  
Cellular Model ◽  
Anticancer Efficacy ◽  
Cancer Cell Death ◽  
A375 Melanoma

Melanoma is an aggressive type of skin cancer with one of the highest mortality rates. Notably, its incidence in the last few decades has increased faster than any other cancer. Therefore, searching for novel anticancer therapies is of great clinical importance. In the present study, we investigated the anticancer potential of 2-methoxyestradiol, potent chemotherapeutic, in the A375 melanoma cellular model. In order to furthermore evaluate the anticancer efficacy of 2-methoxyestradiol, we have additionally combined the treatment with a naturally occurring polyphenol, ferulic acid. The results were obtained using the melanoma A375 cellular model. In the study, we used MTT assay, flow cytometry, and western blot techniques. Herein, we have evidenced that the molecular mechanism of action of 2-methoxyestradiol and ferulic acid is partly related to the reduction of Hsp60 and Hsp90 levels and the induction of nitric oxide in the A375 melanoma cell model, while no changes were observed in Hsp70 expression after 2-methoxyestradiol and ferulic acid treatment separately or in combination. This is especially important in case of chemoresistance mechanisms because the accumulation of Hsp70 reduces induction of cancer cell death, thus decreasing antitumour efficacy.

scholarly journals Diclofenac Potentiates Sorafenib-Based Treatments of Hepatocellular Carcinoma by Enhancing Oxidative Stress

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1453 ◽  
Author(s):  
Duval ◽  
Troquier ◽  
de Souza Silva ◽  
Demartines ◽  
Dormond
Keyword(s):  
Oxidative Stress ◽  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Hepatocellular Cancer ◽  
Tumor Burden ◽  
Anticancer Efficacy ◽  
Cancer Cell Death ◽  
Liver Cancers ◽  
Valuable Treatment ◽  
Anti Oxidant

Sorafenib is the first developed systemic treatment for advanced forms of hepatocellular carcinoma, which constitutes the most frequent form of primary liver cancers and is a major global health burden. Although statistically significant, the positive effect of sorafenib on median survival remains modest, highlighting the need to develop novel therapeutic approaches. In this report, we introduce diclofenac, a nonsteroidal anti-inflammatory drug, as a potent catalyzer of sorafenib anticancer efficacy. Treatment of three different hepatocellular cancer cells (Huh-7, HepG2, and PLC-PRF-5) with sorafenib (5 µM, 24 h) and diclofenac (100 µM, 24 h) significantly increased cancer cell death compared to sorafenib or diclofenac alone. Anti-oxidant compounds, including N-acetyl-cysteine and ascorbic acid, reversed the deleterious effects of diclofenac/sorafenib co-therapy, suggesting that the generation of toxic levels of oxidative stress was responsible for cell death. Accordingly, whereas diclofenac increased production of mitochondrial oxygen reactive species, sorafenib decreased concentrations of glutathione. We further show that tumor burden was significantly diminished in mice bearing tumor xenografts following sorafenib/diclofenac co-therapy when compared to sorafenib or diclofenac alone. Taken together, these results highlight the anticancer benefits of sorafenib/diclofenac co-therapy in hepatocellular carcinoma. They further indicate that combining sorafenib with compounds that increase oxidative stress represents a valuable treatment strategy in hepatocellular carcinoma.

Cancer cell death

2016 ◽  
pp. 42-48
Author(s):  
Amanda S. Coutts ◽  
Sandra Maniam ◽  
Nicholas B. La Thangue
Keyword(s):  
Cell Death ◽  
Cancer Cell ◽  
Control Cell ◽  
Clinical Importance ◽  
Signalling Pathways ◽  
Cancer Treatments ◽  
Cell Death Pathways ◽  
Cancer Cell Death ◽  
Cell Death Mechanisms ◽  
Apoptotic Pathways

Inducing cancer cell death is the basis of the majority of cancer treatments and understanding the mechanisms that control cell death is of prime clinical importance. As a defining feature of cancer is the ability to circumvent cell death pathways, understanding the mechanisms involved is also important in the development of novel therapeutic agents. This chapter outlines three main mechanisms involved in cancer cell death—apoptosis, necroptosis, and autophagy—to give an overview of some of the specific pathways involved. There are a plethora of genetic and epigenetic changes in tumour cells that can circumvent apoptotic pathways; as such understanding and developing therapies that can target other death-signalling pathways could have great clinical significance. Given the complexity involved in the variety of cell death mechanisms, the challenge in oncology is how to harness these different modes of cell death in order to effectively eliminate cancer cells.

New Insight into 2-Methoxyestradiol- a Possible Physiological Link between Neurodegeneration and Cancer Cell Death

2016 ◽  
Vol 23 (15) ◽  
pp. 1513-1527 ◽  
Author(s):  
Magdalena Gorska ◽  
Alicja Kuban-Jankowska ◽  
Jaroslaw Slawek ◽  
Michal Wozniak
Keyword(s):  
Cell Death ◽  
Cancer Cell ◽  
Cancer Cell Death ◽  
Insight Into

Zinc chelator TPEN induces pancreatic cancer cell death through causing oxidative stress and inhibiting cell autophagy

2019 ◽  
Vol 234 (11) ◽  
pp. 20648-20661 ◽  
Author(s):  
Zhen Yu ◽  
Ze Yu ◽  
ZhenBao Chen ◽  
Lin Yang ◽  
MingJun Ma ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pancreatic Cancer ◽  
Cell Death ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Death ◽  
Zinc Chelator

Magneto Mitochondrial Dysfunction Mediated Cancer Cell Death Using Intracellular Magnetic Nano-Transducers

2021 ◽  
Author(s):  
Wooram Park ◽  
Seok-Jo Kim ◽  
Paul Cheresh ◽  
Jeanho Yun ◽  
Byeongdu Lee ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Therapy ◽  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Cancer Cell ◽  
High Sensitivity ◽  
Intrinsic Pathway ◽  
Cancer Cell Death

Mitochondria are crucial regulators of the intrinsic pathway of cancer cell death. The high sensitivity of cancer cells to mitochondrial dysfunction offers opportunities for emerging targets in cancer therapy. Herein,...

scholarly journals Correction to Inducing Cancer Cell Death by Targeting Its Nucleus: Solid Gold Nanospheres versus Hollow Gold Nanocages

2013 ◽  
Vol 24 (8) ◽  
pp. 1414-1414 ◽  
Author(s):  
Megan A. Mackey ◽  
Farhat Saira ◽  
Mahmoud A. Mahmoud ◽  
Mostafa A. El-Sayed
Keyword(s):  
Cell Death ◽  
Cancer Cell ◽  
Gold Nanospheres ◽  
Solid Gold ◽  
Cancer Cell Death ◽  
Gold Nanocages
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