Effects of Artesunate with Paclitaxel on the Proliferation and Morphology of Androgen‐sensitive (LNCaP), Androgen‐insensitive (PC‐3) Human Prostate Cancer Cell Lines and Normal Epithelial Prostate cell line (RWPE‐1)

Abstract

BackgroundProstate cancer is one of the diseases worldwide that causes cancer‐related deaths in men and is the second most common cancer affecting thousands of men each year in the United States behind only lung cancer. Artesunate (ART) is part of the artemisinin drugs for the treatment of malaria. Paclitaxel (PTX) is an anticancer agent that belongs to the Taxane class and is used for the treatment of metastatic hormone‐refractory prostate cancer.PurposeThe aim of this study was to examine the effects of combining ART with PTX on human prostate cancer cell lines ‐ LnCAP and PC‐3, normal epithelial prostate cell line RWPE‐1 and observe any morphological change using Scanning Electron Microscope (SEM).MethodIn vitro anti‐proliferative 3‐(4,5‐Dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium (MTS) assay was used to assess the effects of ART with PTX on human prostate cancer cell line (LnCaP and PC‐3) and normal prostate cell line (RWPE‐1) after 72‐ and 120 – hour exposure at a concentration range from 1 nm – 100 μM. For the SEM images, cell lines were cultured with thin films of gold, titanium and zinc oxide deposited by magnetron sputtering on silicon substrate at room temperature. Images of samples with and without the drugs were acquired.ResultsThe average cell death observed for both LnCAP and PC‐3 cell lines was 40% and 73% after 72‐ and 120‐ hours incubation with ART and PTX at different combination ratios of 1:1; 1:2 and 2:1 for ART: PTX and 1:1; 1:2 and 2:1 for PTX: ART with concentrations ranging from 1 nm – 100 μM. For normal epithelial prostate cell line, RWPE‐1, the average cell death observed ranged from 0.35% – 23% using the same combination ratios. Cell adhesion was detected on silicon substrates and on thin films of gold, titanium and zinc oxide. Morphological changes were observed when samples were treated with and without drugs. These SEM images were associated with cell lines undergoing apoptosis when compared with control (images with no drugs).ConclusionAlthough further observations are needed, it appeared that combination of ART with PTX displayed cytotoxicity regardless of whether the prostate cancer cell line is androgen‐sensitive or androgen‐insensitive after 72 and 120 ‐ hour exposure with little or no effect on normal epithelial prostate cell line. Therefore, combination of both drugs may aid in reducing cardio‐toxicity exerted by PTX alone thereby reducing the prostate cancer mortality rate in men.Support or Funding InformationWork support by ECSU Mini‐grant and in part by NSF Award# 1818774