Effect of active compounds isolated from Pteris semipinnata L on DNA topoisomerases and tyrosine protein kinase and expression of C-MYC in lung adenocarcinoma cells

Abstract

Objective: To study the effect of active compound 6F and A from Pteris semipinnata L.(PsL) on the activities of DNA topoisomerase (TOPO) I and lI, activities of cytosolic and membrane TPK, and expression of oncogene c-myc in lung adenocarcinoma cells. Methods: The effect of compound 6F and A on activities of cytosolic and membrane TPK was measured by scintillation counting; the effect of compound A on expression of oncogene c-myc was determined by flow cytometry indirect fluorimetry. Results: compound 6F and A could inhibit the activities of TOPO I, and they strongly inhibited the TOPO II in 0.01 mg/L and 10.0 mg/L respectively. Compound A slightly inhibited the activities of membrane TPK, but not the cytosolic one. Compound A could inhibit the expression of oncogene c-myc. Conclusion: Topoisomerases are target of compound 6F and A. Compound A could slightly inhibit the activities of TPK, and showed an inhibitory effect on the expression of oncogene c-myc. Tyrosine protein kinase, c-mycTopoisomerases are key nuclear enzymes, which play critical role during cell growth. They alter DNA topology and adjust the conformation of DNA molecules by strand breakage and rejoining. Two types have been identified, topoisomerase I (TOPO I) and topoisomerase II (TOPO II). TOPO I breaks the single DNA strands by trapping the enzyme in an incovalent bond form with its DNA substrate, and it is an ATP-independent enzyme. TOPO II affect DNA replication through inducing a transient breakage of single or double DNA strands and then rejoining the strand break, it needs ATP to provide energy in the reaction catalyzed r11. It was reported that most of the TOPO I and/or TOPO II inhibitors were important clinically used antineoplastic agents, such as camptothecin(CPT), doxorubicin, etoposide (Vp-16), and 4'-[9-acridinylamino]-N-[methane-sulfonyl]-m-anisidine] (m-AMSA) ~241. They catalyze single or double DNA breakage by intercalating or nonintercalating to DNA, and then interfere with the function of enzymes. Tyrosine protein kinase (TPK) is a kinase which phosphorylates the tyrosine residue in protein. It was proved that TPK was associated with cell proliferation, differentiation, oncogene activation, and signal transduction Es6~. Both of TOPOI and TOPO II are TPK's substrates in vitro. Some compounds which were considered as specific TPK inhibitors were also TOPOI and/or TOPO II inhibitors.Pteris semipinnata L (PsL) is a Chinese traditional herb. Its extract showed obvious antitumor activity in vivo and in vitro t71. We preciously reported various compounds isolated from PsL could inhibit the growth of several human tumor cell lines in vitro E81. In this paper, we report the effects of active

Phytochemicals from fern species: potential for medicine applications

“…In addition to ent-11α-hydroxy-15-oxo-kaur-16en-19-oic-acid, 7,9-dihydroxy-15-oxo-ent-kaur-16en-19,6-olide and 7,11-dihydroxy-15-oxo-ent-kaur-16-en-19,6-olide from P. semipinnata can inhibit lung adenocarcinoma cells by acting as inhibitors of DNA topoisomerases (TOPO) and tyrosine protein kinase (TPK) (Tomšík 2014). 7,9-Dihydroxy-15-oxoent-kaur-16-en-19,6-olide inhibited TOPO II at a concentration of 0.01 mg/L, while 7,11-dihydroxy-15-oxo-ent-kaur-16-en-19,6-olide was a moderately potent inhibitor of membrane TPK and also reduced the expression of the oncogene c-myc (Li et al 2001).…”

Over-expression of Bcl-2 against Pteris semipinnata L-induced apoptosis of human colon cancer cells via a NF-kappa B—related pathway

“…Pteris semipinnata L (PsL) is a Chinese traditional herb, which has been used to treat variety of inflammatory conditions such as hepatitis, enteritis and snake bite. 1 Recently, several chemical compounds have been identified from the ethanolic extract of the PsL. Some of these compounds are able to inhibit the growth of tumor cells, including gastric adenocarcinoma cells (MGC-803), lung adenocarcinoma cells (SPC-A-1), human promyelocytic leukemia cells (HL-60), nasopharyngeal carcinoma cells (CNE-2Z), and liver adenocarcinoma cells (BEL-7402, HepG2).…”

Potencial alelopático de espécies de Pteridaceae (Pteridophyta)

“…Li et al (1999) isolaram compostos com propriedades antitumorais a partir de P. semipinnata L. Não foram encontrados relatos na literatura tratando de estudos químicos ou biológicos com P. denticulata, que foi objeto de avaliação quanto à atividade alelopática, no presente estudo.…”