Marine-derived fungi extracts enhance the cytotoxic activity of doxorubicin in nonsmall cell lung cancer cells A459

Abstract

Background:Drug resistance is a major concern in the current chemotherapeutic approaches and the combination with natural compounds may enhance the cytotoxic effects of the anticancer drugs. Therefore, this study evaluated the cytotoxicity of crude ethyl extracts of six marine-derived fungi – Neosartorya tsunodae KUFC 9213 (E1), Neosartorya laciniosa KUFC 7896 (E2), Neosartorya fischeri KUFC 6344 (E3), Aspergillus similanensis KUFA 0013 (E4), Neosartorya paulistensis KUFC 7894 (E5), and Talaromyces trachyspermum KUFC 0021 (E6) – when combined with doxorubicin (Dox), in seven human cancer cell lines.Materials and Methods:The antiproliferative activity was primarily assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Results:Two extracts, E1 and E2, demonstrated a significant enhancement of Dox’s cytotoxicity in nonsmall cell lung cancer A549 cells. Accumulation of Dox in the nuclei increased when A549 cells were treated in combination with extracts E1 and E2, with induction of cell death observed by the nuclear condensation assay. The combination of E2 with Dox increased the DNA damage as detected by the comet assay. Ultrastructural observations by transmission electron microscopy suggest an autophagic cell death due to an increase of autophagic vesicles, namely with the combination of Dox with E1 and E2.Conclusion:These findings led to the conclusion that the fungal extracts E1 and E2 potentiate the anticancer action of Dox, through nuclear accumulation of Dox with induction of cell death mainly by cytotoxic autophagy.SUMMARYFungal extracts increase the cytotoxic activity of doxorubicin (Dox) in lung cancer cellsNuclear accumulation of Dox, DNA damage, and cell death as a mechanism of actionFungal extracts may potentiate the anticancer activity of conventional drugs.Abbreviations Used: A375: Human malignant melanoma cell line, A549: Human non small lung cancer cell line, DAPI: 4,6-Diamidino-2-phenylindole, DMEM: Dulbecco’s Modified Eagle Medium, DMSO: Dimethylsulfoxide, Dox: Doxorubicin, DSBs: DNA double-strand breaks, E1: Neosartorya tsunodae KUFC 9213, E2: Neosartorya laciniosa KUFC 7896, E3: Neosartorya fischeri KUFC 6344, E4: Aspergillus similanensis KUFA 0013, E5: Neosartorya paulistensis KUFC 7894, E6: Talaromyces trachyspermum KUFC 0021, FBS: Fetal bovine serum, HCT116: Human colorectal carcinoma cell line, HEPES: (N-[2-hydroxyethyl] piperazine-N’- [2-ethane-sulfonic acid]), HepG2: Human hepatocellular carcinoma cell line, HT29: Human Caucasian colon adenocarcinoma Grade II cell line, IC50: Concentration of the extract or Dox that inhibits cell viability by 50%, LRP: Lung resistance-related protein, MCF7: Human breast adenocarcinoma cell line, MEM: Minimum Essential Medium Eagle, MRPs: Multidrug resistance-associated proteins, MTT: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, PBS: Phosphate-buffered saline, NSCLC: Nonsmall cell lung cancer, P-gp: P-glycoprotein, ROS: Reactive oxygen species, RPMI: Roswell Park Memorial Institute Medium, TEM: Transmission elec...

Doxorubicin Loaded Thermosensitive Magneto-Liposomes Obtained by a Gel Hydration Technique: Characterization and In Vitro Magneto-Chemotherapeutic Effect Assessment

“…Cellular viability of A549 cells was measured by Alamar Blue (AB) and Neutral Red (NR) assays after exposure to various concentrations of DOX (ranging from 0.0145 to 0.870 µg/mL) for 24 and 48 h. The AB assay shows that the DOX presents a cytotoxic effect, after 24 h, starting with a concentration of 0.03 µg/mL. The cell viability decreases with increasing the DOX concentration, reaching a plateau of around 36% for the last three tested concentrations (Figure 3a) with an IC 50 of 0.3 µg/mL, similar to other reports in the literature for A459 cells [70]. By doubling the incubation time to 48 h, the cell viability continued to decrease for all concentrations (Figure 3b).…”

“…The SAR dependence of Zn ferrites on the concentration and amplitude of the magnetic field is presented in Figure 1g for the concentration range 0.25-4.00 mg Fe /mL. The SAR dependence on the amplitude of the alternating magnetic field is sigmoidal and was fitted with a logistic function (Equations (S3) and (S4)), to obtain the SAR max and the hyperthermia coercive field, i.e., the point of highest slope in the SAR = f(H max ) curve [70]. The concentration dependence of SAR is nonmonotonic.…”

Medicinal potential of mycelium and fruiting bodies of an arboreal mushroom Fomitopsis officinalis in therapy of lifestyle diseases

“…In this work, the extracts were investigated for antiproliferative activity against three commonly studied cell lines 34 – 36 . Previous studies showed that the cytotoxic properties of F. officinalis were mainly associated with the presence of lanostane saponins 37 , 38 .…”

Efficacy of Penicillium limosum Strain AK-7 Derived Bioactive Metabolites on Antimicrobial, Antioxidant, and Anticancer Activity against Human Ovarian Teratocarcinoma (PA-1) Cell Line

“…The results were similar to the earlier reports where Penicillium sclerotiorum extract treated A549, A431, U251, and HeLa cancer lines showed a significant reduction in cell viability and increased eventual cell death (apoptosis) at the IC 50 concentrations of 10, 20, 32 and 7.75 µg/mL [56]. Apoptosis can be instigated by the effective action of the drug, which causes DNA fragmentation, prevention of DNA replication, breaking of DNA double-strand (through inactivation of topoisomerase II), ROS generation (reactive oxygen species), affect the mitochondrial functioning level, and finally, damage of DNA which leads to the apoptosis [57][58][59][60]. In the present context, AK-7 extract significantly induced and influenced the apoptosis mechanism in the PA-1 cell line through a series of mechanisms that finally led to mitochondrial dysfunction and cell death compared to the untreated cell line.…”