The cytotoxicity study of praziquantel enantiomers

Figures & data

Figure 1 rac-PZQ and its enantiomers.

Abbreviations: rac-PZQ, racemic praziquantel; PZQ, praziquantel.

Table 1 In vitro cytotoxicity of (R)-PZQ, (S)-PZQ, and rac-PZQ against eight cancer cell lines

Compounds	IC50 (μM)a
	L-02	HepG2	prf-plc-5	SH-SY5Y	HUVEC	A549	HCT-15	Raw264.7
rac-PZQ	106.0±2.0b	165.3±3.7	>200	>200	>200	>200	>200	>200
(R)-PZQ	>200**	64.2±1.8**	17.0±1.2**	>200	>200	>200	>200	>200
(S)-PZQ	80.4±1.9**	123.4±2.5*	>200	163.2±3.9	>200	>200	>200	>200

Notes:

a The cells were continuously treated with different concentrations (5 μM, 10 μM, 20 μM, 40 μM, 80 μM, 160 μM) of PZQ enantiomers for 48 hours; PZQ samples dissolved in DMSO. Cell viability was then determined by MTT assay.

b All data are expressed as means from three separate determinations. IC₅₀ values (mean ± SEM) were given only if they were <200 μM.

* P<0.05,

** P<0.01.

Abbreviations: rac, racemic; PZQ, praziquantel; DMSO, dimethyl sulfoxide; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; SEM, standard error of the mean.

Figure 2 The proliferation inhibition of (R)-PZQ, (S)-PZQ, and rac-PZQ assayed by MTT.

Notes: These eight cell lines were continuously treated with different concentrations (2.5 μM, 5 μM, 10 μM, 20 μM, 40 μM, 80 μM, 160 μM) of PZQ enantiomers for 48 hours. (A) L-02 cell line, (B) prf-plc-5 cell line, (C) HepG2 cell line, (D) SH-SY5Y cell line, (E) HUVEC cell line, (F) A549 cell line, (G) HCT-15 cell line, and (H) Raw264.7 cell line. Cell viability was then determined by MTT assay. P<0.05 at all compound concentrations.
Abbreviations: PZQ, praziquantel; rac, racemic; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide.

Figure 3 Fluorescent microscopic analysis of nuclei fragmentation by Hoechst 33342 staining.

Notes: Representative photomicrographs of four cell lines (L-02, HepG2, prf-plc-5, and SH-SY5Y) stained with Hoechst 33342 fluorescent dye after exposure to rac-PZQ, (R)-PZQ, and (S)-PZQ (drug concentrations were 0 μM and 160 μM) for 48 hours, respectively. The normal cells exhibited pale blue fluorescence and the apoptotic cells exhibited strong blue fluorescence. Magnification ×200, scale bars =50 μm. (A) Representative photomicrographs; (a) Control (0 μM); (b) rac-PZQ (160 μM); (c) (R)-PZQ (160 μM); and (d) (S)-PZQ (160 μM). (B) The cell viability quantified by hoechst 33342 staining. **P<0.01 in all treatment groups.
Abbreviations: PZQ, praziquantel; rac, racemic.

Figure 4 The cell viability rate of (R)-PZQ, (S)-PZQ, and rac-PZQ assayed by LDH.

Notes: These four cell lines (the results of other four cell lines are not shown) are continuously treated with different concentrations (2.5 μM, 5 μM, 10 μM, 20 μM, 40 μM, 80 μM, 160 μM) of PZQ enantiomers for 48 hours. (A) L-02 cell line, (B) prf-plc-5 cell line, (C) HepG2 cell line, and (D) SH-SY5Y cell line. Cell viability was then determined by LDH assay. P<0.05 at all concentrations.
Abbreviations: PZQ, praziquantel; rac, racemic; LDH, lactate dehydrogenase.