The Mitochondrial Ca2+ Overload via Voltage-Gated Ca2+ Entry Contributes to an Anti-Melanoma Effect of Diallyl Trisulfide
| Autor: | Toyoko Ochiai, Chinatsu Nakagawa, Yoshihiro Suzuki-Karasaki, Manami Suzuki-Karasaki, Miki Suzuki-Karasaki |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
mitochondrial Ca2+ Pharmacology Catalysis Melittin Calcium in biology lcsh:Chemistry Inorganic Chemistry 03 medical and health sciences chemistry.chemical_compound acidification 0302 clinical medicine TheoryofComputation_ANALYSISOFALGORITHMSANDPROBLEMCOMPLEXITY Extracellular melanoma Channel blocker Physical and Theoretical Chemistry voltage-gated Ca2+ channel lcsh:QH301-705.5 Molecular Biology Spectroscopy Ca2+ channel blocker Voltage-gated ion channel Organic Chemistry apoptosis food and beverages General Medicine diallyl trisulfide Computer Science Applications 030104 developmental biology Diallyl trisulfide lcsh:Biology (General) lcsh:QD1-999 chemistry melittin Apoptosis 030220 oncology & carcinogenesis store-operated Ca2+ channel Intracellular |
| Zdroj: | International Journal of Molecular Sciences Volume 21 Issue 2 International Journal of Molecular Sciences, Vol 21, Iss 2, p 491 (2020) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms21020491 |
| Popis: | Allium vegetables such as garlic (Allium sativum L.) are rich in organosulfur compounds that prevent human chronic diseases, including cancer. Of these, diallyl trisulfide (DATS) exhibits anticancer effects against a variety of tumors, including malignant melanoma. Although previous studies have shown that DATS increases intracellular calcium (Ca2+) in different cancer cell types, the role of Ca2+ in the anticancer effect is obscure. In the present study, we investigated the Ca2+ pathways involved in the anti-melanoma effect. We used melittin, the bee venom that can activate a store-operated Ca2+ entry (SOCE) and apoptosis, as a reference. DATS increased apoptosis in human melanoma cell lines in a Ca2+-dependent manner. It also induced mitochondrial Ca2+ (Ca2+mit) overload through intracellular and extracellular Ca2+ fluxes independently of SOCE. Strikingly, acidification augmented Ca2+mit overload, and Ca2+ channel blockers reduced the effect more significantly under acidic pH conditions. On the contrary, acidification mitigated SOCE and Ca2+mit overload caused by melittin. Finally, Ca2+ channel blockers entirely inhibited the anti-melanoma effect of DATS. Our findings suggest that DATS explicitly evokes Ca2+mit overload via a non-SOCE, thereby displaying the anti-melanoma effect. |
| Databáze: | OpenAIRE |
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