ABSTRACT
Telmisartan, an angiotensin II receptor type 1 blocker, is often used as an antihypertension drug, and it has also been characterized as a peroxisome proliferator-activated receptor-gamma (PPARγ) ligand. The purpose of this study was to elucidate the antitumor effects of telmisartan on endometrial cancer cells. We treated three endometrial cancer cell lines with various concentrations of telmisartan, and we investigated the effects of the telmisartan on the cell proliferation, apoptosis, and their related measurements in vitro. We also administered telmisartan to nude mice with experimental tumors to determine its in vivo effects and toxicity. All three endometrial cancer cell lines were sensitive to the growth-inhibitory effect of telmisartan. The induction of apoptosis was confirmed in concert with the altered expression of genes and proteins related to the apoptosis. We also observed that DNA double-strand breaks (DSBs) were induced in HHUA (human endometrial cancer) cells by telmisartan treatment. In addition, experiments in nude mice showed that telmisartan significantly inhibited human endometrial tumor growth, without toxic side effects. Our results suggest that telmisartan might be a new therapeutic option for the treatment of endometrial cancers.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Benzimidazoles/pharmacology , Benzoates/pharmacology , DNA Breaks, Double-Stranded/drug effects , Endometrial Neoplasms/pathology , Animals , Cell Proliferation/drug effects , Cell Survival/drug effects , Endometrial Neoplasms/genetics , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Membrane Potential, Mitochondrial/drug effects , Mice , Telmisartan , Xenograft Model Antitumor AssaysABSTRACT
Cucurbitacin D, a newly isolated triterpenoid cucurbitacin, has been found to possess anticancer effects. The purpose of this study was to elucidate the effects of cucurbitacin D on human endometrial and ovarian cancer cells. Human endometrial and ovarian cancer cells were treated with various concentrations of cucurbitacin D, and its effects on cell growth, the cell cycle, apoptosis, and their related measurements were investigated in vitro. All endometrial and ovarian cancer cell lines were sensitive to the growth-inhibitory effect of cucurbitacin D. Cell cycle analysis indicated that their exposure to cucurbitacin D increased the proportion in the sub-G0/G1 phases and G2/M phases of the cell cycle. Induction of apoptosis was confirmed by annexin V staining of externalized phosphatidylserine and loss of the transmembrane potential of mitochondria. This induction occurred in concert with altered expression of genes related to cell growth, malignant phenotype, and apoptosis. Our results suggest that cucurbitacin D might be a new therapeutic option for the treatment of endometrial and ovarian cancers.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Cycle Checkpoints/drug effects , Endometrial Neoplasms/drug therapy , Ovarian Neoplasms/drug therapy , Triterpenes/pharmacology , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Endometrial Neoplasms/metabolism , Endometrial Neoplasms/pathology , Female , Humans , Membrane Potential, Mitochondrial/drug effects , Mitochondria/drug effects , Mitochondria/metabolism , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathologyABSTRACT
The potential anticancer agent 1-(2-chlorophenyl-N-methylpropyl)-3-isoquinolinecarboxamide (PK11195), a translocator protein ligand (initially described as a ligand for the peripheral benzodiazepine receptor), induces apoptosis in some lines of human tumor cells. We investigated the effect of PK11195 in the choriocarcinoma cell line, BeWo. BeWo cells were treated with various concentrations of PK11195, and changes in cell growth, the cell cycle, apoptosis, and related parameters were examined. A WST-1 assay showed that BeWo cells were sensitive to the growth inhibitory effect of PK11195. In contrast, the nonsite selective ligand diazepam has a little effect on these cells. Cell cycle analysis indicated that exposure to PK11195 decreased the proportion of cells in the S phase and increased the proportion in the G0/G1 phases of the cell cycle. Induction of apoptosis was confirmed by Annexin V staining of externalized phosphatidylserine, by the loss of mitochondrial transmembrane potential, and by antibodies directed against histones from fragmented DNA. This induction occurred in conjunction with the altered expression of genes related to cell growth, malignant phenotype, and apoptosis. These results suggest that PK11195 may serve as a therapeutic agent for the treatment of choriocarcinoma.
Subject(s)
Antineoplastic Agents/pharmacology , Hydatidiform Mole, Invasive/metabolism , Isoquinolines/pharmacology , Receptors, GABA/metabolism , Uterine Neoplasms/metabolism , Apoptosis/drug effects , Apoptosis Regulatory Proteins/genetics , Apoptosis Regulatory Proteins/metabolism , Caspase 3/metabolism , Caspase 7/metabolism , Cell Cycle/drug effects , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Enzyme Activation/drug effects , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Hydatidiform Mole, Invasive/genetics , Ligands , Membrane Potential, Mitochondrial/drug effects , Pregnancy , Uterine Neoplasms/geneticsABSTRACT
Bufalin is a traditional oriental medicines which induces apoptosis in some lines of human tumor cells. It constitutes the major digoxin-like immunoreactive component of Chan Su, obtained from the skin and parotid venom glands of toads. Bufalin is cardioactive C-24 steroids that exhibits a variety of biological activities, such as cardiotonic, anaesthetic, blood pressure stimulatory, respiratory and antineoplastic effects. In terms of its anti-tumor activity, bufalin has been demonstrated to inhibit the growth of tumors, such as endometrial and ovarian cancers. This commentary introduces biologic and therapeutic effects of bufalin in treating some cancers. The compound is able to mediate inhibition of cell growth, cell cycle arrest, apoptosis, and expression of genes related to the malignant phenotype in human cancer cells.
Subject(s)
Antineoplastic Agents/therapeutic use , Apoptosis/drug effects , Bufanolides/therapeutic use , Medicine, East Asian Traditional , Neoplasms/drug therapy , Neoplasms/pathology , Phytotherapy , Animals , Cell Cycle/drug effects , Cell Proliferation/drug effects , Clinical Trials as Topic , Drug Evaluation, Preclinical , Humans , Tumor Cells, CulturedABSTRACT
KN-93, a membrane-permeant calcium/calmodulin- dependent kinase-selective inhibitor, induces apoptosis in some lines of human tumor cells. We investigated the effect of KN-93 in the choriocarcinoma cell line, BeWo. BeWo cells were treated with various concentrations of KN-93, and changes in cell growth, the cell cycle, apoptosis, and related parameters were examined. A WST-1 assay showed that BeWo cells were sensitive to the growth inhibitory effect of KN-93. Cell cycle analysis indicated that exposure to KN-93 decreased the proportion of cells in the S phase and increased the proportion in the G0/G1 phases of the cell cycle. Induction of apoptosis was confirmed by Annexin V staining of externalized phosphatidylserine, by the loss of mitochondrial transmembrane potential, and by antibodies directed against histones from fragmented DNA. This induction occurred in conjunction with the altered expression of genes related to cell growth, malignant phenotype, and apoptosis. These results suggest that KN-93 may serve as a therapeutic agent for the treatment of choriocarcinoma.
