Deregulation of the CD44-NANOG-MDR1 associated chemoresistance pathways of breast cancer stem cells potentiates the anti-cancer effect of Kaempferol in synergism with Verapamil

Nandi, Sourav Kumar; Roychowdhury, Tanaya; Chattopadhyay, Samit; Basu, Sandip K.; Chatterjee, Krishti; Choudhury, Pritha; Banerjee, Nirmalya; Saha, Prosenjit; Mukhopadhyay, Soma; Mukhopadhyay, Ashis; Bhattacharya, R.K.

doi:10.1016/j.taap.2022.115887

Cited by 22 publications

(11 citation statements)

References 62 publications

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“…ABC transporters frequently overexpressed in BCSCs include multidrug-resistance-associated protein 1 (ABCC1, MRP1) and ATP-binding cassette superfamily G member 2 (ABCG2), also known as breast cancer resistance protein (BCRP) ( Koh et al, 2019 ; Sridharan et al, 2019 ). Another molecule of the ATP-dependent proton pump family essential for the resistance of cancer cells is P-glycoprotein (P-gp), the product of MDR1 (ABCB1) gene ( Nandi et al, 2022a ).…”

Section: Breast Cancer Stem Cells (Bcscs)mentioning

confidence: 99%

“…CSCs are also defined by aberrant expression or overactivation of specific molecules (such as transcription factors NANOG, SOX2, OCT4) that promote stemness and therapeutic resistance ( Nandi et al, 2022a ). Transcription factor SOX2 is crucial for embryonic development; however, SOX2 tends to be overexpressed in CSCs and to contribute to therapeutic resistance ( Novak et al, 2020 ).…”

Section: Breast Cancer Stem Cells (Bcscs)mentioning

confidence: 99%

“…NANOG regulates SOX2 to maintain the pluripotency of breast cancer cells. Moreover, the upregulation of SOX2 and OCT4 induced by NANOG depends on upregulated CD44-MDR1 network ( Nandi et al, 2022a ). The binding of hyaluronic acid to CD44 induces the activation of NANOG and associated STAT-3-mediated MDR1 gene expression.…”

Section: Breast Cancer Stem Cells (Bcscs)mentioning

confidence: 99%

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Therapy-resistant breast cancer in focus: Clinically relevant mitigation by flavonoids targeting cancer stem cells

et al. 2023

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Significant limitations of the reactive medical approach in breast cancer management are clearly reflected by alarming statistics recorded worldwide. According to the WHO updates, breast malignancies become the leading cancer type. Further, the portion of premenopausal breast cancer cases is permanently increasing and demonstrates particularly aggressive patterns and poor outcomes exemplified by young patients with triple-negative breast cancer that lacks targeted therapy. Accumulating studies suggest the crucial role of stem cells in tumour biology, high metastatic activity, and therapy resistance of aggressive breast cancer. Therefore, targeting breast cancer stem cells is a promising treatment approach in secondary and tertiary breast cancer care. To this end, naturally occurring substances demonstrate high potential to target cancer stem cells which, however, require in-depth analysis to identify effective anti-cancer agents for cost-effective breast cancer management. The current article highlights the properties of flavonoids particularly relevant for targeting breast cancer stem cells to mitigate therapy resistance. The proposed approach is conformed with the principles of 3P medicine by applying predictive diagnostics, patient stratification and treatments tailored to the individualised patient profile. Expected impacts are very high, namely, to overcome limitations of reactive medical services improving individual outcomes and the healthcare economy in breast cancer management. Relevant clinical applications are exemplified in the paper.

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Section: Breast Cancer Stem Cells (Bcscs)mentioning

confidence: 99%

Section: Breast Cancer Stem Cells (Bcscs)mentioning

confidence: 99%

Section: Breast Cancer Stem Cells (Bcscs)mentioning

confidence: 99%

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Therapy-resistant breast cancer in focus: Clinically relevant mitigation by flavonoids targeting cancer stem cells

et al. 2023

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“…According to a recent study, NANOG, SOX2, MDR1, and CD44 are all induced pluripotent stem cell markers that may be reduced by kaempferol alone or in conjunction with Verapamil. Cancer cells’ survival and acquisition may be slowed by pharmaceutical combinations that interfere with the CD44–NANOG–MDR1 feedback loop activation network, according to a new study [ 135 ]. The kaempferol could be effectively conjugated to the AuNCs.…”

Section: Anti-cancer Activities Of Kaempferol In Literature Cancer Typesmentioning

confidence: 99%

A systematic review of anti-cancer roles and mechanisms of kaempferol as a natural compound

2022

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It has been shown in multiple experimental and biological investigations that kaempferol, an edible flavonoid generated from plants, may be used as an anti-cancer drug and has been shown to have anti-cancer properties. Many signaling pathways are altered in cancer cells, resulting in cell growth inhibition and death in various tumor types. Cancer is a multifaceted illness coordinated by multiple external and internal mechanisms. Natural extracts with the fewest side effects have piqued the attention of researchers in recent years, attempting to create cancer medicines based on them. An extensive array of natural product-derived anti-cancer agents have been examined to find a successful method. Numerous fruits and vegetables have high levels of naturally occurring flavonoid kaempferol, and its pharmacological and biological effects have been studied extensively. Certain forms of cancer are sensitive to kaempferol-mediated anti-cancer activity, although complete research is needed. We have endeavored to concentrate our review on controlling carcinogenic pathways by kaempferol in different malignancies. Aside from its extraordinary ability to modify cell processes, we have also discussed how kaempferol has the potential to be an effective therapy for numerous tumors.

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“…Without the aim of high throughput results of omics platforms, Takahashi et al defined that “Yamanaka 4 factors”, including Oct3/4, Sox2, c-Myc, and Klf4, were the essential transcription factors required for reprogramming differentiated mouse fibroblasts, from both adult and embryonic, into pluripotent stem cells [ 36 ]. Thereafter, Yamanaka 4 factors became the paradigm of in vitro and in vivo pluripotency studies, and these four molecules have also been studied in the field of cancer stemness [ 7 , 37 , 38 , 39 , 40 , 41 ]. Besides iPSC, stimulus-triggered acquisition of pluripotency (STAP) was another approach that attempted to experimentally manipulate pluripotency.…”

Section: The History Of Stem Cell Investigation and Evidence Of The E...mentioning

confidence: 99%

Potential to Eradicate Cancer Stemness by Targeting Cell Surface GRP78

Chen

Cheng

2022

Biomolecules

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Cancer stemness is proposed to be the main cause of metastasis and tumor relapse after conventional therapy due to the main properties of cancer stem cells. These include unlimited self-renewal, the low percentage in a cell population, asymmetric/symmetric cell division, and the hypothetical different nature for absorbing external substances. As the mechanism of how cancer stemness is maintained remains unknown, further investigation into the basic features of cancer stemness is required. Many articles demonstrated that glucose-regulated protein 78 (GRP78) plays a key role in cancer stemness, suggesting that this molecule is feasible for targeting cancer stem cells. This review summarizes the history of finding cancer stem cells, as well as the functions of GRP78 in cancer stemness, for discussing the possibility of targeting GRP78 to eradicate cancer stemness.

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Deregulation of the CD44-NANOG-MDR1 associated chemoresistance pathways of breast cancer stem cells potentiates the anti-cancer effect of Kaempferol in synergism with Verapamil

Cited by 22 publications

References 62 publications

Therapy-resistant breast cancer in focus: Clinically relevant mitigation by flavonoids targeting cancer stem cells

Therapy-resistant breast cancer in focus: Clinically relevant mitigation by flavonoids targeting cancer stem cells

A systematic review of anti-cancer roles and mechanisms of kaempferol as a natural compound

Potential to Eradicate Cancer Stemness by Targeting Cell Surface GRP78

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