Capsaicin triggers autophagic cell survival which drives epithelial mesenchymal transition and chemoresistance in bladder cancer cells in an Hedgehog-dependent manner

Amantini, Consuelo; Morelli, Maria Beatrice; Nabissi, Massimo; Cardinali, Claudio; Santoni, Matteo; Gismondi, Angela; Santoni, Giorgio

doi:10.18632/oncotarget.10326

Cited by 59 publications

(46 citation statements)

References 53 publications

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“…220 When the Hh ligand is present, it binds to PTCH, which changes the spatial conformation of PTCH, removing the inhibition of SMO activating the transcription factor GLI and inducing it to enter the cell nucleus, where GLI regulates cell growth, proliferation, and differentiation. 221 Studies have confirmed that abnormal activation of the Hh signaling pathway can be found in human cancers, 222 such as breast cancer, 223 lung cancer, 224 bladder cancer, 225 pancreatic cancer, 226 chondrosarcoma, 227 rhabdomyosarcoma, 228 neuroblastoma, 229 medulloblastoma, 230 and gastric cancer. 231 However, activation of Hh signaling is different in different tumors.…”

Section: Major Signaling Pathways In Cscsmentioning

confidence: 92%

Targeting cancer stem cell pathways for cancer therapy

Yang

Shi

Zhao

et al. 2020

Sig Transduct Target Ther

1,318

998

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Since cancer stem cells (CSCs) were first identified in leukemia in 1994, they have been considered promising therapeutic targets for cancer therapy. These cells have self-renewal capacity and differentiation potential and contribute to multiple tumor malignancies, such as recurrence, metastasis, heterogeneity, multidrug resistance, and radiation resistance. The biological activities of CSCs are regulated by several pluripotent transcription factors, such as OCT4, Sox2, Nanog, KLF4, and MYC. In addition, many intracellular signaling pathways, such as Wnt, NF-κB (nuclear factor-κB), Notch, Hedgehog, JAK-STAT (Janus kinase/signal transducers and activators of transcription), PI3K/AKT/mTOR (phosphoinositide 3-kinase/AKT/mammalian target of rapamycin), TGF (transforming growth factor)/SMAD, and PPAR (peroxisome proliferator-activated receptor), as well as extracellular factors, such as vascular niches, hypoxia, tumor-associated macrophages, cancer-associated fibroblasts, cancer-associated mesenchymal stem cells, extracellular matrix, and exosomes, have been shown to be very important regulators of CSCs. Molecules, vaccines, antibodies, and CAR-T (chimeric antigen receptor T cell) cells have been developed to specifically target CSCs, and some of these factors are already undergoing clinical trials. This review summarizes the characterization and identification of CSCs, depicts major factors and pathways that regulate CSC development, and discusses potential targeted therapy for CSCs.Signal Transduction and Targeted Therapy (2020) 5:8; https://doi.

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Section: Major Signaling Pathways In Cscsmentioning

confidence: 92%

Targeting cancer stem cell pathways for cancer therapy

Yang

Shi

Zhao

et al. 2020

Sig Transduct Target Ther

1,318

998

View full text Add to dashboard Cite

show abstract

“…It has been implicated in tumor growth and progression and explored as a potential therapeutic target [ 26 , 27 ]. Recently, a role for autophagy in capsaicin-induced cell death was proposed following reports indicating that capsaicin may induce autophagy, suggesting a promising therapeutic strategy for cancer [ 21 , 28 , 29 , 30 ]. However, only a few studies have examined capsaicin-induced apoptosis of NPC cells, and the effects of capsaicin on autophagic-associated pathways in NPC remain questionable.…”

Section: Introductionmentioning

confidence: 99%

Capsaicin Induces Autophagy and Apoptosis in Human Nasopharyngeal Carcinoma Cells by Downregulating the PI3K/AKT/mTOR Pathway

Lin

Wang

Hsu

et al. 2017

IJMS

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Capsaicin is a potential chemotherapeutic agent for different human cancers. In Southeast China, nasopharyngeal carcinoma (NPC) has the highest incidence of all cancers, but final treatment outcomes are unsatisfactory. However, there is a lack of information regarding the anticancer activity of capsaicin in NPC cells, and its effects on the signaling transduction pathways related to apoptosis and autophagy remain unclear. In the present study, the precise mechanisms by which capsaicin exerts anti-proliferative effects, cell cycle arrest, autophagy and apoptosis were investigated in NPC-TW01 cells. Exposure to capsaicin inhibited cancer cell growth and increased G1 phase cell cycle arrest. Western blotting and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) were used to measure capsaicin-induced autophagy via involvement of the class III PI3K/Beclin-1/Bcl-2 signaling pathway. Capsaicin induced autophagy by increasing levels of the autophagy markers LC3-II and Atg5, enhancing p62 and Fap-1 degradation and increasing caspase-3 activity to induce apoptosis, suggesting a correlation of blocking the PI3K/Akt/mTOR pathway with the above-mentioned anticancer activities. Taken together, these data confirm that capsaicin inhibited the growth of human NPC cells and induced autophagy, supporting its potential as a therapeutic agent for cancer.

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“…High doses of capsaicin induce autophagy, apoptosis, and inhibition of autophagy sensitized capsaicin-induced apoptosis in bladder [41] and liver cancer cells [42]. Although the autophagic parameters were not measured in the current study, autophagy could be considered as a potential mechanism of capsaicin's anti-cancer activity in human colon cancer cells.…”

Section: Anti-tumorigenic Effects Of Capsaicin In Colon Cancermentioning

confidence: 74%

Anti-Tumorigenic Effects of Capsaicin in Colon Cancer

Lee¹,

Clark²

2016

J Food Chem Nanotechnol

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Colon cancer is one of most common malignancies in the world. Capsaicin is a major component of chili peppers and has been shown to possess anti-cancer activity against various types of cancers. There is currently a limited number of preclinical studies that test the anti-cancer effects of capsaicin in colon cancer. The first objective of the present study is to investigate whether capsaicin influences tumor formation using a colon cancer mouse model. The second objective is to elucidate the anti-cancer mechanism of capsaicin using an in vitro cell culture system. For the in vivo study, we treated Apc Min+/ mice having truncated deletion of APC (adenomatous polyposis coli) with capsaicin. For the in vitro study, we exposed human colorectal cancer cell lines to different concentrations of capsaicin and performed western blot analysis. Oral gavage of capsaicin at a dose of 20 mg/ kg body weight for 4 weeks tended to decrease the number of polyps (43.5 ± 14.6 vs 27.8 ± 8.8, p = 0.114) and tumor load (78.6 ± 20.9 vs 47.4 ± 21.3, p = 0.083) in the intestine of Apc Min+/ mice. In vitro studies showed that, in human colon cancer cells, capsaicin induced phosphorylation of cyclin D1 at threonine 286 (T286) and decreased cyclin D1 expression in a dose-and time-dependent manner. In addition, capsaicin treatment increased intracellular ubiquitination of proteins in a dose-dependent manner and decreased the caspase-like activity of 20S proteasome significantly (p = 0.026). This study identifies capsaicin as a potential anti-cancer agent that targets cyclin D1 degradation and proteasome activity in colon cancer.

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Capsaicin triggers autophagic cell survival which drives epithelial mesenchymal transition and chemoresistance in bladder cancer cells in an Hedgehog-dependent manner

Cited by 59 publications

References 53 publications

Targeting cancer stem cell pathways for cancer therapy

Targeting cancer stem cell pathways for cancer therapy

Capsaicin Induces Autophagy and Apoptosis in Human Nasopharyngeal Carcinoma Cells by Downregulating the PI3K/AKT/mTOR Pathway

Anti-Tumorigenic Effects of Capsaicin in Colon Cancer

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