Phenethyl isothiocyanate hampers growth and progression of HER2-positive breast and ovarian carcinoma by targeting their stem cell compartment

Koschorke, Ada; Faraci, Simona; Giani, Debora; Chiodoni, Claudia; Iorio, Egidio; Canese, Rossella; Colombo, Mario P.; Lamolinara, Alessia; Iezzi, Manuela; Ladomery, Michael; Vernieri, Claudio; Braud, Filippo de; Nicola, Massimo Di; Tagliabue, Elda; Castagnoli, Lorenzo; Pupa, Serenella M.

doi:10.1007/s13402-019-00464-w

Cited by 13 publications

(12 citation statements)

References 55 publications

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“…Phenethyl isothiocyanate (PEITC), a cruciferous-vegetables-derived isothiocyanate, suppressed Notch-1 and Notch-2 levels, reduced cell proliferation, and induced apoptosis in pancreatic cancer cells [ 59 ]. In HER2-positive breast and ovarian carcinoma cells, PEITC decreased the expression of NICD-1 and targeted both differentiated cells and CSCs [ 58 ].…”

Section: Modulation Of Notch Pathway By Dietary Agentsmentioning

confidence: 99%

Modulation of Notch Signaling Pathway by Bioactive Dietary Agents

Kiesel

Stan

2022

IJMS

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Notch signaling is often aberrantly activated in solid and hematological cancers and regulates cell fate decisions and the maintenance of cancer stem cells. In addition, increased expression of Notch pathway components is clinically associated with poorer prognosis in several types of cancer. Targeting Notch may have chemopreventive and anti-cancer effects, leading to reduced disease incidence and improved survival. While therapeutic agents are currently in development to achieve this goal, several researchers have turned their attention to dietary and natural agents for targeting Notch signaling. Given their natural abundance from food sources, the use of diet-derived agents to target Notch signaling offers the potential advantage of low toxicity to normal tissue. In this review, we discuss several dietary agents including curcumin, EGCG, resveratrol, and isothiocyanates, which modulate Notch pathway components in a context-dependent manner. Dietary agents modulate Notch signaling in several types of cancer and concurrently decrease in vitro cell viability and in vivo tumor growth, suggesting a potential role for their clinical use to target Notch pathway components, either alone or in combination with current therapeutic agents.

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Section: Modulation Of Notch Pathway By Dietary Agentsmentioning

confidence: 99%

Modulation of Notch Signaling Pathway by Bioactive Dietary Agents

Kiesel

Stan

2022

IJMS

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“…Phenethyl isothiocyanate (PEITC) is a natural product present in many cruciferous vegetables with anti‐cancer and chemopreventive activities in clinical trials and has been associated with the induction of oxidative stress [ 60 ]. Interestingly, PEITC has also been reported to be able to eliminate CSCs of different types of cancer, including cervical [ 61 , 62 ], lung [ 63 ], ovarian [ 64 ], and breast cancers [ 64 , 65 ]. Importantly, PEITC inhibited the properties of CRC‐SCs through downregulation of the Wnt/β‐catenin pathway, inhibition of proliferation, and induction of apoptosis in CRC DLD‐1 and SW480 cell lines.…”

Section: Cell Signaling Pathwaysmentioning

confidence: 99%

Emerging agents that target signaling pathways to eradicate colorectal cancer stem cells

Silva

Santos

Dias

et al. 2021

Cancer Communications

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Colorectal cancer (CRC) represents the third most commonly diagnosed cancer and the second leading cause of cancer death worldwide. The modern concept of cancer biology indicates that cancer is formed of a small population of cells called cancer stem cells (CSCs), which present both pluripotency and self‐renewal properties. These cells are considered responsible for the progression of the disease, recurrence and tumor resistance. Interestingly, some cell signaling pathways participate in CRC survival, proliferation, and self‐renewal properties, and most of them are dysregulated in CSCs, including the Wingless (Wnt)/β‐catenin, Notch, Hedgehog, nuclear factor kappa B (NF‐κB), Janus kinase/signal transducer and activator of transcription (JAK/STAT), peroxisome proliferator‐activated receptor (PPAR), phosphatidyl‐inositol‐3‐kinase/Akt/mechanistic target of rapamycin (PI3K/Akt/mTOR), and transforming growth factor‐β (TGF‐β)/Smad pathways. In this review, we summarize the strategies for eradicating CRC stem cells by modulating these dysregulated pathways, which will contribute to the study of potential therapeutic schemes, combining conventional drugs with CSC‐targeting drugs, and allowing better cure rates in anti‐CRC therapy.

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“…PEITC has been reported to target CSC compartments in a variety of cancers, including cervical cancer [53], colon cancer [33], colorectal cancer [54], and HeLa cancer cells [10]. Recently, Koschorke et al (2019) found that PEITC can target HER-2 positive BCSCs, and this effect was enhanced in combination with trastuzumab therapy [55]. Moreover, Western blot analysis revealed that PEITC can reduce levels of CD44, Oct3/4, and MRP-1, which are widely used as BCSC markers (Figure 7a).…”

Section: Discussionmentioning

confidence: 99%

Phenethyl Isothiocyanate Suppresses Stemness in the Chemo- and Radio-Resistant Triple-Negative Breast Cancer Cell Line MDA-MB-231/IR Via Downregulation of Metadherin

Nguyen

Moon

Ediriweera

et al. 2020

Cancers

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Resistance to chemotherapy and radiation therapy is considered a major therapeutic barrier in breast cancer. Cancer stem cells (CSCs) play a prominent role in chemo and radiotherapy resistance. The established chemo and radio-resistant triple-negative breast cancer (TNBC) cell line MDA-MB-231/IR displays greater CSC characteristics than the parental MDA-MB-231 cells. Escalating evidence demonstrates that metadherin (MTDH) is associated with a number of cancer signaling pathways as well as breast cancer therapy resistance, making it an attractive therapeutic target. Kaplan–Meier plot analysis revealed a correlation between higher levels of MTDH and shorter lifetimes in breast cancer and TNBC patients. Moreover, there was a positive correlation between the MTDH and CD44 expression levels in The Cancer Genome Atlas breast cancer database. We demonstrate that MTDH plays a pivotal role in the regulation of stemness in MDA-MB-231/IR cells. Knockdown of MTDH in MDA-MB-231/IR cells resulted in a reduction in the CSC population, aldehyde dehydrogenase activity, and major CSC markers, including β-catenin, CD44+, and Slug. In addition, MTDH knockdown increased reactive oxygen species (ROS) levels in MDA-MB-231/IR cells. We found that phenethyl isothiocyanate (PEITC), a well-known pro-oxidant phytochemical, suppressed stemness in MDA-MB-231/IR cells through ROS modulation via the downregulation of MTDH. Co-treatment of PEITC and N-Acetylcysteine (a ROS scavenger) caused alterations in PEITC induced cell death and CSC markers. Moreover, PEITC regulated MTDH expression at the post-transcriptional level, which was confirmed using cycloheximide, a protein synthesis inhibitor.

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Phenethyl isothiocyanate hampers growth and progression of HER2-positive breast and ovarian carcinoma by targeting their stem cell compartment

Cited by 13 publications

References 55 publications

Modulation of Notch Signaling Pathway by Bioactive Dietary Agents

Modulation of Notch Signaling Pathway by Bioactive Dietary Agents

Emerging agents that target signaling pathways to eradicate colorectal cancer stem cells

Phenethyl Isothiocyanate Suppresses Stemness in the Chemo- and Radio-Resistant Triple-Negative Breast Cancer Cell Line MDA-MB-231/IR Via Downregulation of Metadherin

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