Growth inhibitory effects of Phyllanthus niruri extracts in combination with cisplatin on cancer cell lines.
OBJECTIVE
To investigate the cytotoxic effects of spray-dried extracts of Phyllanthus niruri in combination with cisplatin on two cancer cell lines.


METHODS
Colorectal carcinoma (HT29) and human hepatocellular carcinoma (HepG2) cells were treated with spray-dried extracts of Phyllanthus niruri (SDEPN) either alone or in combination with cisplatin at different concentrations (0.5 mg/mL and 1 mg/mL) for 4 h and 24 h. To verify and quantify cancer cells treated with these products as well as identify the cell cycle stage and cell viability, we stained the cells with propidium iodide and assessed them by flow cytometry. The percentage of cells in different cell cycle phases was quantified and data were expressed as histograms. Significant differences between groups were determined using analysis of variance and Bonferroni's test, as indicated. A value of P < 0.05 was considered to be statistically significant.


RESULTS
SDEPN had significantly different cytotoxic effects on HT29 (2.81 ± 0.11 vs 3.51 ± 1.13, P > 0.05) and HepG2 (5.07 ± 0.3 vs 15.9 ± 1.04, P < 0.001) cells when compared to control cells for 4 h. SDEPN also had significantly different cytotoxic effects on HT29 (1.91 ± 0.57 vs 4.53 ± 1.22, P > 0.05) and HepG2 (14.56 ± 1.6 vs 35.67 ± 3.94, P < 0.001) cells when compared to control cells for 24 h. Both cell lines were killed by cisplatin in a dose-dependent manner compared to control cells (HepG2 cells for 4 h: 10.78 ± 1.58 vs 53.89 ± 1.53, P < 0.001; 24 h: 8.9 ± 1.43 vs 62.78 ± 1.87, P < 0.001 and HT29 cells for 4 h: 9.52 ± 0.913 vs 49.86 ± 2.89, P < 0.001; 24 h: 11.78 ± 1.05 vs 53.34 ± 2.65, P < 0.001). In HT29 cells, pretreatment with SDEPN and subsequent treatment with cisplatin resulted in a greater number of cells being killed (12.78 ± 1.01 vs 93.76 ± 1.6, P < 0.001). HepG2 cells showed significant cell killing with treatment with SDEPN when combined with cisplatin (12.87 ± 2.78 vs 78.8 ± 3.02, P < 0.001).


CONCLUSIONS
SDEPN is selectively toxic against two cancer cell lines. Moreover, SDEPN in combination with cisplatin induces a synergistic increase in the cell death of both HT29 and HepG2 cells.
Department of Morphology/Postgraduate Program in Morphological Sciences, Federal University of Rio Grande do Norte, Natal 59072-970, Rio Grande do Norte, Brazil.
Raimundo Fernandes
RF
Araújo
Luiz Alberto Lira
LA
Soares
Cínthia Raquel
CR
da Costa Porto
Ranniere Gurgel Furtado
RG
de Aquino
Hugo Gonçalo
HG
Guedes
Pedro Ros
PR
Petrovick
Tatiane Pereira
TP
de Souza
Aurigena Antunes
AA
Araújo
Gerlane Coelho Bernardo
GC
Guerra
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000473:pathology*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D066298:In Vitro Techniques; D008113:Liver Neoplasms / Q000473:pathology*; D029803:Phyllanthus; D010936:Plant Extracts / Q000494:pharmacology*
D000970:Antineoplastic Agents; D010936:Plant Extracts; D002945:Cisplatin