Yuan Chengfu, Wang Changdong, Wang Junjie, Kumar Vikas, Anwar Firoz, Xiao Fangxiang, Mushtaq Gohar, Liu Yufei, Kamal Mohammad Amjad, Yuan Ding
College of Medical Science, China Three Gorges University, Yichang, HuBei 443002, China; Renhe Hospital, China Three Gorges University, Yichang, HuBei 443002, China.
Molecular Medicine & Cancer Research Center, Chongqing Medical University, Chong qing 400016, China.
Nutr Res. 2016 Nov;36(11):1243-1254. doi: 10.1016/j.nutres.2016.09.012. Epub 2016 Oct 2.
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.
乳腺癌是女性癌症相关死亡的第二大原因。目前的乳腺癌治疗方法存在不良副作用。含硒多糖对人类有多种健康益处。火棘（P. fortuneana）含有丰富的硒多糖。我们假设火棘中的含硒多糖通过抑制生长和诱导凋亡对乳腺癌具有抗癌活性。本研究旨在评估火棘含硒多糖的抗癌作用及其潜在机制。对含硒多糖进行了纯化。分析了它们的性质和单糖组成。检测了它们对细胞生长、周期蛋白表达、凋亡及凋亡相关蛋白的影响，以及对小鼠异种移植模型中肿瘤生长的影响。该提取物含有93.7%（w/w）的碳水化合物、2.1%（w/w）的糖醛酸和3.7μg/g的硒，被认为是硒结合多糖（Se-PFPs）。体外研究表明，用Se-PFPs处理三阴性乳腺癌（TNBC）MDA-MB-231细胞：（1）通过抑制CDC25C-CyclinB1/CDC2途径使细胞停滞在G2期，从而剂量依赖性地抑制细胞生长；（2）导致凋亡，伴随p53、Bax、Puma和Noxa增加，Bcl2减少，Bax/Bcl2比值增加，半胱天冬酶3/9活性增加，表明其对p53介导的细胞色素c-半胱天冬酶途径有影响。用Se-PFPs处理携带MDA-MB-231来源异种移植肿瘤的裸鼠可显著降低肿瘤生长，且不改变体重，证实其具有抗肿瘤活性且无毒性副作用。Se-PFPs增强了阿霉素的细胞毒性作用。结论是，火棘中的含硒多糖能有效抑制TNBC细胞的生长并诱导其凋亡，可成为TNBC潜在的抗癌药物。
