Bishonokiol A Induces Multiple Cell Death in Human Breast Cancer MCF-7 Cells

Li, Hongmei; Li, Bohan; Ma, Hui; Sun, Xiaolong; Zhu, Meilin; Dai, Yiqun; Ma, Tao; Huo, Qiang; Wu, Cheng‐Zhu

doi:10.31557/apjcp.2020.21.4.1073

Cited by 3 publications

(3 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although these combinations were observed to trigger necroptosis, many of them were found to involve mechanisms and pathways (RIPK‐1 independent, cathepsin mediated, ROS and PARP‐1 mediated) distinct from the conventional one (TNF‐α➔ RIPK‐1➔ RIPK‐3➔ MLKL) 4,6,7 . Only a few drugs (shikonin, ANT4, bishonikiol) and combinations [(3‐bromopyruvate + chloroquine + Z‐VAD‐FMK), (JG‐98 + 17 DMAG + Bortezomib + Etoposide + ZVAD‐FMK + SM164)] were reported to induce necroptosis via the canonical pathway 8–13 . The drug shikonin was found to be effective in inducing necroptosis in breast cancer cells by causing an upregulation of its key molecules.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Relative refractoriness of breast cancer cells to tumour necrosis factor‐α induced necroptosis

Thakur

Saha

Bhatia

2022

Clin Exp Pharma Physio

View full text Add to dashboard Cite

Necroptosis, a recently identified programmed cell death pathway, has attracted attention as an alternative route to target apoptosis-resistant cancer cells. The status of the necroptosis pathway in different subtypes of breast cancer has not been well explored. Stimulating the cells by TNF-α can trigger cell survival or death depending on the combination of downstream players involved. In this work, we attempted to induce necroptosis in them using a combination of TNF-α and Z-VAD-FMK with and without chemotherapy. Cell viability, apoptosis, and necroptosis were assessed using MTT and Annexin-V/PI assays, respectively. Gene and protein expression was analysed by qPCR and immunophenotyping. Both the cell lines were resistant to induction of cell death by necroptosis. There was no enhancement in cell death when chemotherapeutic drugs were combined with necroptosis induction. Expression studies showed reduced translational expression of key necroptosis molecules like RIP kinases and MLKL in breast cancer cells compared to positive control cell line L929. Also, cell survival molecules were expressed more in MDA-MB-231 in contrast to death pathway molecules which were expressed more in T47D cells. In this work, the two breast cancer cell lines were observed to be resistant to TNF-α induced necroptosis with or without chemotherapy. Expression of key necroptosis players revealed relative insufficiency of the molecular machinery involved in the above pathway. In our opinion this may be the cause for resistance to necroptosis and novel strategies to upregulate these molecules need to be developed to sensitize the breast cancer cells towards cell death by necroptosis.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Etoposide + ZVAD-FMK + SM164)] were reported to induce necroptosis via the canonical pathway. [8][9][10][11][12][13] The drug shikonin was found to be effective in inducing necroptosis in breast cancer cells by causing an upregulation of its key molecules.…”

Section: Decreased Basal Expression Of Key Necroptosis Molecules In B...mentioning

confidence: 99%

Relative refractoriness of breast cancer cells to tumour necrosis factor‐α induced necroptosis

Thakur

Saha

Bhatia

2022

Clin Exp Pharma Physio

View full text Add to dashboard Cite

show abstract

“…Indeed, CypD-ANT1 association was also involved in the therapeutic mechanisms of several other antitumor drugs (72)(73)(74). Furthermore, both bishonokiol A and 1, 2-Diarachidonoyl-Sn-glycero-3-phosphoethanolamine (DAPE) upregulated CypD expression by activating the RIP1/RIP3/ MLKL necrosis cascade, thus promoting mPTP-mediated necrosis of breast cancer and malignant pleural mesothelioma cells (75,76). Similarly, bromocriptine could also promote the phosphorylation of CypD through the RIP3/MLKL pathway, thus inducing necrosis of prolactinoma cells (77).…”

Section: Promotion Of Tumor Cell Deathmentioning

confidence: 99%

Cyclophilin D: Guardian or Executioner for Tumor Cells?

et al. 2022

View full text Add to dashboard Cite

Cyclophilin D (CypD) is a peptide-proline cis-trans isomerase (PPIase) distributed in the mitochondrial matrix. CypD regulates the opening of the mitochondrial permeability conversion pore (mPTP) and mitochondrial bioenergetics through PPIase activity or interaction with multiple binding partners in mitochondria. CypD initially attracted attention due to its regulation of mPTP overopening-mediated cell death. However, recent studies on the effects of CypD on tumors have shown conflicting results. Although CypD has been proven to promote the aerobic glycolysis in tumor cells, its regulation of malignant characteristics such as the survival, invasion and drug resistance of tumor cells remains controversial. Here, we elaborate the main biological functions of CypD and its relationships with tumor progression identified in recent years, focusing on the dual role of CypD in tumors.

show abstract

Effect of aspirin on the TNF-α-mediated cell survival and death pathways in breast cancer

Thakur

Saha

Dahiya

et al. 2022

Journal of Basic and Clinical Physiology and Pharmacology

View full text Add to dashboard Cite

Objectives Aspirin is an anti-inflammatory drug commonly used as an analgesic and in cardiovascular disorders. However, many studies have highlighted its anti-cancer properties, especially in colorectal, lung, head and neck, and breast cancers. In this work, we tried to study the effect of aspirin on the TNF-α-mediated cell survival and death pathways in two cell lines representing two different subtypes of breast cancer. TNF-α-mediated stimulation of a cell can result in its proliferation via the NF-κB pathway or its death via either apoptosis or a programmed form of necrosis called necroptosis. The latter is believed to come into the picture only when apoptosis is inhibited. Methods In this work, we studied the effect of aspirin on the TNF-α-mediated cell survival pathway and observed a decrease in expression of the NF-κB pathway regulators, its nuclear translocation, and phosphorylation in a dose-dependent manner. The effect of aspirin on the TNF-α-mediated cell death showed significant cytotoxicity at the higher doses (5–20 mM) of aspirin in both the breast cancer cell lines. The effect of aspirin on necroptosis was investigated after stimulating the cells with TNF-α and inhibiting apoptosis using Z-VAD-FMK. Results Though no significant effect was noted in breast cancer cell lines, the above protocol successfully induced necroptosis in L929, i.e., a positive control cell line for necroptosis having an intact necroptosis machinery. Even when combined with the chemotherapeutic drugs, the above regime failed to induce any significant necroptosis in breast cancer cells but was found effective in L929. Conclusions Overall, the findings show that while aspirin has the potential to inhibit the TNF-α-mediated cell survival pathway, it does not help sensitize breast cancer cells to necroptotic cell death induction.

show abstract

Bishonokiol A Induces Multiple Cell Death in Human Breast Cancer MCF-7 Cells

Cited by 3 publications

References 27 publications

Relative refractoriness of breast cancer cells to tumour necrosis factor‐α induced necroptosis

Relative refractoriness of breast cancer cells to tumour necrosis factor‐α induced necroptosis

Cyclophilin D: Guardian or Executioner for Tumor Cells?

Effect of aspirin on the TNF-α-mediated cell survival and death pathways in breast cancer

Contact Info

Product

Resources

About