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The Mitochondrial Ca 2+ Overload via Voltage-Gated Ca 2+ Entry Contributes to an Anti-Melanoma Effect of Diallyl Trisulfide
vegetables such as garlic ( 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 increase...
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| Published in: | International journal of molecular sciences 2020-01, Vol.21 (2) |
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| Main Authors: | , , , , |
| Format: | Article |
| Language: | English |
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| container_issue | 2 |
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| container_title | International journal of molecular sciences |
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| creator | Nakagawa, Chinatsu Suzuki-Karasaki, Manami Suzuki-Karasaki, Miki Ochiai, Toyoko Suzuki-Karasaki, Yoshihiro |
| description | vegetables such as garlic (
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 (Ca
) in different cancer cell types, the role of Ca
in the anticancer effect is obscure. In the present study, we investigated the Ca
pathways involved in the anti-melanoma effect. We used melittin, the bee venom that can activate a store-operated Ca
entry (SOCE) and apoptosis, as a reference. DATS increased apoptosis in human melanoma cell lines in a Ca
-dependent manner. It also induced mitochondrial Ca
(Ca
) overload through intracellular and extracellular Ca
fluxes independently of SOCE. Strikingly, acidification augmented Ca
overload, and Ca
channel blockers reduced the effect more significantly under acidic pH conditions. On the contrary, acidification mitigated SOCE and Ca
overload caused by melittin. Finally, Ca
channel blockers entirely inhibited the anti-melanoma effect of DATS. Our findings suggest that DATS explicitly evokes Ca
overload via a non-SOCE, thereby displaying the anti-melanoma effect. |
| doi_str_mv | 10.3390/ijms21020491 |
| format | article |
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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 (Ca
) in different cancer cell types, the role of Ca
in the anticancer effect is obscure. In the present study, we investigated the Ca
pathways involved in the anti-melanoma effect. We used melittin, the bee venom that can activate a store-operated Ca
entry (SOCE) and apoptosis, as a reference. DATS increased apoptosis in human melanoma cell lines in a Ca
-dependent manner. It also induced mitochondrial Ca
(Ca
) overload through intracellular and extracellular Ca
fluxes independently of SOCE. Strikingly, acidification augmented Ca
overload, and Ca
channel blockers reduced the effect more significantly under acidic pH conditions. On the contrary, acidification mitigated SOCE and Ca
overload caused by melittin. Finally, Ca
channel blockers entirely inhibited the anti-melanoma effect of DATS. Our findings suggest that DATS explicitly evokes Ca
overload via a non-SOCE, thereby displaying the anti-melanoma effect.</description><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms21020491</identifier><identifier>PMID: 31940976</identifier><language>eng</language><publisher>Switzerland</publisher><subject>Allyl Compounds - pharmacology ; Calcium - metabolism ; Calcium Channel Blockers - pharmacology ; Calcium Channels - metabolism ; Cell Line, Tumor ; Humans ; Melanoma - drug therapy ; Melanoma - metabolism ; Melanoma - pathology ; Melanoma, Cutaneous Malignant ; Mitochondria - metabolism ; Mitochondria - pathology ; Neoplasm Proteins - antagonists & inhibitors ; Neoplasm Proteins - metabolism ; Skin Neoplasms - drug therapy ; Skin Neoplasms - metabolism ; Skin Neoplasms - pathology ; Sulfides - pharmacology</subject><ispartof>International journal of molecular sciences, 2020-01, Vol.21 (2)</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0003-1158-178X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31940976$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nakagawa, Chinatsu</creatorcontrib><creatorcontrib>Suzuki-Karasaki, Manami</creatorcontrib><creatorcontrib>Suzuki-Karasaki, Miki</creatorcontrib><creatorcontrib>Ochiai, Toyoko</creatorcontrib><creatorcontrib>Suzuki-Karasaki, Yoshihiro</creatorcontrib><title>The Mitochondrial Ca 2+ Overload via Voltage-Gated Ca 2+ Entry Contributes to an Anti-Melanoma Effect of Diallyl Trisulfide</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>vegetables such as garlic (
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 (Ca
) in different cancer cell types, the role of Ca
in the anticancer effect is obscure. In the present study, we investigated the Ca
pathways involved in the anti-melanoma effect. We used melittin, the bee venom that can activate a store-operated Ca
entry (SOCE) and apoptosis, as a reference. DATS increased apoptosis in human melanoma cell lines in a Ca
-dependent manner. It also induced mitochondrial Ca
(Ca
) overload through intracellular and extracellular Ca
fluxes independently of SOCE. Strikingly, acidification augmented Ca
overload, and Ca
channel blockers reduced the effect more significantly under acidic pH conditions. On the contrary, acidification mitigated SOCE and Ca
overload caused by melittin. Finally, Ca
channel blockers entirely inhibited the anti-melanoma effect of DATS. Our findings suggest that DATS explicitly evokes Ca
overload via a non-SOCE, thereby displaying the anti-melanoma effect.</description><subject>Allyl Compounds - pharmacology</subject><subject>Calcium - metabolism</subject><subject>Calcium Channel Blockers - pharmacology</subject><subject>Calcium Channels - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Humans</subject><subject>Melanoma - drug therapy</subject><subject>Melanoma - metabolism</subject><subject>Melanoma - pathology</subject><subject>Melanoma, Cutaneous Malignant</subject><subject>Mitochondria - metabolism</subject><subject>Mitochondria - pathology</subject><subject>Neoplasm Proteins - antagonists & inhibitors</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Skin Neoplasms - drug therapy</subject><subject>Skin Neoplasms - metabolism</subject><subject>Skin Neoplasms - pathology</subject><subject>Sulfides - pharmacology</subject><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNqFjr9LAzEYQIMgtlY3Z_l2Oc2PsyWjnGddisvRtXxtvtiUXFKSXOHwn7dDnZ3e8ng8xh4Ef1ZK8xd36LMUXPJaiys2FbWUFefzxYTd5nzgXCr5qm_YRAldc72YT9lPtydYuRJ3-xhMcuihQZBP8HWi5CMaODmEdfQFv6laYiFzEdpQ0ghNPMNth0IZSgQM8BaKq1bkMcQeobWWdgWihfdz248euuTy4K0zdMeuLfpM9xfO2ONH2zWf1XHY9mQ2x-R6TOPm71b9K_wCuf5O0w</recordid><startdate>20200113</startdate><enddate>20200113</enddate><creator>Nakagawa, Chinatsu</creator><creator>Suzuki-Karasaki, Manami</creator><creator>Suzuki-Karasaki, Miki</creator><creator>Ochiai, Toyoko</creator><creator>Suzuki-Karasaki, Yoshihiro</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><orcidid>https://orcid.org/0000-0003-1158-178X</orcidid></search><sort><creationdate>20200113</creationdate><title>The Mitochondrial Ca 2+ Overload via Voltage-Gated Ca 2+ Entry Contributes to an Anti-Melanoma Effect of Diallyl Trisulfide</title><author>Nakagawa, Chinatsu ; Suzuki-Karasaki, Manami ; Suzuki-Karasaki, Miki ; Ochiai, Toyoko ; Suzuki-Karasaki, Yoshihiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-pubmed_primary_319409763</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Allyl Compounds - pharmacology</topic><topic>Calcium - metabolism</topic><topic>Calcium Channel Blockers - pharmacology</topic><topic>Calcium Channels - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Humans</topic><topic>Melanoma - drug therapy</topic><topic>Melanoma - metabolism</topic><topic>Melanoma - pathology</topic><topic>Melanoma, Cutaneous Malignant</topic><topic>Mitochondria - metabolism</topic><topic>Mitochondria - pathology</topic><topic>Neoplasm Proteins - antagonists & inhibitors</topic><topic>Neoplasm Proteins - metabolism</topic><topic>Skin Neoplasms - drug therapy</topic><topic>Skin Neoplasms - metabolism</topic><topic>Skin Neoplasms - pathology</topic><topic>Sulfides - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nakagawa, Chinatsu</creatorcontrib><creatorcontrib>Suzuki-Karasaki, Manami</creatorcontrib><creatorcontrib>Suzuki-Karasaki, Miki</creatorcontrib><creatorcontrib>Ochiai, Toyoko</creatorcontrib><creatorcontrib>Suzuki-Karasaki, Yoshihiro</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nakagawa, Chinatsu</au><au>Suzuki-Karasaki, Manami</au><au>Suzuki-Karasaki, Miki</au><au>Ochiai, Toyoko</au><au>Suzuki-Karasaki, Yoshihiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Mitochondrial Ca 2+ Overload via Voltage-Gated Ca 2+ Entry Contributes to an Anti-Melanoma Effect of Diallyl Trisulfide</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2020-01-13</date><risdate>2020</risdate><volume>21</volume><issue>2</issue><eissn>1422-0067</eissn><abstract>vegetables such as garlic (
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 (Ca
) in different cancer cell types, the role of Ca
in the anticancer effect is obscure. In the present study, we investigated the Ca
pathways involved in the anti-melanoma effect. We used melittin, the bee venom that can activate a store-operated Ca
entry (SOCE) and apoptosis, as a reference. DATS increased apoptosis in human melanoma cell lines in a Ca
-dependent manner. It also induced mitochondrial Ca
(Ca
) overload through intracellular and extracellular Ca
fluxes independently of SOCE. Strikingly, acidification augmented Ca
overload, and Ca
channel blockers reduced the effect more significantly under acidic pH conditions. On the contrary, acidification mitigated SOCE and Ca
overload caused by melittin. Finally, Ca
channel blockers entirely inhibited the anti-melanoma effect of DATS. Our findings suggest that DATS explicitly evokes Ca
overload via a non-SOCE, thereby displaying the anti-melanoma effect.</abstract><cop>Switzerland</cop><pmid>31940976</pmid><doi>10.3390/ijms21020491</doi><orcidid>https://orcid.org/0000-0003-1158-178X</orcidid></addata></record> |
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| ispartof | International journal of molecular sciences, 2020-01, Vol.21 (2) |
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| source | NCBI_PubMed Central（免费）; Publicly Available Content Database |
| subjects | Allyl Compounds - pharmacology Calcium - metabolism Calcium Channel Blockers - pharmacology Calcium Channels - metabolism Cell Line, Tumor Humans Melanoma - drug therapy Melanoma - metabolism Melanoma - pathology Melanoma, Cutaneous Malignant Mitochondria - metabolism Mitochondria - pathology Neoplasm Proteins - antagonists & inhibitors Neoplasm Proteins - metabolism Skin Neoplasms - drug therapy Skin Neoplasms - metabolism Skin Neoplasms - pathology Sulfides - pharmacology |
| title | The Mitochondrial Ca 2+ Overload via Voltage-Gated Ca 2+ Entry Contributes to an Anti-Melanoma Effect of Diallyl Trisulfide |
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