ABSTRACT
Objecive:To prove the molecular mechanisms of Mahkota Dewa (Phaleria macrocarpa) in suppressing proliferation of human retinoblastoma cells through suppression of cell cycle's gene-rcgulators expression.Methods:In this study,the molecular mechanism of anti-tumor effect of fractioned extract of Phaleria macrocarpa (DLBS1425) in human retinoblastoma cells Y-79 was investigated by measuring the tumor cells viability,the assessment of population profiles of tumor cells in the cell cycle,and the mRNA concentration of pi6,p21,p53,cyclin D,cyclin E,and E2F.Results:DLBS1425 showed an inhibition effects towards proliferation of Y-79 cell line.Inhibition of proliferation was shown by suppression of cell cycle progression.DLBS1425 downregulated cyclin E,a G1 phase regulator gene of cell cycle,in dosedependent manner without affecting p53-p21 pathway.In the other word,DLBS1425 inhibits cell proliferation through suppression of cyclin E independently towards conventional proliferation pathway.Conclusions:Our results suggest that DLBS 1425 is a potential anticancer agent which targets genes involved in cell proliferation in human retinoblastoma cells which make it pharmacologically ideal for the prevention and/or treatment of retinoblastoma cancer.
ABSTRACT
Objective To prove the molecular mechanisms of Mahkota Dewa (Phaleria macrocarpa) in suppressing proliferation of human retinoblastoma cells through suppression of cell cycle's gene-regulators expression. Methods In this study, the molecular mechanism of anti-tumor effect of fractioned extract of Phaleria macrocarpa (DLBS1425) in human retinoblastoma cells Y-79 was investigated by measuring the tumor cells viability, the assessment of population profiles of tumor cells in the cell cycle, and the mRNA concentration of p16, p21, p53, cyclin D, cyclin E, and E2F. Results DLBS1425 showed an inhibition effects towards proliferation of Y-79 cell line. Inhibition of proliferation was shown by suppression of cell cycle progression. DLBS1425 downregulated cyclin E, a G1 phase regulator gene of cell cycle, in dose-dependent manner without affecting p53–p21 pathway. In the other word, DLBS1425 inhibits cell proliferation through suppression of cyclin E independently towards conventional proliferation pathway. Conclusions Our results suggest that DLBS1425 is a potential anticancer agent which targets genes involved in cell proliferation in human retinoblastoma cells which make it pharmacologically ideal for the prevention and/or treatment of retinoblastoma cancer.
ABSTRACT
The objective of this study is to investigate the anticancer activity of 70 % ethanol extract of Mahkota dewa fruit pulp Phaleria macrocarpa (Scheff.) Boerl. using C3H mouse mammary tumor induced by transplantation. Thirty two C3H mice were devided into 4 groups i.e. control and 3 groups of mice treated with ethanol extract of Mahkota dewa fruit pulp with the dose of 20, 40, and 80 fold human dose respectively, given orally by gastric tube after tumor transplantation for 30 days. Body weight and tumor volume measured twice a week. Tumor weight was measured after the animal was sacrificed, then fixed in formaldehyde for making histopathological preparation. The proliferation activity of tumor cells were examined by counting the AgNOR deposits detected after colloidal AgNOR staining. Apoptosis was assessed by mean of Tunel staining, and the width of necrotic area was identified by hematoxyllin eosin staining of the histological specimen. The results of the study showed that there were no statistical differences in tumor volumes, tumor weights, AGNOR values, and the necrotic area among control and the three treated groups (p>0,05), but apoptosis index significantly increased in the D3 (Mahkota dewa extract of eighty fold human dose) group (p<0,05). It was concluded that ethanol extract of Mahkota dewa fruit pulp at the dose of 20,40, and 80 fold human dose given orally after tumor transplantation for 30 days, did not inhibit the C3H mouse mammary tumor growth induced by transplantation, but the increased apoptosis was found in the group receiving ethanol extract of Mahkota dewa fruit pulp at the dose of 80 fold human dose.