SERCA and P-glycoprotein inhibition and ATP depletion are necessary for celastrol-induced autophagic cell death and collateral sensitivity in multidrug-resistant tumor cells

Cancer is characterized by the often rapid and uncontrolled rate of cell growth. This alteration in growth pattern causes normal cells to become tumor cells. After undergoing a period of chemotherapy, some tumor cells become resistant to a variety of drugs, a phenomenon known as the multidrug resistance (MDR). One explanation for this change is the overexpression of P-glycoprotein in the drug-resistant cells. This membrane protein is capable of pumping drugs into the extracellular medium. Since the drugs do not accumulate, the tumor cells are not killed. In order to examine this protein, a contact mode AFM was used to image the cell membranes of both the normal and the MDR tumor cells. The four figures provided show the topographical information of the membranes and suggest that there are differences between the cell lines.

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A model for computer simulation of P-glycoprotein and transmembrane ΔpH-mediated anthracycline transport in multidrug-resistant tumor cells

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research ◽

10.1016/0167-4889(90)90111-p ◽

1990 ◽

Vol 1055 (2) ◽

pp. 117-125 ◽

Cited By ~ 41

Author(s):

Erland J.F. Demant ◽

Maxwell Sehested ◽

Peter Buhl Jensen

Keyword(s):

Computer Simulation ◽

Tumor Cells ◽

Multidrug Resistant ◽

P Glycoprotein

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New Insight into Triple-Negative Breast Cancer Therapy: The Potential Roles of Endoplasmic Reticulum Stress and Autophagy Mechanisms

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200619180716 ◽

2020 ◽

Vol 20 ◽

Author(s):

Milad Ashrafizadeh ◽

Reza Mohammadinejad ◽

Shima Tavakol ◽

Zahra Ahmadi ◽

Amihossein Sahebkar

Keyword(s):

Breast Cancer ◽

Endoplasmic Reticulum ◽

Cell Death ◽

Er Stress ◽

Tumor Cells ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Breast Cancer Mortality ◽

Autophagic Cell Death ◽

Cancer Pathology

Background: Breast cancer is accounted as the fifth leading cause of mortality among the other cancers. Notwithstanding, Triple Negative Breast Cancer (TNBC) is responsible for the 15-20% of breast cancer mortality. Despite the many investigations, it remains incurable in part due to insufficient understanding of its exact mechanisms. Methods: A literature search was performed in PubMed, SCOPUS and Web of Science databases using the keywords autophagy, Endoplasmic Reticulum (ER) stress, apoptosis, TNBC and the combinations of these keywords. Results: It was found that autophagy plays a dual role in cancer, so that it may decrease the viability of tumor cells or act as a cytoprotective mechanism. It then appears that using compounds having modulatory effects on autophagy is of importance in terms of induction of autophagic cell death and diminishing the proliferation and metastasis of tumor cells. Also, ER stress can be modulated in order to stimulate apoptotic and autophagic cell death in tumor cells. Conclusion: Perturbation in the signaling pathways related to cell survival leads to the initiation and progression of cancer. Regarding the advancement in the cancer pathology, it seems that modulation of autophagy and ER stress are promising.

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