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


CONCLUSIONS
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.
Anna
A
Lewinska
Pawel
P
Chochrek
Karolina
K
Smolag
Ewa
E
Rawska
Maciej
M
Wnuk
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D004354:Drug Screening Assays, Antitumor; D005452:Fluoresceins; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D041681:NIH 3T3 Cells / Q000187:drug effects; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
C110400:2',7'-dichlorodihydrofluorescein diacetate; D000972:Antineoplastic Agents, Phytogenic; D005452:Fluoresceins; D016877:Oxidants; D017382:Reactive Oxygen Species; D002211:Capsaicin
Anticancer activity; Capsaicin; Capsaicin epoxide; Oxidative stress