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Fig. 2 | Journal of Experimental & Clinical Cancer Research

Fig. 2

From: Synergistic antitumor interaction of valproic acid and simvastatin sensitizes prostate cancer to docetaxel by targeting CSCs compartment via YAP inhibition

Fig. 2

Mevalonic acid reverts the antiproliferative and apoptotic effect induced by valproic acid/simvastatin combination. a Overview of MVP and its principal inhibitors. b 22Rv1 cells untreated or treated for 72 h with VPA and/or SIM at the IC5096 h doses ± Mev (100 μM) to bypass the inhibition of HMGCR. Cell growth expressed as percentage of control was assessed by sulforhodamine B colorimetric assay. The values, expressed as percentage of control, are the means ± S.D. from at least three independent experiments. c Apoptosis was evaluated by Caspase 3/7 activity assay in 22Rv1 cells untreated or treated for 24 h with VPA and/or SIM at the IC5096 h doses ± Mev (100 μM). d Expression of cleaved PARP in 22Rv1 cell lines untreated or treated with VPA and/or SIM ± Mev (100 μM) for 24 h was evaluated by western blotting. γ-Tubulin was used as loading control. e 22Rv1 cells (40,000/mL) were seeded in sphere medium in low attachment 96 multiwell, to form 1st generation spheres (spheres A), as indicated in Methods section, and treated with VPA and SIM at the IC5096 h doses ± Mev (100 μM) for 72 h. Spheroids viability was assessed by luminescence assay. The values are the means ± S.D. from at least three independent experiments. Right: images from a representative experiment; left: values are the mean ± S.D. from at least three independent experiments. f 22Rv1 cells were seeded to form spheres D: cell seeded to form 1st generation spheres and concomitantly untreated or treated with VPA and /or SIM at the IC5096 h doses ± Mev (100 μM) for 72 h, then disaggregated and plated again to form 2nd generation spheres without additional treatment for 72 h, and the spheroids were manually counted (left: values are the means ± S. D from at least three independent experiments). g Cholesterol content was measured by NMR spectroscopy in untreated or 22Rv1-treated as indicated at the IC5096 h doses. The box and whisker plots summarize the normalized values of the proton signals of the cholesterol at 0.66 ppm for all samples. Statistically significant results are reported (*** indicates P < 0.0005, ** indicates P < 0.005 and * indicates P < 0.05)

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