Tian-Wei Zhang, Li Xing, Jun-Long Tang, Jing-Xiao Lu, Chun-Xiao Liu
Department of Urology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China (mainland)
Med Sci Monit 2015; 21:3570-3576
Apoptosis is mediated by the endoplasmic reticulum (ER) stress pathway, mitochondrial pathway, and death receptor. Data herein suggested an inhibitory effect of marchantin M on tumor formation in nude mice as well as the impact on CHOP and GRP78 expression.
MATERIAL AND METHODS: The role of marchantin M on proliferation and apoptosis of DU145 cells were measured by MTT and flow cytometry, respectively. Western blot was applied to detect the expression of GRP78 and CHOP. The mice received abdominal injection at 1 time/2 d and 2 ml/time. Tumor volume was measured every 6 days. The mice were euthanatized 30 days after marchantin injection and tumor weight was measured. Cell apoptosis was determined by TUNEL. The expressions of CHOP and GRP78 were detected by immunohistochemistry.
RESULTS: Tumor size and weight in marchantin groups were significantly lower than in the control group (A, B) (P<0.05), and the inhibitory rate presented a dose-dependent increase. Compared with controls, the levels of CHOP and GRP78 expression elevated obviously following the treatment with marchantin (P<0.05). It showed statistically significant difference among groups C, D, E, with different levels of apoptosis indexes incremented in groups of marchantin H, M, L, compared with groups A and B (P<0.05).
CONCLUSIONS: Overall, this study shows that marchantin M circumvents the growth of prostate cancer PC-3 tumor and up-regulates expressions of CHOP and GRP78. Our data also indicate that marchantin M limits the proliferation and favors apoptosis of DU145 cells in a time- and dose-dependent manner.
Keywords: Antineoplastic Agents - pharmacology, Animals, Apoptosis - drug effects, Bibenzyls - pharmacology, Cell Line, Tumor, Endoplasmic Reticulum Stress - drug effects, Heat-Shock Proteins - metabolism, In Situ Nick-End Labeling, Mice, Mice, Nude, Mitochondria - genetics, Phenyl Ethers - pharmacology, Prostatic Neoplasms - pathology, Transcription Factor CHOP - metabolism, Up-Regulation