AKT inhibitor AZD5363 suppresses stemness and promotes anti-cancer activity of 3,3′-diindolylmethane in human breast cancer cells

Zhu, Kaiyuan; Liu, Xu; Liu, Chunxiao; Xu, Yuting; Fu, Yingqiang; Dong, Wei; Yan, Yadong; Wang, Wenjing; Qian, Cheng

doi:10.1016/j.taap.2021.115700

“…This technique allows for routine 40-plex experiments and theoretically enables 100-plex studies. Similar to scRNA-seq and flow cytometry, CyTOF has been used to study the immune tumor microenvironment (Norton et al, 2019;Zhang et al, 2019;Zhu et al, 2021). Zhu et al were able to use such data to link AKT activity to chemotherapy resistance in breast cancer cells and showed that AKT inhibition increased cell death (Zhu et al, 2021).…”

Section: Proteinsmentioning

confidence: 99%

“…Similar to scRNA-seq and flow cytometry, CyTOF has been used to study the immune tumor microenvironment ( Norton et al, 2019 ; Zhang et al, 2019 ; Zhu et al, 2021 ). Zhu et al were able to use such data to link AKT activity to chemotherapy resistance in breast cancer cells and showed that AKT inhibition increased cell death ( Zhu et al, 2021 ). CyTOF provides a unique profile of a tumor and has been used to develop a computational framework to identify the optimal combination therapy for a patient ( Anchang et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Achieving a Deeper Understanding of Drug Metabolism and Responses Using Single-Cell Technologies

Wheeler

¹

,

Eberhard

²

,

Mosher

³

et al. 2023

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Recent advancements in single-cell technologies have enabled detection of RNA, proteins, metabolites, and xenobiotics in individual cells, and the application of these technologies has the potential to transform pharmacological research. Single-cell data has already resulted in the development of human and model species cell atlases, identifying different cell-types within a tissue, further facilitating the characterization of tumor heterogeneity and providing insight into treatment resistance. Research discussed in this review demonstrates that distinct cell populations express drug metabolizing enzymes to different extents, indicating there may be variability in drug metabolism not only between organs, but within tissue types. Additionally, we put forth the concept that single-cell analyses can be utilized to expose underlying variability in cellular response to drugs, providing a unique examination of drug efficacy, toxicity, and metabolism.We will outline several of these techniques: single-cell RNA-sequencing and mass cytometry to characterize and distinguish different cell types, single-cell proteomics to quantify drug metabolizing enzymes and characterize cellular responses to drug, capillary electrophoresisultrasensitive laser-induced fluorescence detection and single-probe single-cell mass spectrometry for detection of drugs, and others. Emerging single-cell technologies such as these can comprehensively characterize heterogeneity in both cell-type specific drug metabolism and response to treatment, enhancing progress toward personalized and precision medicine.

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“…Such a study was done by Zhu et al, where they observed that the effect of AZD5363, an Akt inhibitor was successful in reducing stemness of the breast cancer cell line MCF-7. It was used in a combinatorial approach alongside 3,3'-diindoylmethane and it was also observed that the anti-cancer effect of the drug and induced DIM induced apoptosis in the cells 75 . Luminal A breast cancer cells are again a potential biomarker for modifying the phenotypic plasticity amongst the cells leading to aggressive and inducting resistance towards therapy.…”

Section: Potential Treatments Targeting Cell-intrinsic Pathways Media...mentioning

confidence: 99%

The Unholy Trinity- Cancer cell plasticity, drug resistance and therapeutic opportunities

Chatterjee

¹

,

Pulipaka

²

,

Subbalakshmi

³

et al. 2023

Preprint

0

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Cancer cell plasticity is the ability of tumor cells to switch phenotypes and is one of the predominant requisites of cancer cells capable of undergoing metastasis. Cancer cell plasticity is also recognised as one of the major contributors to intra-tumoral heterogeneity, a critical factor underlying the progression of malignant tumors which is known to modify tumor response and induce resistance against various modes of therapy thus posing a barrier to efficient cancer management. Cancer cell plasticity is acquired by the subversion of cell signaling pathways like MAPK, PI3K, STAT3, Wnt, Hedgehog and Notch as well as cellular programs such as epithelial to mesenchymal transition (EMT) and phenotypic plasticity. This complex phenomenon has been studied in many cancer types like pancreatic cancer, colon cancer and breast cancer. Some cancers like breast cancer are known to exhibit a hierarchical organization with cancer stem cells (CSCs) at the pinnacle of the pyramid due to their ability to promote tumorigenesis, metastasis and therapy resistance. CSCs which can undergo phenotypic changes resulting in heterogenous cell populations with differing potential to develop programs necessary for the metastatic process lies at the core of the cancer cell plasticity hypothesis. Our expanding knowledge of this field can lead to the development of more therapeutic strategies that can be used in cancer and other solid tumors that exhibit similar mechanisms of plasticity. This review will explore the current understanding we have of breast cancer on the intrinsic molecular mechanisms of cancer cell plasticity and the resistance to various types of cancer therapy that arise as a result of plasticity. We conclude by exploring the potential novel therapies that specifically target the pathways leading to plasticity and can be leveraged to treat patients living with the disease. Keywords: Cancer cell plasticity, Epithelial to Mesenchymal Transition (EMT), therapy resistance, targeted therapy.

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“…Zhu et al observed that AZD5363, an Akt inhibitor, was successful in reducing stemness in the breast cancer cell line MCF-7. It was used in combination with 3,3′-diindoylmethane to induce apoptosis in the cells [95].…”

Section: Potential Treatments Targeting Cell-intrinsic Pathways Media...mentioning

confidence: 99%

Unraveling the dangerous duet between cancer cell plasticity and drug resistance

Chatterjee,

Pulipaka,

Subbalakshmi

et al. 2023

Comp Sys Onco

0

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Cancer cell plasticity is the ability of tumor cells to switch phenotypes and is one of the predominant requisites of cancer cells capable of undergoing metastasis. Cancer cell plasticity is also recognized as one of the major contributors to intratumoral heterogeneity, a critical factor underlying the progression of malignant tumors, which is known to modify tumor response and induce resistance against various modes of therapy, thus posing a barrier to efficient cancer management. Cancer cell plasticity is acquired by the subversion of cell signaling pathways like mitogen‐activated protein kinase pathway, phosphoinositide‐3‐kinase, signal transducer and activator of transcription 3, Wnt, Hedgehog and Notch as well as cellular programs such as epithelial to mesenchymal transition and phenotypic plasticity. This complex phenomenon has been studied in many cancer types like pancreatic cancer, colon cancer and breast cancer. This review will explore the current understanding we have in breast cancer on the intrinsic molecular mechanisms of cancer cell plasticity and the resistance to various types of cancer therapy that arise as a result of plasticity. We conclude by exploring the potential novel therapies that specifically target the pathways leading to plasticity and can be leveraged to treat patients living with the disease.

show abstract

AKT inhibitor AZD5363 suppresses stemness and promotes anti-cancer activity of 3,3′-diindolylmethane in human breast cancer cells

Cited by 7 publications

References 24 publications

Achieving a Deeper Understanding of Drug Metabolism and Responses Using Single-Cell Technologies

Achieving a Deeper Understanding of Drug Metabolism and Responses Using Single-Cell Technologies

The Unholy Trinity- Cancer cell plasticity, drug resistance and therapeutic opportunities

Unraveling the dangerous duet between cancer cell plasticity and drug resistance

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