title: Alpha-momorcharin (α-MMC) exerts effective anti-human breast tumor activities but has a narrow therapeutic window in vivo.
abstract: Alpha-momorcharin (α-MMC), a ribosome inactivating protein (RIP) extracted from the seeds of Momordica charantia, exerts anti-tumor, antiviral, and anti-fungal activities. However, α-MMC has an obvious toxicity that limits its clinical application. We examined the effect of α-MMC on the inhibition of human breast cancer and assessed its general toxicity to find the therapeutic window in vivo for its potential clinical use. It was purified using column chromatography, and then injected into the xenograft nude mouse model induced by MDA-MB-231 and MCF-7. The anti-tumor efficacy was evaluated with T/C%. Next, the α-MMC was injected at a series of doses to Balb/C mice to assess its general toxicity. The MTT assay, the apoptosis test, and the cell cycle inhibition of α-MMC in human breast cancer cells were performed. In the xenografted tumors induced by MDA-MB-231 and MCF-7, α-MMC exerted an obvious inhibition effects on tumor growth at the dosage of 1.2mg/kg and 0.8 mg/kg. For in vivo toxicity experiments of α-MMC in Balb/C mice, the minimal toxic dose of α-MMC was 1.2mg/kg. Alpha-MMC induced apoptosis by increasing caspase3 activities, and the cell cycle was arrested at the G0/G1 or G2/M phases. The measurements of IC50 were 15.07 μg/mL, 33.66 μg/mL, 42.94 μg/mL for MDA-MB-231, MCF-7 and MDA-MB-453 respectively. Alpha-MMC exhibits anti-tumor effects in human breast cancer in vivo and in vitro. It inhibits breast cancer cells through the inhibition of tumor growth and induction of cell apoptosis. However, due to its obvious toxicity, α-MMC has a relatively narrow therapeutic window in vivo.
authors.affiliation: School of Medical Laboratory Science, Chengdu Medical College, Chengdu 610500, PR China.
authors.forename: Dongliang
authors.initials: D
authors.lastname: Cao
authors.affiliation: Department of Gastroenterology, The First Attached Hospital of Chengdu Medical College, Chengdu Medical College, Chengdu 610500, PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Sun
authors.affiliation: School of Medical Laboratory Science, Chengdu Medical College, Chengdu 610500, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Qianchuan
authors.initials: Q
authors.lastname: He
authors.affiliation: School of Medical Laboratory Science, Chengdu Medical College, Chengdu 610500, PR China.
authors.forename: Juecun
authors.initials: J
authors.lastname: Zheng
authors.affiliation: School of Medical Laboratory Science, Chengdu Medical College, Chengdu 610500, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Deng
authors.affiliation: School of Medical Laboratory Science, Chengdu Medical College, Chengdu 610500, PR China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Deng
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: ShuChing
authors.initials: S
authors.lastname: Chang
authors.affiliation: Center of Science and Research, Chengdu Medical College, Chengdu 610083, PR China.
authors.forename: XiaoPing
authors.initials: X
authors.lastname: Yu
authors.affiliation: Center of Science and Research, Chengdu Medical College, Chengdu 610083, PR China.
authors.forename: Minhui
authors.initials: M
authors.lastname: Li
authors.affiliation: School of Medical Laboratory Science, Chengdu Medical College, Chengdu 610500, PR China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Meng
authors.affiliation: School of Medical Laboratory Science, Chengdu Medical College, Chengdu 610500, PR China.
authors.forename: Jiagui
authors.initials: J
authors.lastname: Jin
authors.affiliation: School of Medical Laboratory Science, Chengdu Medical College, Chengdu 610500, PR China. Electronic address: shenfubing@163.com.
authors.forename: Fubing
authors.initials: F
authors.lastname: Shen
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D029777:Momordica charantia / Q000737:chemistry; D054788:Ribosome Inactivating Proteins / Q000494:pharmacology* / Q000633:toxicity; D012639:Seeds / Q000737:chemistry; D018675:Toxicity Tests; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C039582:MMC protein, Momordica charantia; D054788:Ribosome Inactivating Proteins
keywords: Alpha-momorcharin; Apoptosis; Human breast tumor; Ribosome inactivating protein; Therapeutic window