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Anticancer activities of vitamin K3 analogues.

Abstract

In a previous study we reported on the synthesis of 1,4-naphthoquinone-sulfides by thiolation of 1,4-naphthohydroquinones with primary aryl and alkyl thiols using laccase as catalyst. These compounds were synthesized as Vitamin K3 analogues. Vitamin K3 (VK3; 2-methyl-1,4-naphthoquinone; menadione) is known to have potent anticancer activity. This investigation reports on the anticancer activity of these VK3 analogues against TK10 renal, UACC62 melanoma, MCF7 breast, HeLa cervical, PC3 prostate and HepG2 liver cancer cell lines to evaluate their cytostatic effects. A 1,4-naphthohydroquinone derivative exhibited potent cytostatic effects (GI50 = 1.66-6.75 μM) which were better than that of etoposide and parthenolide against several of the cancer cell lines. This compound produces reactive oxygen species and disrupts the mitochondrial membrane potential in the MCF7 breast cancer cell line which is an indication that the cells undergo apoptosis. The 1,4-naphthoquinone sulfides also had potent cytostatic effects (GI50 = 2.82-9.79 μM) which were also better than that of etoposide, parthenolide and VK3 against several of the cancer cell lines. These compounds are generally more selective for cancer cells than for normal human lung fetal fibroblasts (WI-38). They also have moderate to weak cytostatic effects compared to etoposide, parthenolide and VK3 which have potent cytostatic effects against WI-38. One analogue induces apoptosis by activating caspases without arresting the cell cycle in the MCF7 breast cancer cell line. These results inspire further research for possible application in cancer chemotherapy.

Authors+Show Affiliations

CSIR Biosciences, P O Box 395, Pretoria, South Africa. kwwellington@gmail.com.Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Gauteng, South Africa. Centre for HIV and STI's, National Institute for Communicable Diseases, Johannesburg, Gauteng, South Africa.CSIR Biosciences, P O Box 395, Pretoria, South Africa.School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, 2050, South Africa.School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, 2050, South Africa.Department of Biochemistry, University of Johannesburg, PO Box 524, Auckland Park, 2006, South Africa.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31701430

Citation

Wellington, Kevin W., et al. "Anticancer Activities of Vitamin K3 Analogues." Investigational New Drugs, 2019.
Wellington KW, Hlatshwayo V, Kolesnikova NI, et al. Anticancer activities of vitamin K3 analogues. Invest New Drugs. 2019.
Wellington, K. W., Hlatshwayo, V., Kolesnikova, N. I., Saha, S. T., Kaur, M., & Motadi, L. R. (2019). Anticancer activities of vitamin K3 analogues. Investigational New Drugs, doi:10.1007/s10637-019-00855-8.
Wellington KW, et al. Anticancer Activities of Vitamin K3 Analogues. Invest New Drugs. 2019 Nov 7; PubMed PMID: 31701430.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anticancer activities of vitamin K3 analogues. AU - Wellington,Kevin W, AU - Hlatshwayo,Vincent, AU - Kolesnikova,Natasha I, AU - Saha,Sourav Taru, AU - Kaur,Mandeep, AU - Motadi,Lesetja R, Y1 - 2019/11/07/ PY - 2019/04/30/received PY - 2019/09/11/accepted PY - 2019/11/9/entrez KW - 1,4-naphthohydroquinone KW - 1,4-naphthoquinone sulfides KW - Apoptosis KW - Cancer KW - Normal human fetal lung fibroblasts KW - Reactive oxygen species JF - Investigational new drugs JO - Invest New Drugs N2 - In a previous study we reported on the synthesis of 1,4-naphthoquinone-sulfides by thiolation of 1,4-naphthohydroquinones with primary aryl and alkyl thiols using laccase as catalyst. These compounds were synthesized as Vitamin K3 analogues. Vitamin K3 (VK3; 2-methyl-1,4-naphthoquinone; menadione) is known to have potent anticancer activity. This investigation reports on the anticancer activity of these VK3 analogues against TK10 renal, UACC62 melanoma, MCF7 breast, HeLa cervical, PC3 prostate and HepG2 liver cancer cell lines to evaluate their cytostatic effects. A 1,4-naphthohydroquinone derivative exhibited potent cytostatic effects (GI50 = 1.66-6.75 μM) which were better than that of etoposide and parthenolide against several of the cancer cell lines. This compound produces reactive oxygen species and disrupts the mitochondrial membrane potential in the MCF7 breast cancer cell line which is an indication that the cells undergo apoptosis. The 1,4-naphthoquinone sulfides also had potent cytostatic effects (GI50 = 2.82-9.79 μM) which were also better than that of etoposide, parthenolide and VK3 against several of the cancer cell lines. These compounds are generally more selective for cancer cells than for normal human lung fetal fibroblasts (WI-38). They also have moderate to weak cytostatic effects compared to etoposide, parthenolide and VK3 which have potent cytostatic effects against WI-38. One analogue induces apoptosis by activating caspases without arresting the cell cycle in the MCF7 breast cancer cell line. These results inspire further research for possible application in cancer chemotherapy. SN - 1573-0646 UR - https://www.unboundmedicine.com/medline/citation/31701430/Anticancer_activities_of_vitamin_K3_analogues L2 - https://doi.org/10.1007/s10637-019-00855-8 DB - PRIME DP - Unbound Medicine ER -