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Anticancer activities of vitamin K3 analogues

  • Kevin W. WellingtonEmail author
  • Vincent Hlatshwayo
  • Natasha I. Kolesnikova
  • Sourav Taru Saha
  • Mandeep Kaur
  • Lesetja R. Motadi
PRECLINICAL STUDIES

Summary

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.

Keywords

1,4-naphthoquinone sulfides 1,4-naphthohydroquinone Cancer Normal human fetal lung fibroblasts Reactive oxygen species Apoptosis 

Notes

Acknowledgements

We thank the CSIR (Thematic A grant) for financial support. The National Research Foundation Incentive Funding (No: 109163) and Claude Leon Foundation Merit Award (2016) to MK is also acknowledged.

Funding Information

This work was supported by the Biosciences unit, Council for Scientific and Industrial Research, Pretoria, South Africa.

Compliance with ethical standards

Conflict of interest

Kevin W. Wellington declares that he has no conflict of interest. Natasha I. Kolesnikova declares that she has no conflict of interest. Vincent Hlatshwayo declares that he has no conflict of interest. Sourav Taru Saha declares that he has no conflict of interest. Mandeep Kaur declares that she has no conflict of interest. Lesetja. R. Motadi declares that he has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

For this type of study, formal consent is not required.

Supplementary material

10637_2019_855_MOESM1_ESM.pdf (938 kb)
ESM 1 (PDF 937 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.CSIR BiosciencesPretoriaSouth Africa
  2. 2.Faculty of Health SciencesUniversity of the WitwatersrandJohannesburgSouth Africa
  3. 3.Centre for HIV and STI’sNational Institute for Communicable DiseasesJohannesburgSouth Africa
  4. 4.School of Molecular and Cell BiologyUniversity of the WitwatersrandJohannesburgSouth Africa
  5. 5.Department of BiochemistryUniversity of JohannesburgAuckland ParkSouth Africa

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