Capsaicin reactivates hMOF in gastric cancer cells and induces cell growth inhibition

Wang, Fei; Zhao, Jiayao; Liu, Da; Zhao, Tong; Lu, Zeming; Zhu, Lin; Cao, Lingling; Yang, Jiaxing; Jin, Jingji; Cai, Yong

doi:10.1080/15384047.2016.1235654

Cited by 32 publications

(22 citation statements)

References 48 publications

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“…The members of this family are responsible for post-translationally modifying histones and nonhistone proteins [31,32]. Few previous studies have examined the association between capsaicin and SIRT1, and even fewer have assessed their role in growth regulation [33,34,35]. We previously reported that tNOX knockdown in T24 cells reversed cancer phenotypes in association with downregulation of SIRT1 and cyclin D1, even though the details of the underlying mechanism remained unclear [19].…”

Section: Discussionmentioning

confidence: 99%

Capsaicin Targets tNOX (ENOX2) to Inhibit G1 Cyclin/CDK Complex, as Assessed by the Cellular Thermal Shift Assay (CETSA)

Islam

Zeng

et al. 2019

Cells

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Capsaicin (8-methyl-N-vanillyl-6-noneamide), which is an active component in red chili peppers, is used as a chemopreventive agent that shows favorable cytotoxicity against cancer cells. Accumulating evidence indicates that capsaicin preferentially inhibits a tumor-associated NADH oxidase (tNOX, ENOX2) that is ubiquitously expressed in cancer but not in non-transformed cells. This attenuates cancer cell growth by inducing apoptosis. The capsaicin-mediated inhibition of tNOX was recently shown to prolong the cell cycle. However, the molecular events underlying this regulation have not yet been investigated. In the present study, we used a cellular thermal shift assay (CETSA) to detect “target engagement” of capsaicin and its consequent impact on cell cycle progression. Our results indicated that capsaicin engaged with tNOX and triggered the proteasomal degradation of tNOX, which leads to the inhibition of NAD+-dependent SIRT1 deacetylase. Ultimately, the acetylation levels of c-Myc and p53 were enhanced, which suppressed the activation of G1 cyclin/Cyclin-dependent kinase complexes and triggered cell cycle arrest in cancer cells. The results obtained when tNOX was overexpressed in non-cancer cells validated its importance in cell cycle progression. These findings provide the first molecular insights into the regulatory role of tNOX and the anti-proliferative property of capsaicin in regulating the cell cycle of bladder cancer cells.

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Section: Discussionmentioning

confidence: 99%

Capsaicin Targets tNOX (ENOX2) to Inhibit G1 Cyclin/CDK Complex, as Assessed by the Cellular Thermal Shift Assay (CETSA)

Islam

Zeng

et al. 2019

Cells

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“…Capsaicin targets some signaling pathways involved in carcinogenesis and tumor invasion, but its global impact is not entirely known, despite the observation that it may disturb cancer cell metabolism [ 28 ] implying some anti-neoplastic biologic effects. However, in most cases, this action on cancer cells’ metabolism seems to be independent of TRPV1 [ 29 ].…”

Section: Capsaicin In Gastrointestinal Cancermentioning

confidence: 99%

“…A recent study by Wang et al showed a new epigenetic action of capsaicin capable of regulating cell growth in gastric cancer [ 28 ]. The authors showed that capsaicin promotes the activity of histone acetyltransferase hMOF inducing a positive feedback loop ending in cell cycle arrest and apoptosis in SGC-7901 and MGC-803 gastric cancer cells.…”

Section: Capsaicin In Gastrointestinal Cancermentioning

confidence: 99%

The Effects of Capsaicin on Gastrointestinal Cancers

et al. 2020

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Gastrointestinal (GI) cancers are a group of diseases with very high positions in the ranking of cancer incidence and mortality. While they show common features regarding the molecular mechanisms involved in cancer development, organ-specific pathophysiological processes may trigger distinct signaling pathways and intricate interactions with inflammatory cells from the tumoral milieu and mediators involved in tumorigenesis. The treatment of GI cancers is a topic of increasing interest due to the severity of these diseases, their impact on the patients’ survivability and quality of life, and the burden they set on the healthcare system. As the efficiency of existing drugs is hindered by chemoresistance and adverse reactions when administered in high doses, new therapies are sought, and emerging drugs, formulations, and substance synergies are the focus of a growing number of studies. A class of chemicals with great potential through anti-inflammatory, anti-oxidant, and anti-tumoral effects is phytochemicals, and capsaicin in particular is the subject of intensive research looking to validate its position in complementing cancer treatment. Our paper thoroughly reviews the available scientific evidence concerning the effects of capsaicin on major GI cancers and its interactions with the molecular pathways involved in the course of these diseases.

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“…[11][12][13] Unlike the above findings, more studies have provided evidence that CAP is a potential anti-tumour compound in a wide variety of cancer types, including breast cancer, lung cancer, gastric cancer, liver cancer, prostate cancer and bladder cancer, and so on. [14][15][16][17][18][19][20] There may be more complex molecular biology events behind these contradictory views of CAP. In addition, when combined with certain chemotherapeutic drugs such as 5-Fu, cisplatin, and pirarubicin, CAP can enhance the anti-tumour activity of these drugs, [21][22][23] suggesting that CAP has broad application prospects and may be used as a potential chemopreventive and therapeutic drug for cancer.…”

Section: What Is K Nown and Objec Tivementioning

confidence: 99%

“…23 CAP also induces cell growth inhibition by reactivating hMOF and associated H4K16ac. 15 In the study of apoptosis, CAP induces apoptosis in human gastric cancer cells AGS in the presence of p53 47 or by modulating MAPK signalling pathway. 48 which is associated with the late apoptotic extracellular passive release of HMGB1, HSP70 and HSP90, the second line of hallmarks required for ICD.…”

Section: Stomach Cancermentioning

confidence: 99%

Application of capsaicin as a potential new therapeutic drug in human cancers

et al. 2019

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What is known and objective: Capsaicin, the major active ingredient of chili pepper, may play a "dual role" in tumourigenesis, acting as a carcinogen or as a cancer preventive agent. The aim of this study was to investigate the anticancer mechanisms of capsaicin and the effects of capsaicin on traditional chemotherapeutic drugs and radiotherapy in various cancer types and the potential for clinical application in cancer therapy. Methods: We conducted extensive literature searches through PubMed to collect representative studies of capsaicin in different cancer types. These studies investigated the anticancer molecular mechanisms of capsaicin.

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Capsaicin reactivates hMOF in gastric cancer cells and induces cell growth inhibition

Cited by 32 publications

References 48 publications

Capsaicin Targets tNOX (ENOX2) to Inhibit G1 Cyclin/CDK Complex, as Assessed by the Cellular Thermal Shift Assay (CETSA)

Capsaicin Targets tNOX (ENOX2) to Inhibit G1 Cyclin/CDK Complex, as Assessed by the Cellular Thermal Shift Assay (CETSA)

The Effects of Capsaicin on Gastrointestinal Cancers

Application of capsaicin as a potential new therapeutic drug in human cancers

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