6-Methoxy Podophyllotoxin Induces Apoptosis via Inhibition of TUBB3 and TOPIIA Gene Expressions in 5637 and K562 Cancer Cell Lines


Iman Sadeghi, M.Sc, 1Mehrdad Behmanesh, Ph.D, 1,*Najmeh Ahmadian Chashmi, Ph.D, 2Mohsen Sharifi, Ph.D, 2Bahram Mohammad Soltani, Ph.D, 1
Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
Department of Plant Biology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
Department of Plant Biology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
*Corresponding Address: P.O.Box: 14115-154 Department of Genetics Faculty of Biological Sciences Tarbiat Modares University Tehran Iran Email:behmanesh@modares.ac.ir
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Abstract

Objective

Podophyllotoxin (PTOX), a natural compound in numerous plants, contains remarkable biological properties that include anti-tumor, anti-viral such as anti-human im- munodeficiency virus (HIV) activities. In order to avoid its adverse effects, various com- pounds have been derived from PTOX. 6-methoxy PTOX (MPTOX) is one of the natural PTOX derivatives with an extra methoxy group. MPTOX is mostly isolated from the Linum species. This study has sought to determine the biological effects of MPTOX on cancer cell lines, 5637 and K562.

Materials and Methods

In this experimental study, we treated the 5637 and K562 cancer cell lines with MPTOX in a doseand time-dependent manner. Apoptosis was examined by flow cytometry and viability rate was analyzed by the MTT assay. Expressions of the tubulin (TUBB3) and topoisomerase II (TOPIIA) genes were determined by real-time poly- merase chain reaction (PCR).

Results

Treatment with MPTOX led to significant induction of apoptosis in cancer cells compared to control cells. Gene expression analysis showed reduced levels of TUBB3 and TOPIIA mRNA following MPTOX treatment.

Conclusion

MPTOX inhibited TUBB3 and TOPIIA gene expression and subsequently induced cell death through apoptosis. These results suggested that MPTOX could be considered a potential anti-tumor agent.