Tannic Acid Induces Endoplasmic Reticulum Stress-Mediated Apoptosis in Prostate Cancer

Endoplasmic reticulum (ER) stress is an intriguing target with significant clinical importance in chemotherapy. Interference with ER functions can lead to the accumulation of unfolded proteins, as detected by transmembrane sensors that instigate the unfolded protein response (UPR). Therefore, contro...

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Bibliographic Details
Published in:Cancers 2018-03, Vol.10 (3), p.68
Main Authors: Nagesh, Prashanth K B, Hatami, Elham, Chowdhury, Pallabita, Kashyap, Vivek K, Khan, Sheema, Hafeez, Bilal B, Chauhan, Subhash C, Jaggi, Meena, Yallapu, Murali M
Format: Article
Language:English
Subjects:
Acids
Apoptosis
Bcl-2 protein
Bcl-x protein
BIM protein
Caspase
Caspase-3
Chemotherapy
Cyclin D1
Cyclin-dependent kinase inhibitor p21
E-cadherin
Endoplasmic reticulum
Gelatinase A
Gelatinase B
Inositol
Invasiveness
Kinases
Metastases
Poly(ADP-ribose) polymerase
Prostate cancer
Protein folding
Protein kinase R
Proteins
Regulatory proteins
Tannic acid
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Summary:Endoplasmic reticulum (ER) stress is an intriguing target with significant clinical importance in chemotherapy. Interference with ER functions can lead to the accumulation of unfolded proteins, as detected by transmembrane sensors that instigate the unfolded protein response (UPR). Therefore, controlling induced UPR via ER stress with natural compounds could be a novel therapeutic strategy for the management of prostate cancer. Tannic acid (a naturally occurring polyphenol) was used to examine the ER stress mediated UPR pathway in prostate cancer cells. Tannic acid treatment inhibited the growth, clonogenic, invasive, and migratory potential of prostate cancer cells. Tannic acid demonstrated activation of ER stress response (Protein kinase R-like endoplasmic reticulum kinase (PERK) and inositol requiring enzyme 1 (IRE1)) and altered its regulatory proteins (ATF4, Bip, and PDI) expression. Tannic acid treatment affirmed upregulation of apoptosis-associated markers (Bak, Bim, cleaved caspase 3, and cleaved PARP), while downregulation of pro-survival proteins (Bcl-2 and Bcl-xL). Tannic acid exhibited elevated G₁ population, due to increase in p18 and p21 expression, while cyclin D1 expression was inhibited. Reduction of MMP2 and MMP9, and reinstated E-cadherin signifies the anti-metastatic potential of this compound. Altogether, these results demonstrate that tannic acid can promote apoptosis via the ER stress mediated UPR pathway, indicating a potential candidate for cancer treatment.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers10030068