Suppressive effects of swainsonine on C6 glioma cell in vitro and in vivo.
Swainsonine, an extract from Astragalus membranaceus, is known for its anti-cancer effects and could prevent metastases. In order to investigate the effects and mechanisms of swainsonine in C6 glioma cells, we carry out correlated experiments in vitro and in vivo. After treatment with swainsonine, the effective dose and IC(50) value of swainsonine in the C6 glioma cell were examined using the MTT assay. Cell cycle distribution and apoptotic rates were analyzed using FCM and [Ca(2+)](i) was measured by LSCM. Expressions of p16 and p53 protein were evaluated by immunocytochemical methods. Simultaneously, glioma-bearing rats were administered swainsonine at doses of 2, 4 and 8 mg/kg body wt. The inhibition rate was calculated and pathological sections were observed. The results indicated that the growth of C6 glioma cells is inhibited by swainsonine in vitro, with an IC(50) value within 24h of 0.05 microg/ml. Increases in swainsonine correlate with S phase percentages of 11.3%, 11.6% and 12.4%, respectively. Moreover, the expression of apoptosis inhibiting p53 and p16 protein decreases gradually. Tumor weight in vivo decreased clearly and HE dyeing of tumor tissue showed gray, its texture was soft, with necrosis and hemorrhagic concentrated inward. Swainsonine could inhibit the proliferation of C6 glioma cells in vitro and the growth of C6 glioma in vivo. The mechanisms of swainsonine-induced apoptosis may relate with the expression of apoptosis-related genes and overloading-[Ca(2+)](i)-induced endoplasmic reticulum stress.
Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi'an, PR China.
Ji-Yuan
JY
Sun
Hao
H
Yang
Shan
S
Miao
Ji-Peng
JP
Li
Si-Wang
SW
Wang
Miao-Zhang
MZ
Zhu
Yan-Hua
YH
Xie
Jian-Bo
JB
Wang
Zhe
Z
Liu
Qian
Q
Yang
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D027883:Astragalus Plant; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D019942:Genes, p16 / Q000187:drug effects; D016158:Genes, p53 / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D017026:Swainsonine / Q000494:pharmacology* / Q000627:therapeutic use
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D017026:Swainsonine; D002118:Calcium