Antitumor effect of a polypeptide fraction from Arca subcrenata in vitro and in vivo

Abstract

Arca subcrenata Lischke is a marine traditional Chinese medicine. The study investigated the antitumor effects of P2, a polypeptide fraction from A. subcrenata, and its toxicity in vitro and in vivo. The results showed that P2 could inhibit the proliferation of seven tumor cell lines, especially in HeLa and HT-29 cell lines. The IC₅₀ values were 11.43 μg/mL for HeLa and 13.00 μg/mL for HT-29 treated by P2 for 48 h. P2 had little cytotoxicity on normal liver cells (L-02). The maximum tolerated dose (MTD) of P2 on KM mice was 1000 mg/kg by i.p. or i.v. The tumor growth inhibitory ratios of P2 were 26.4%, 41.4% and 46.4% for H-22, and 34.0%, 45.8% and 60.1% for S-180 tumor-bearing mice. The results demonstrated that P2 might be a potential antitumor agent with high efficiency in dose-dependent and time-dependent manners and low toxicity.

Figure 1

Effects of P2 on cell viability of human tumor cell lines. Seven tumor cell lines were treated by P2 at different concentrations for 48 h. Cell viability was determined by MTT assay. Data are presented as mean ± SD of three independent experiments.

Figure 2

Selective cytotoxicity effects of P2 on HeLa and HT-29 cells compared with normal liver L-02 cells. Data are presented as mean ± SD of three independent experiments.

Figure 3

Cytotoxicity of P2 on HeLa (A) and HT-29 (B) cells in a dose- and time-dependent manner. The IC₅₀ was calculated according to the inhibition rate by Graph Pad software. Data are presented as mean ± SD of three independent experiments.

Figure 4

Cytotoxicity of P2 on cancer cells of HeLa and HT-29 and on normal liver L-02 cells.

Figure 5

Histopathologic analysis by H & E staining of five kinds of organs of P2-treated mice comparing with control mice (normal saline).

Figure 6

Antitumor effects of P2 against tumor growth on the S-180 (A) and H-22 (B) xenograft mice. Mice transplanted with S-180/H-22 cells were treated by P2 (7, 21, 63 mg/kg/day), CTX (25 mg/kg/day) or normal saline (10 mL/kg) for a consecutive nine days. Then the mice were sacrificed, and the tumors were excised. The images showed the tumor masses of mice treated by P2, CTX or normal saline.