Capsaicin-Induced Death of Human Haematological Malignant Cell Lines Is Independent of TRPV1 Activation

Omari, Sofia; Adams, Murray J.; Kunde, Dale; Geraghty, Dominic P.

doi:10.1159/000445437

Cited by 14 publications

(9 citation statements)

References 29 publications

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“…TRPV1 antagonists, in addition to blocking the TRPV1 channel, exhibit different biological activities; for example, AMG517 causes hyperthermia [42], AMG9810 promotes mouse skin tumorigenesis [43], and capsazepine induces colorectal cancer apoptosis [44]. It was previously unclear whether capsaicin analogues could induce apoptosis via TRPV1dependent pathways [45,46]. Taken together, our results (i.e., TRPV1 antagonist capsazepine enhanced hyperthermia-induced apoptosis) support this hypothesis.…”

Section: Discussionsupporting

confidence: 74%

Mechanistic study of nonivamide enhancement of hyperthermia-induced apoptosis in U937 cells

Sun

Cui

Zakki

et al. 2018

Free Radical Biology and Medicine

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Hyperthermia is one therapeutic tool for damaging and killing cancer cells, with minimal injury to normal tissues. However, its cytotoxic effects alone are insufficient for quantitative cancer cell death. To overcome this limitation, several studies have explored non-toxic enhancers for hyperthermia-induced cell death. Capsaicin may be applicable as a therapeutic tool against various types of cancer. In the present study, we employed nonivamide, a less-pungent capsaicin analogue, to investigate its possible enhancing effects on hyperthermia-induced apoptosis; moreover, we analyzed its molecular mechanism. Treatment of U937 cells at 44 °C for 15 min, combined with nonivamide 50 μM, revealed enhancement of apoptosis. Significant increases in reactive oxygen species generation, mitochondrial dysfunction, and cleaved caspase-3 were observed during the combined treatment; these were accompanied by an increase in pro-apoptotic Bcl-2 family proteins and a decrease in anti-apoptotic Bcl-2 proteins. In addition, significant increases in p-JNK and p-p38 were detected, following the combined treatment. In conclusion, nonivamide enhanced hyperthermia-induced apoptosis via a mitochondrial-caspase dependent pathway. The underlying mechanism may include elevation of intracellular reactive oxygen species, mitochondrial dysfunction, and increased activation of JNK and p38.

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Section: Discussionsupporting

confidence: 74%

Mechanistic study of nonivamide enhancement of hyperthermia-induced apoptosis in U937 cells

Sun

Cui

Zakki

et al. 2018

Free Radical Biology and Medicine

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“…In contrast to the results from sciatic nerve, in the small intestine, the increase of F4/80 macrophages did not correlate proportionally with an increase of the TRPV1 receptor expression in the small intestine. This suggests a further TRPV1-independent effect of capsaicin which was described recently [ 58 , 59 ] and should be investigated in further studies. The pathways of p38 MAPK and MAPKAPK2 (MK2) are particularly interesting, because of their expression in immune cells.…”

Section: Discussionsupporting

confidence: 68%

Capsaicin-enriched diet ameliorates autoimmune neuritis in rats

Motte

Ambrosius

Grüter

et al. 2018

J Neuroinflammation

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BackgroundAutoimmune neuropathies are common PNS disorders and effective treatment is challenging. Environmental influence and dietary components are known to affect the course of autoimmune diseases. Capsaicin as pungent component of chili-peppers is common in human nutrition. An influence of capsaicin on autoimmune diseases has been postulated.MethodsWe tested capsaicin in the animal model of experimental autoimmune neuritis (EAN) in Lewis rat. Rats were immunized with P2-peptide and were treated with capsaicin in different preventive settings. Electrophysiological, histological, and molecular biological analyses of the sciatic nerve were performed to analyze T-cell and macrophage cell count, TRPV1, and cytokine expression. Moreover, FACS analyses including the intestinal immune system were executed.ResultsWe observed an immunomodulatory effect of an early preventive diet-concept, where a physiological dosage of oral capsaicin was given 10 days before immunization in EAN. A reduced inflammation of the sciatic nerve was significant detectable clinically, electrophysiologically (CMAPs reduced in control group p < 0.01; increase of nerve conduction blocks in control group p < 0.05), histologically (significant reduction of T-cells, macrophages and demyelination), and at cytokine level. In contrast, this therapeutic effect was missing with capsaicin given from the day of immunization onwards. As possible underlying mechanism, we were able to show changes in the expression of the capsaicin receptor in the sciatic nerve and the small intestine, as well as altered immune cell populations in the small intestine.ConclusionThis is the first report about the immunomodulatory effect of the common nutrient, capsaicin, in an experimental model for autoimmune neuropathies.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1165-x) contains supplementary material, which is available to authorized users.

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“…Of note, some studies have revealed that the effect of capsaicin was TRPV1 independent. For example, capsaicin was able to induce the death of cancer cells by activating the TRPV6 or CB1 channel (Lau et al, 2014;Omari et al, 2016). Therefore, alternative targets may also be involved in mediating the proapoptotic effect of capsaicin in melanoma, which needs to be further investigated.…”

Section: Discussionmentioning

confidence: 99%

Downregulated TRPV1 Expression Contributes to Melanoma Growth via the Calcineurin-ATF3-p53 Pathway

Yang

Guo

et al. 2018

Journal of Investigative Dermatology

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Melanoma is the most lethal form of skin cancer with increasing incidence over the years. Because of its rapid proliferative and drastic metastatic capacity, the prognosis of melanoma remains dismal, although the targeted therapy and immunotherapy have gained revolutionary progress recently. Therefore, it is of necessity to further clarify the mechanism of melanoma pathogenesis for developing an alternative treatment strategy. Transient receptor potential vanilloid 1 (TRPV1) is a nonselective Ca channel greatly involved in regulating cell apoptosis, proliferation, metabolism, and cancer development, but its role in melanoma remains unknown. Herein, we first found that TRPV1 expression was significantly decreased in melanoma tissues and cell lines, compared with nevus tissues and normal melanocytes, respectively. We then proved that TRPV1 overexpression or its agonist capsaicin treatment inhibited melanoma growth by activating p53 and inducing cell apoptosis. A subsequent mechanistic study revealed that TRPV1 induced Ca influx to regulate p53 activation via calcineurin-ATF3 transcriptional cascade. Finally, the effect of TRPV1 on melanoma growth was proved in vivo. Altogether, our study demonstrates that TRPV1 is a potential tumor suppressor in melanoma.

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Capsaicin-Induced Death of Human Haematological Malignant Cell Lines Is Independent of TRPV1 Activation

Cited by 14 publications

References 29 publications

Mechanistic study of nonivamide enhancement of hyperthermia-induced apoptosis in U937 cells

Mechanistic study of nonivamide enhancement of hyperthermia-induced apoptosis in U937 cells

Capsaicin-enriched diet ameliorates autoimmune neuritis in rats

Downregulated TRPV1 Expression Contributes to Melanoma Growth via the Calcineurin-ATF3-p53 Pathway

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