Combination Effects of Docetaxel and Doxorubicin in Hormone-Refractory Prostate Cancer Cells

Abstract

Combination effects of docetaxel (DOC) and doxorubicin (DOX) were investigated in prostate cancer cells (PC3 and DU145). Combination indices (CIs) were determined using the unified theory in various concentrations and mixing ratios (synergy: CI < 0.9, additivity: 0.9 < CI < 1.1, and antagonism: CI > 1.1). DOC showed a biphasic cytotoxicity pattern with the half maximal inhibitory concentration (IC50) at the picomolar range for PC3 (0.598 nM) and DU145 (0.469 nM), following 72 h drug exposure. The IC50s of DOX were 908 nM and 343 nM for PC3 and DU145, respectively. Strong synergy was seen when PC3 was treated with DOC at concentrations lower than its IC50 values (0.125~0.5 nM) plus DOX (2~8 times IC50). Equipotent drug combination treatments (7 × 7) revealed that the DOC/DOX combination leads to high synergy and effective cell death only in a narrow concentration range in DU145. This study provides a convenient method to predict multiple drug combination effects by the estimated CI values as well as cell viability data. The proposed DOC/DOX mixing ratios can be used to design combination drug cocktails or delivery systems to improve chemotherapy for cancer patients.

In vivo evaluation of cetuximab-conjugated poly(&gamma;-glutamic acid)-docetaxel nanomedicines in EGFR-overexpressing gastric cancer xenografts

“…Altogether, the results from MTT assays, cell cycle analysis, mitochondrial membrane potential analysis and apoptosis analysis provide strong support to the idea that CET MAb conjugation could improve the therapeutic potential of Nps for EGFR +ve cancers. [52][53][54][55] …”

Anticancer Properties of Teucrium persicum in PC-3 Prostate Cancer Cells

“…When we compared the cytotoxic activity of Teucrium persicum with that of some known anti-cancer drugs, we found that the IC 50 value of Teucrium persicum extract for PC-3 cells was much lower. The IC 50 values reported for doxorubicin, imatinib and etoposide against PC-3 cells are 500, 5700 and 1730 μg/ml respectively (Kubler et al, 2005;Dudley et al, 2008;Tsakalozou et al, 2012) which are much higher than that of Teucrium persicum extract (142μg/ml).…”

Quinoline based mono- and bis-(thio)carbohydrazones: synthesis, anticancer activity in 2D and 3D cancer and cancer stem cell models

“…58,59 Hermandez-Vargas et al 59 were following changes in cell death, cell cycle, and gene transcription in MCF-7 and MDA-MB-231 breast cancer cell lines aer treatment with docetaxel. Their results revealed that docetaxel targeted different phases of cell cycle according to drug concentration, whereas a biphasic growth-response curve was in consistence with the existence of at least two different mechanisms of docetaxel's activity.…”

“…Later on, another group of authors concluded that biphasic doseresponse gained aer treatment of prostate cancer cell lines with docetaxel was occurred due to mitotic catastrophe at low concentrations, while apoptosis was the cause of cell death at concentrations higher than 10 mM. 58 Additionally, Szomolay and Shahrezaei 55 proposed a model where alterations in phosphorylation-dephosphorylation cycles due to different speeds of phosphatase and kinase activity can result in a variety of doseresponse behaviors.…”