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Oxidant-based anticancer activity of a novel synthetic analogue of capsaicin, capsaicin epoxide

Lewinska, Anna; Chochrek, Pawel; Smolag, Karolina LU ; Rawska, Ewa and Wnuk, Maciej (2015) In Redox Biology 20(3). p.25-116
Abstract

OBJECTIVES: Plant-derived natural substances, such as capsaicin, with potent antiproliferative activity against cancer cells in vitro are considered to be promising nutraceuticals in anticancer therapy. Nevertheless, the limited systemic bioavailability of phytochemicals may raise questions regarding the physiological relevance of their phytochemical effects in vivo. Thus, the search for novel phytochemical-based substances with more efficient anticancer action is needed.

METHODS: In the present study, a capsaicin analogue, namely, capsaicin epoxide, was synthesized, and its cytotoxic potential against cancer cells was evaluated and compared to that of capsaicin through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide... (More)

OBJECTIVES: Plant-derived natural substances, such as capsaicin, with potent antiproliferative activity against cancer cells in vitro are considered to be promising nutraceuticals in anticancer therapy. Nevertheless, the limited systemic bioavailability of phytochemicals may raise questions regarding the physiological relevance of their phytochemical effects in vivo. Thus, the search for novel phytochemical-based substances with more efficient anticancer action is needed.

METHODS: In the present study, a capsaicin analogue, namely, capsaicin epoxide, was synthesized, and its cytotoxic potential against cancer cells was evaluated and compared to that of capsaicin through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and multi-caspase assays. The abilities of capsaicin and capsaicin epoxide to induce oxidative stress were estimated using redox-sensitive fluorogenic probes: 2',7'-dichlorodihydrofluorescein diacetate (H2DCF-DA) and dihydroethidium.

RESULTS: The structure and purity of the synthesized product were confirmed by nuclear magnetic resonance spectroscopy, electrospray ionization mass spectrometry, and gas chromatography. Normal human dermal fibroblasts were not susceptible to treatment with the agent, whereas a cancer cell type-specific response was observed. Human breast carcinoma cells were found to be the most sensitive to capsaicin epoxide treatment compared with capsaicin treatment, and the action of capsaicin epoxide was oxidant based.

DISCUSSION: Our data indicate that the antiproliferative activity of capsaicin epoxide is potentiated in vitro, when used at much lower concentrations compared with capsaicin at similar concentrations. Thus, the findings of this study may have implications for phytochemical-based anticancer drug development.

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publishing date
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Contribution to journal
publication status
published
keywords
Animals, Antineoplastic Agents, Phytogenic, Apoptosis, Capsaicin, Cell Line, Tumor, Chemistry Techniques, Synthetic, Drug Screening Assays, Antitumor, Fluoresceins, Humans, MCF-7 Cells, Magnetic Resonance Spectroscopy, Mice, NIH 3T3 Cells, Oxidants, Oxidative Stress, Reactive Oxygen Species, Journal Article, Research Support, Non-U.S. Gov't
in
Redox Biology
volume
20
issue
3
pages
25 - 116
publisher
Elsevier
external identifiers
  • scopus:84926292980
ISSN
2213-2317
DOI
10.1179/1351000214Y.0000000113
language
English
LU publication?
no
id
bd2b7a67-2c34-4f8a-99c2-2d130cf40786
date added to LUP
2017-06-01 09:54:38
date last changed
2017-08-27 06:41:43
@article{bd2b7a67-2c34-4f8a-99c2-2d130cf40786,
  abstract     = {<p>OBJECTIVES: Plant-derived natural substances, such as capsaicin, with potent antiproliferative activity against cancer cells in vitro are considered to be promising nutraceuticals in anticancer therapy. Nevertheless, the limited systemic bioavailability of phytochemicals may raise questions regarding the physiological relevance of their phytochemical effects in vivo. Thus, the search for novel phytochemical-based substances with more efficient anticancer action is needed.</p><p>METHODS: In the present study, a capsaicin analogue, namely, capsaicin epoxide, was synthesized, and its cytotoxic potential against cancer cells was evaluated and compared to that of capsaicin through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and multi-caspase assays. The abilities of capsaicin and capsaicin epoxide to induce oxidative stress were estimated using redox-sensitive fluorogenic probes: 2',7'-dichlorodihydrofluorescein diacetate (H2DCF-DA) and dihydroethidium.</p><p>RESULTS: The structure and purity of the synthesized product were confirmed by nuclear magnetic resonance spectroscopy, electrospray ionization mass spectrometry, and gas chromatography. Normal human dermal fibroblasts were not susceptible to treatment with the agent, whereas a cancer cell type-specific response was observed. Human breast carcinoma cells were found to be the most sensitive to capsaicin epoxide treatment compared with capsaicin treatment, and the action of capsaicin epoxide was oxidant based.</p><p>DISCUSSION: Our data indicate that the antiproliferative activity of capsaicin epoxide is potentiated in vitro, when used at much lower concentrations compared with capsaicin at similar concentrations. Thus, the findings of this study may have implications for phytochemical-based anticancer drug development.</p>},
  author       = {Lewinska, Anna and Chochrek, Pawel and Smolag, Karolina and Rawska, Ewa and Wnuk, Maciej},
  issn         = {2213-2317},
  keyword      = {Animals,Antineoplastic Agents, Phytogenic,Apoptosis,Capsaicin,Cell Line, Tumor,Chemistry Techniques, Synthetic,Drug Screening Assays, Antitumor,Fluoresceins,Humans,MCF-7 Cells,Magnetic Resonance Spectroscopy,Mice,NIH 3T3 Cells,Oxidants,Oxidative Stress,Reactive Oxygen Species,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {3},
  pages        = {25--116},
  publisher    = {Elsevier},
  series       = {Redox Biology},
  title        = {Oxidant-based anticancer activity of a novel synthetic analogue of capsaicin, capsaicin epoxide},
  url          = {http://dx.doi.org/10.1179/1351000214Y.0000000113},
  volume       = {20},
  year         = {2015},
}