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Antitumor activity of a novel synthetic cationic peptide AIK: A preliminary observation
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Abstract:
Objective:To evaluate the antitumor activity of a novel synthetic cationic peptide designated as AIK, and to elucidate the underlying mechanism(s) in vitro and in vivo . Methods：In experiments in vitro , the optimal dosage and treatment duration for AIK to exert its maximal cell proliferation inhibitory activity were determined by MTS cell proliferation assays in human leukemia HL-60 cells. And then, the antitumor activity of AIK at the optimal dosage and for the optimal duration of treatment was assessed in ten tumor cell lines (i.e., 95C, 95D, HL-60, HeLa, B95-8, HO-8910PM, HO-8910, SMMC-7721, U2OS, A549) and one human normal liver cell line HL-7702. The effects of AIK on HeLa cell apoptosis and morphology were examined by flow cytometry and microscopy respectively. In experiments in vivo, mouse liver cancer H22 cells were transplanted into the armpits of male Kunming mice. Thirty-six mice that developed tumors of a similar size as confirmed 5 days after H22 cell transplantation were randomized to receive subcutaneously PBS (vehicle control), low dose AIK (8 mg/\[kg?d\]), high dose AIK (15 mg/\[kg?d\]) and methotrexate (1 mg/\[kg?d\]) of as a positive control daily for 10 days, during which body weight was measured every day. Animals were sacrificed 24 h after the last treatment. Subcutaneous tumors were counted in each animal. Data on the weight and volume of the individual tumors were obtained and analyzed. Results： In vitro, AIK exhibited a potent cytotoxic activity against all types of cancer cells tested, in particular, the pulmonary giant cell carcinoma 95C cells, the leukemia HL-60 cells, and the cervical cancer HeLa cells. AIK treatment, as compared with vehicle control, resulted in significant increases in apoptosis (\[ 4.88± 0.57\]% vs \[0.51±0.19\]%, P <0.05) and necrosis (\[2.96±0.50\]% vs \[1.87±0.27\]%, P <0.05) in HeLa cells. Microscopic assessment showed necrotic phenomena including dilated, fragmented cell membrane and cell lysis in more than 50% of AIK treated H22 cells. In vivo, tumor volume and weight were significantly smaller in both AIK-and methotrexate-treated animals than in PBS-treated animals ( P <0.01). Body weight declined in methotrexate-treated animals but tended to increase in other 3 groups of animals 5 days after treatment. Nevertheless, the overall differences in body weight changes between the 4 groups of animals failed to reach a statistical significance ( P >0.05). Conclusion: The novel cationic peptide AIK possesses a potent antitumor activity both in vitro and in vivo , thus having a great therapeutic potential for various types of cancer.
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Project Supported:
Project supported by the National Natural Science Foundation of China (No.81272582)
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