RESUMO
Prostate cancer is the third leading cause of cancer death among men worldwide and is the leading cause of cancer mortality in males greater than 60 years in Trinidad and Tobago. Although there are some treatment options for the metastatic disease, the impact on overall survival rate has not improved in the last two decades. In particular, the mortality rate from prostate cancer is high among men of African descent in Trinidad and Tobago and the Americas. These groups manifest aggressive cancers that are often less responsive to available therapies. We hypothesize that phytochemical screening of tropical plants, coupled to cell culture studies would identify other potential treatments for prostate cancer. In separate experiments, the roots or leaves of five plants indigenous to the Caribbean and the skin of the muscadine grape, indigenous to North America were dried, crushed and suspended in 100% methanol. The respective methanol extracts were fractionated and the fractions dried. Next the ability of the extracts to halt the growth of or kill PC-3 prostate cancer cells was assessed by MTT assays. Colony formation, cell migration studies, cell cycle studies and western blots were performed to determine probable mechanism of action. The categories of chemical compounds present in the extracts were determined by Thin Layer chromatography (TLC). Results from MTT assays showed that compared to the control cells (ie those treated with DMSO only), treatment with at least four plant extracts significantly (p<0.05) inhibited the growth of the cancer cells; decreases as large as 95 % were observed. On the other hand these extracts had a limited or delayed effect on the "normal" PNT1A cells. Results from the cell cycle assay demonstrated that one extract, now identified as plant-A extract, caused the arrest of the G1/S phase of PC-3 cells i.e. leading to an increase in the number of cells that remained in the growth phase. On the other hand the total ethanol extract of muscadine grape skin decreased the expression of heat shock protein-40, possibly causing deactivation of the androgen receptor. This suggests that extracts prepared from Plant A and the muscadine grape have the potential for use as anticancer drugs.
Assuntos
Humanos , Masculino , Neoplasias da Próstata , Trinidad e TobagoRESUMO
Prostate cancer is the third leading cause of cancer death among men worldwide and is the leading cause of cancer mortality in males greater than 60 years in Trinidad and Tobago. Although there are some treatment options for the metastatic disease, the impact on overall survival rate has not improved in the last two decades. In particular, the mortality rate from prostate cancer is high among men of African descent in Trinidad and Tobago and the Americas. These groups manifest aggressive cancers that are often less responsive to available therapies. We hypothesize that phytochemical screening of tropical plants, coupled to cell culture studies would identify other potential treatments for prostate cancer. In separate experiments, the roots or leaves of five plants indigenous to the Caribbean and the skin of the muscadine grape, indigenous to North America were dried, crushed and suspended in 100% methanol. The respective methanol extracts were fractionated and the fractions dried. Next the ability of the extracts to halt the growth of or kill PC-3 prostate cancer cells was assessed by MTT assays. Colony formation, cell migration studies, cell cycle studies and western blots were performed to determine probable mechanism of action. The categories of chemical compounds present in the extracts were determined by Thin Layer chromatography (TLC). Results from MTT assays showed that compared to the control cells (ie those treated with DMSO only), treatment with at least four plant extracts significantly (p<0.05) inhibited the growth of the cancer cells; decreases as large as 95 % were observed. On the other hand these extracts had a limited or delayed effect on the "normal" PNT1A cells. Results from the cell cycle assay demonstrated that one extract, now identified as plant-A extract, caused the arrest of the G1/S phase of PC-3 cells i.e. leading to an increase in the number of cells that remained in the growth phase. On the other hand the total ethanol extract of muscadine grape skin decreased the expression of heat shock protein-40, possibly causing deactivation of the androgen receptor. This suggests that extracts prepared from Plant A and the muscadine grape have the potential for use as anticancer drugs.