Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Center, Riyadh, P.O. Box 3354, Riyadh, 11211, Saudi Arabia.
Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Center, Riyadh, P.O. Box 3354, Riyadh, 11211, Saudi Arabia.
Biomed Pharmacother. 2019 Oct;118:109376. doi: 10.1016/j.biopha.2019.109376. Epub 2019 Aug 28.
Many Muslims believe that water from the Zamzam well is the cure for every disease. Zamzam water (ZW) is naturally alkaline water consumed by millions of people worldwide. The current study investigated the effect of ZW on cell viability and apoptosis in breast, colorectal and ovarian cancer cell lines and compared the effect with that of drinking water (DW).
Three different ZW samples collected from different sources at different periods were used. To balance the tonicity, ZW and DW were buffered using PBS and the pH was adjusted to 7.4. For the treatment, ZW and DW were diluted to 50% with RPMI medium (10% FBS). Cancer cell lines were treated with ZW or DW, with and without chemotherapeutic agents, for 24 h. Apoptosis was measured using flow cytometry whilst the level of protein expression was determined by Western blotting.
The results showed that treatment with ZW significantly increased cell proliferation compared to DW control. Treatment with ZW significantly suppressed the effect of chemotherapeutic agents on decreasing cell viability and inducing apoptosis in all the cancer cell lines compared to chemotherapeutic agents alone treated in DW. Furthermore, ZW treatment increased the phosphorylation of CRAF, MEK1/2, ERK1/2 and P38 proteins in these cell lines. Notably, treatment with ZW suppressed the effect of chemotherapy-induced reduction of CRAF, MEK1/2, ERK1/2 and P38 phosphorylation in breast and ovarian cancer cell lines. We also showed that silencing of ERK1/2 significantly increased the chemotherapy-induced apoptosis in breast and colorectal cancer cell lines. These data suggest that MAPK proteins; especially activated ERK1/2 may play a role in ZW mediated suppression of chemotherapy-induced cell death.
These findings clearly demonstrate that ZW protects cancer cells from chemotherapy-induced apoptosis through activation of the ERK1/2-MAPK signaling pathway.
许多穆斯林认为，来自扎姆扎姆泉的水可以治愈各种疾病。扎姆扎姆水（ZW）是一种天然碱性水，被世界各地数百万人饮用。本研究调查了 ZW 对乳腺癌、结直肠癌和卵巢癌细胞系细胞活力和细胞凋亡的影响，并将其与饮用水（DW）的影响进行了比较。
使用三种不同来源和不同时期采集的 ZW 样本。为了平衡渗透压，ZW 和 DW 均使用 PBS 缓冲，pH 值调至 7.4。对于处理，ZW 和 DW 用 RPMI 培养基（10%FBS）稀释至 50%。用 ZW 或 DW 处理癌细胞系，有或没有化疗药物，处理 24 小时。用流式细胞术测量细胞凋亡，用 Western blot 测定蛋白表达水平。
结果表明，与 DW 对照组相比，ZW 处理显著增加了细胞增殖。与单独用 DW 处理的化疗药物相比，ZW 处理显著抑制了化疗药物降低细胞活力和诱导细胞凋亡的作用。此外，ZW 处理增加了这些细胞系中 CRAF、MEK1/2、ERK1/2 和 P38 蛋白的磷酸化。值得注意的是，ZW 处理抑制了化疗药物诱导的乳腺癌和卵巢癌细胞系中 CRAF、MEK1/2、ERK1/2 和 P38 磷酸化的减少。我们还表明，ERK1/2 的沉默显著增加了乳腺癌和结直肠癌细胞系中化疗诱导的细胞凋亡。这些数据表明，MAPK 蛋白；特别是激活的 ERK1/2，可能在 ZW 介导的抑制化疗诱导的细胞死亡中起作用。
这些发现清楚地表明，ZW 通过激活 ERK1/2-MAPK 信号通路来保护癌细胞免受化疗诱导的细胞凋亡。
