Fern Plant–Derived Protoapigenone Leads to DNA Damage, Apoptosis, and G₂/M Arrest in Lung Cancer Cell Line H1299

Abstract

Protoapigenone, isolated from the native fern plant Thelypteris torresiana, has anticancer activity against some cancer cells. However, the toxicological mechanism for protoapigenone is still unknown. Here, we investigated the anticancer effect of protoapigenone on human lung cancer cell lines. The comet assay showed that DNA damage induced by protoapigenone is dose-dependent. Trypan blue exclusion showed that the cell killing by protoapigenone is both time and dose dependent. The IC(50) of protoapigenone for 12, 24, and 48 h in H1299 cells is 6.11, 2.74, and 1.49 microM, respectively. Flow cytometry showed cell cycle perturbation such as sub-G(1) accumulation (at 1.57 microM for 48 h and at 3.57 microM for 12 and 24 h) and G(2)/M arrest (at 3.57 microM for 12 and 24 h) for protoapigenone. The sub-G(1) accumulation phenomena in the 3.57 microM for 24 h sample were shown to be apoptosis using Annexin V-immunofluorescence/propidium iodide staining. These results suggest protoapigenone is a potential chemotherapeutic agent for lung cancers.

Inhibition of ATR-Dependent Signaling by Protoapigenone and Its Derivative Sensitizes Cancer Cells to Interstrand Cross-link–Generating Agents In Vitro and In Vivo

“…Previously, WYC02 and WYC0209 were shown to cause DNA strand breaks and apoptosis in lung and prostate cancers (18,20), suggesting that inducing DNA damage may be the potential mechanism underlying the anticancer effect of WYCs. To test this hypothesis, we investigated the cytogenetic effect of WYC02 on CHO cells (Fig.…”

“…1A) were shown to induce oxidative stress, consequently activating the p38 and c-jun-NH 2 -kinase (JNK) 1/2 mitogen-activated protein kinase (MAPK) pathways following cell-cycle arrest and apoptosis in several cancer cell types. These compounds were also found to reduce the size of tumor xenografts in nude mice without exerting toxic effects on the recipient (18)(19)(20)(21)(22). Recently, WYCs were found to induce chromosomal breakage through oxidative stress (18,20), implicating a role for WYCs in interfering with DNA metabolism.…”

“…These compounds were also found to reduce the size of tumor xenografts in nude mice without exerting toxic effects on the recipient (18)(19)(20)(21)(22). Recently, WYCs were found to induce chromosomal breakage through oxidative stress (18,20), implicating a role for WYCs in interfering with DNA metabolism. To date, the biomolecular actions and implications of this WYC-mediated interference are mostly undetermined.…”

A review of the use of pteridophytes for treating human ailments

“…4c) and P. multifida have cytotoxic effects due to the presence of diterpenes (Woerdenbag et al, 1996;Li et al, 1998Li et al, , 1999. Several authors have studied the anti-cancer potentials of ferns and lycopods, namely P. aquilinum, Davallia cylindrical, Stenoloma chusanum, Selaginella frondosa, Thelypteris torresiana, P. vittata, Selaginella ciliaris, Marsilea minuta, and Thelypteris prolifera (Chiu et al, 2009;Sarker et al, 2011;Tomsik, 2013;Zhang et al, 2013;Kaur et al, 2014;Xia et al, 2014).…”

Modulating Roles of Amiloride in Irradiation-Induced Antiproliferative Effects in Glioblastoma Multiforme Cells Involving Akt Phosphorylation and the Alternative Splicing of Apoptotic Genes

“…The trypan blue dye exclusion method (Chiu et al, 2009;Yen et al, 2010) was used to measure the viability of cells treated with 0.2 mM amiloride and/or 5 Gy ionizing radiation (IR) for the time intervals of 24, 48, and 72 h. Exponentially grown cells (1 · 10 4 ) were plated in 96-well plates until 90% confluence was achieved. The cells were then treated with 0.2% trypan blue and counted with a hemocytometer (SigmaAldrich).…”