Prostate apoptosis response-4 and tumor suppression: it’s not just about apoptosis anymore

Cheratta, Anees Rahman; Thayyullathil, Faisal; Pallichankandy, Siraj; Karthikeyan, S.; Alakkal, Ameer; Galadari, Sehamuddin

doi:10.1038/s41419-020-03292-1

Cited by 18 publications

(15 citation statements)

References 135 publications

(204 reference statements)

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“…UACA is an oncogene known to induce apoptosis resistance in cancer ( 117 ). UACA expression is regulated by p53 activation and/or inhibition of NF-κB activity ( 118 ). Coincidently, ST08 upregulated p53 and downregulated NF-κB.…”

Section: Discussionmentioning

confidence: 99%

ST08 Altered NF-κB Pathway in Breast Cancer Cells In Vitro as Revealed by miRNA-mRNA Analysis and Enhanced the Effect of Cisplatin on Tumour Reduction in EAC Mouse Model

et al. 2022

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ST08 is a novel curcumin derivative that exhibited apoptotic and anti-migratory activity in MDA-MB-231, triple-negative breast cancer cells reported earlier. In this study, we further explored the anticancer properties of ST08. ST08 reduced tumor burden in vivo and induced apoptosis through the mitochondrial pathway both in vitro and in vivo. ST08 potentiated the effect of cisplatin in vitro and in vivo in mouse EAC breast cancer models with minimal toxicity. ST08 induced alterations in the gene expression were studied by parallel analysis of miRNA and mRNA. 74 differentially expressed miRNA regulated 114 mRNA in triple-negative (MDA-MB-231) cancer cells. Pathway related to the ECM was altered in mesenchymal MDA-MB-231 cells. We constructed a unique miRNA-mRNA interaction network, and one of the pathways regulated by miRNA was NF-κB. Targets of NF-κB like MMP1, PTX3, and MMP2 were downregulated in MDA-MB-231 in response to ST08 treatment. PMA induced cell proliferation was abrogated by ST08 treatment, and no additional cell cytotoxicity was observed when used in combination with IKK-16 indicating ST08 regulation of NF-κB pathway in MDA-MB-231 cells.

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Section: Discussionmentioning

confidence: 99%

ST08 Altered NF-κB Pathway in Breast Cancer Cells In Vitro as Revealed by miRNA-mRNA Analysis and Enhanced the Effect of Cisplatin on Tumour Reduction in EAC Mouse Model

et al. 2022

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“…One of the important features of any potential anti-cancer agent is to differentially modulate the expression of tumor suppressors and/or oncogenes. Par-4, a tumor suppressor protein, can selectively cause apoptosis in a wide variety of cancers without affecting normal cells [46]. However, Par-4 is known to be down-regulated in several cancers [46].…”

Section: Discussionmentioning

confidence: 99%

“…Par-4, a tumor suppressor protein, can selectively cause apoptosis in a wide variety of cancers without affecting normal cells [46]. However, Par-4 is known to be down-regulated in several cancers [46]. Therefore, agents that can induce Par-4 from either normal and/or cancer cells are an attractive therapeutic option.…”

Section: Discussionmentioning

confidence: 99%

Prostate Apoptosis Response-4 (Par-4): A Novel Target in Pyronaridine-Induced Apoptosis in Glioblastoma (GBM) Cells

Ghosalkar

Sonawane

Pisal

et al. 2022

Cancers

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Glioblastoma (GBM) is an aggressive form of brain tumor with a median survival of approximately 12 months. With no new drugs in the last few decades and limited success in clinics for known therapies, drug repurposing is an attractive choice for its treatment. Here, we examined the efficacy of pyronaridine (PYR), an anti-malarial drug in GBM cells. PYR induced anti-proliferative activity in GBM cells with IC50 ranging from 1.16 to 6.82 µM. Synergistic activity was observed when PYR was combined with Doxorubicin and Ritonavir. Mechanistically, PYR triggered mitochondrial membrane depolarization and enhanced the ROS levels causing caspase-3 mediated apoptosis. PYR significantly decreased markers associated with proliferation, EMT, hypoxia, and stemness and upregulated the expression of E-cadherin. Interestingly, PYR induced the expression of intracellular as well as secretory Par-4, a tumor suppressor in GBM cells, which was confirmed using siRNA. Notably, Par-4 levels in plasma samples of GBM patients were significantly lower than normal healthy volunteers. Thus, our study demonstrates for the first time that PYR can be repurposed against GBM with a novel mechanism of action involving Par-4. Herewith, we discuss the role of upregulated Par-4 in a highly interconnected signaling network thereby advocating its importance as a therapeutic target.

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“…Nevertheless, cannabinoid receptors have been shown to control other various signaling pathways that are directly involved in the regulation of cell proliferation and cell death. These signals include the extracellular-signal-regulated-kinase (ERK) as one of the major signaling pathways of the mitogen-activated protein kinase (MAPK) [62], and p38 MAPK [63], phosphatidylinositol 3-kinase (PI3K)/Akt [64], focal adhesion kinase [65], and ceramide and reactive oxygen species (ROS) pathways in prostate cancer [66].…”

Section: Cell Signaling Mediated By Cannabinoid Receptorsmentioning

confidence: 99%

The Pathophysiology and the Therapeutic Potential of Cannabinoids in Prostate Cancer

Singh

Nassar

Bachari

et al. 2021

Cancers

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Prostate cancer is the second most frequently occurring cancer diagnosed among males. Recent preclinical evidence implicates cannabinoids as powerful regulators of cell growth and differentiation. In this review, we focused on studies that demonstrated anticancer effects of cannabinoids and their possible mechanisms of action in prostate cancer. Besides the palliative effects of cannabinoids, research from the past two decades has demonstrated their promising potential as antitumor agents in a wide variety of cancers. This analysis may provide pharmacological insights into the selection of specific cannabinoids for the development of antitumor drugs for the treatment of prostate cancer.

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Prostate apoptosis response-4 and tumor suppression: it’s not just about apoptosis anymore

Cited by 18 publications

References 135 publications

ST08 Altered NF-κB Pathway in Breast Cancer Cells In Vitro as Revealed by miRNA-mRNA Analysis and Enhanced the Effect of Cisplatin on Tumour Reduction in EAC Mouse Model

ST08 Altered NF-κB Pathway in Breast Cancer Cells In Vitro as Revealed by miRNA-mRNA Analysis and Enhanced the Effect of Cisplatin on Tumour Reduction in EAC Mouse Model

Prostate Apoptosis Response-4 (Par-4): A Novel Target in Pyronaridine-Induced Apoptosis in Glioblastoma (GBM) Cells

The Pathophysiology and the Therapeutic Potential of Cannabinoids in Prostate Cancer

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