[10]-Gingerol Reverts Malignant Phenotype of Breast Cancer Cells in 3D Culture

Fuzer, Angelina Maria; Lee, Sun-Young; Mott, Joni D.; Cominetti, Márcia Regina

doi:10.1002/jcb.25906

Cited by 24 publications

(9 citation statements)

References 31 publications

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“…Most important is the diversity within the tumor microenvironment (TM) in terms of the stromal cells present, the amount of oxygen available and the acidity of the environment [ 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. Another important difference is the amount of the extracellular matrix (ECM) proteins around the cancer cells [ 25 , 26 , 27 ]. ECM proteins can create a barrier through which the drugs must pass in order to reach the cancer cells while their presence promote tumor metastasis [ 28 , 29 , 30 , 31 , 32 , 33 , 34 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of Tumor Microenvironment in Chemoresistance: To Survive, Keep Your Enemies Closer

Senthebane

Rowe

Thomford

et al. 2017

IJMS

334

330

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Chemoresistance is a leading cause of morbidity and mortality in cancer and it continues to be a challenge in cancer treatment. Chemoresistance is influenced by genetic and epigenetic alterations which affect drug uptake, metabolism and export of drugs at the cellular levels. While most research has focused on tumor cell autonomous mechanisms of chemoresistance, the tumor microenvironment has emerged as a key player in the development of chemoresistance and in malignant progression, thereby influencing the development of novel therapies in clinical oncology. It is not surprising that the study of the tumor microenvironment is now considered to be as important as the study of tumor cells. Recent advances in technological and analytical methods, especially ‘omics’ technologies, has made it possible to identify specific targets in tumor cells and within the tumor microenvironment to eradicate cancer. Tumors need constant support from previously ‘unsupportive’ microenvironments. Novel therapeutic strategies that inhibit such microenvironmental support to tumor cells would reduce chemoresistance and tumor relapse. Such strategies can target stromal cells, proteins released by stromal cells and non-cellular components such as the extracellular matrix (ECM) within the tumor microenvironment. Novel in vitro tumor biology models that recapitulate the in vivo tumor microenvironment such as multicellular tumor spheroids, biomimetic scaffolds and tumor organoids are being developed and are increasing our understanding of cancer cell-microenvironment interactions. This review offers an analysis of recent developments on the role of the tumor microenvironment in the development of chemoresistance and the strategies to overcome microenvironment-mediated chemoresistance. We propose a systematic analysis of the relationship between tumor cells and their respective tumor microenvironments and our data show that, to survive, cancer cells interact closely with tumor microenvironment components such as mesenchymal stem cells and the extracellular matrix.

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Section: Introductionmentioning

confidence: 99%

The Role of Tumor Microenvironment in Chemoresistance: To Survive, Keep Your Enemies Closer

Senthebane

Rowe

Thomford

et al. 2017

IJMS

334

330

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“…Our study showed that [10]-gingerol is a more potent inhibitor than [6]- or [8]-gingerol, with selectivity towards breast cancer cells compared to normal fibroblasts in vitro . In addition, more recently we have demonstrated that [10]-gingerol is able to revert the malignant phenotype of breast cancer cells in three-dimensional culture [ 20 ]. Interestingly, [10]-gingerol also mediates potent anti-neuroinflammatory activity [ 21 ], an important manifestation likely to contribute to the development of brain metastases [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

[10]-gingerol induces apoptosis and inhibits metastatic dissemination of triple negative breast cancer in vivo

et al. 2017

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There is increasing interest in the use of non-toxic natural products for the treatment of various pathologies, including cancer. In particular, biologically active constituents of the ginger oleoresin (Zingiber officinale Roscoe) have been shown to mediate anti-tumour activity and to contribute to the anti-inflammatory, antioxidant, antimicrobial, and antiemetic properties of ginger. Here we report on the inhibitory properties of [10]-gingerol against metastatic triple negative breast cancer (TNBC) in vitro and in vivo. We show that [10]-gingerol concentration-dependently induces apoptotic death in mouse and human TNBC cell lines in vitro. In addition, [10]-gingerol is well tolerated in vivo, induces a marked increase in caspase-3 activation and inhibits orthotopic tumour growth in a syngeneic mouse model of spontaneous breast cancer metastasis. Importantly, using both spontaneous and experimental metastasis assays, we show for the first time that [10]-gingerol significantly inhibits metastasis to multiple organs including lung, bone and brain. Remarkably, inhibition of brain metastasis was observed even when treatment was initiated after surgical removal of the primary tumour. Taken together, these results indicate that [10]-gingerol may be a safe and useful complementary therapy for the treatment of metastatic breast cancer and warrant further investigation of its efficacy, either alone or in combination with standard systemic therapies, in pre-clinical models of metastatic breast cancer and in patients.

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“…10-gingerol has been previously reported to exert anti-tumor activity in TNBC, by inhibiting tumor cells proliferation, invasion, and metastasis, as well as by inducing apoptosis, both in vitro and in vivo 20,28,29 . Additionally, 10-gingerol demonstrated potent anti-tumor effects on non-TNBCs and other types of cancer 30,31 . To the best of our knowledge, 8-gingerol has not been previously reported to have anti-tumor activity in TNBC; thus, herein, we provide for the first-time evidence that suggests the potential use of 8-gingerol in TNBC treatment.…”

Section: Discussionmentioning

confidence: 99%

Efficacy based ginger fingerprinting reveals potential antiproliferative analytes for triple negative breast cancer

Zhao

Rupji

Choudhary

et al. 2020

Sci Rep

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Ginger (Zingiber officinale) is one of the most widely consumed dietary supplements worldwide. Its anticancer potential has been demonstrated in various studies. However, ginger roots obtained from different geographical locations showed extensive variability in their activities, mainly due to differences in the levels of bioactive compounds. Here we evaluated the effect of these differences on the anticancer activity of ginger by performing efficacy-based fingerprinting. We characterized the fingerprint profiles of 22 ginger samples using liquid chromatography-mass spectroscopy, followed by a principal component analysis (PCA) and pearson correlation analysis. We also evaluated the anti-proliferative effects (IC50) of these samples on triple-negative breast cancer cells using the MTT assays. The supervised PCA identified a subset of analytes whose abundance strongly associated with the IC50 values of the ginger extracts, providing a link between ginger extract composition and in vitro anticancer efficacy. This study demonstrated that variation in the ginger fingerprint profiles resulting from differences in their chemical composition could have a significant impact on efficacy and bioactivity of ginger extracts. Also, this first-of-a-kind efficacy-based fingerprinting approach proposed here can identify potent anticancer candidates from the ginger fingerprint without the need for isolating individual components from the extracts.

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[10]-Gingerol Reverts Malignant Phenotype of Breast Cancer Cells in 3D Culture

Cited by 24 publications

References 31 publications

The Role of Tumor Microenvironment in Chemoresistance: To Survive, Keep Your Enemies Closer

The Role of Tumor Microenvironment in Chemoresistance: To Survive, Keep Your Enemies Closer

[10]-gingerol induces apoptosis and inhibits metastatic dissemination of triple negative breast cancer in vivo

Efficacy based ginger fingerprinting reveals potential antiproliferative analytes for triple negative breast cancer

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