title: Inhibition on the growth of human MDA-MB-231 breast cancer cells in vitro and tumor growth in a mouse xenograft model by Se-containing polysaccharides from Pyracantha fortuneana.
abstract: Breast cancer is the second cause of cancer-related death among Women. Current therapies for breast cancer have adverse side-effects. Selenium (Se)-containing polysaccharides have multiple health benefits to humans. Pyracantha fortuneana (P. fortuneana) contains rich Se polysaccharides. We hypothesized that Se-containing polysaccharides from P. fortuneana possess anticancer activity on breast cancer via inhibiting growth and inducing apoptosis. This study aimed to assess the anticancer effect of Se-containing polysaccharides from P. fortuneana and the underlying mechanisms. Se-containing polysaccharides were purified. Their properties and monosaccharide compositions were analyzed. Their effects on cell growth, expression of cycle proteins, apoptosis and apoptosis-related protein, and tumor growth in mouse xenograft model were examined. This extract contained 93.7% (w/w) of carbohydrate, 2.1% (w/w) of uronic acid and 3.7μg/g of Se, and was considered as Se-conjugated polysaccharides (Se-PFPs). In vitro studies showed that treatment of triple negative breast cancer (TNBC) MDA-MB-231 cells with Se-PFPs (1) inhibited cell growth dose-dependently by arresting cells at G2 phase via inhibiting CDC25C-CyclinB1/CDC2 pathway; (2) caused apoptosis associated with increased p53, Bax, Puma and Noxa, decreased Bcl2, increased Bax/Bcl2 ratio and increased activities of caspases 3/9, suggesting its effect on p53-mediated cytochrome c-caspase pathway. Treatment of nude mice bearing MDA-MB-231-derived xenograft tumors with Se-PFPs significantly reduced tumor growth without altering body weight, confirming its antitumor activity without toxic side effects. Se-PFPs enhanced doxorubicin cytotoxic effects. It is concluded that Se-containing polysaccharides from P. fortuneana potently inhibit the growth and induce apoptosis of TNBC cells and can be potential anticancer agent for TNBC.
authors.affiliation: College of Medical Science, China Three Gorges University, Yichang, HuBei 443002, China; Renhe Hospital, China Three Gorges University, Yichang, HuBei 443002, China. Electronic address: yuancf46@ctgu.edu.cn.
authors.forename: Chengfu
authors.initials: C
authors.lastname: Yuan
authors.affiliation: Molecular Medicine & Cancer Research Center, Chongqing Medical University, Chong qing 400016, China.
authors.forename: Changdong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Renhe Hospital, China Three Gorges University, Yichang, HuBei 443002, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom Institute of Agriculture, Technology & Sciences, Allahabad, Uttar Pradesh 211007, India.
authors.forename: Vikas
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Department of Biochemistry, Faculty of Science, King Abdulaziz University, P.O. Box: 80200, Jeddah 21589, Saudi Arabia.
authors.forename: Firoz
authors.initials: F
authors.lastname: Anwar
authors.affiliation: College of Medical Science, China Three Gorges University, Yichang, HuBei 443002, China.
authors.forename: Fangxiang
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Department of Biochemistry, Faculty of Science, King Abdulaziz University, P.O. Box: 80200, Jeddah 21589, Saudi Arabia.
authors.forename: Gohar
authors.initials: G
authors.lastname: Mushtaq
authors.affiliation: Department of Pathology, The First College of Clinical Medical Science, China Three Gorges University,Yichang, Hubei 443001, China. Electronic address: lyf20041016@sohu.com.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia; Enzymoics, 7 Peterlee Place, Hebersham, NSW 2770, Australia; Novel Global Community Educational Foundation, 7 Peterlee Place, Hebersham, NSW 2770, Australia.
authors.forename: Mohammad Amjad
authors.initials: MA
authors.lastname: Kamal
authors.affiliation: Renhe Hospital, China Three Gorges University, Yichang, HuBei 443002, China. Electronic address: yuancf46@163.com.
authors.forename: Ding
authors.initials: D
authors.lastname: Yuan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000628:therapy; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010936:Plant Extracts / Q000494:pharmacology*; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology*; D031991:Pyracantha / Q000737:chemistry*; D012643:Selenium / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D010936:Plant Extracts; D011134:Polysaccharides; D004317:Doxorubicin; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D012643:Selenium
keywords: Apoptosis; Breast cancer; Nude mice; Pyracantha fortuneana; Selenium-enriched polysaccharides