Background. Kefir is a unique cultured product that contains beneficial probiotics. Kefir culture from other parts of the world exhibits numerous beneficial qualities such as anti-inflammatory, immunomodulation, and anticancer effects. Nevertheless, kefir cultures from different parts of the world exert different effects because of variation in culture conditions and media. Breast cancer is the leading cancer in women, and metastasis is the major cause of death associated with breast cancer. The antimetastatic and antiangiogenic effects of kefir water made from kefir grains cultured in Malaysia were studied in 4T1 breast cancer cells. Methods. 4T1 cancer cells were treated with kefir water in vitro to assess its antimigration and anti-invasion effects. BALB/c mice were injected with 4T1 cancer cells and treated orally with kefir water for 28 days. Results. Kefir water was cytotoxic toward 4T1 cells at IC50 (half-maximal inhibitory concentration) of 12.5 and 8.33 mg/mL for 48 and 72 hours, respectively. A significant reduction in tumor size and weight (0.9132 ± 0.219 g) and a substantial increase in helper T cells (5-fold) and cytotoxic T cells (7-fold) were observed in the kefir water–treated group. Proinflammatory and proangiogenic markers were significantly reduced in the kefir water–treated group. Conclusions. Kefir water inhibited tumor proliferation in vitro and in vivo mainly through cancer cell apoptosis, immunomodulation by stimulating T helper cells and cytotoxic T cells, and anti-inflammatory, antimetastatic, and antiangiogenesis effects. This study brought out the potential of the probiotic beverage kefir water in cancer treatment.
Flavokawain A is a chalcone that can be found in the kava-kava plant (Piper methsyticum) extract. The kava-kava plant has been reported to possess anti-cancer, anti-inflammatory and antinociceptive activities. The state of the immune system, and the inflammatory process play vital roles in the progression of cancer. The immunomodulatary effects and the anti-inflammatory effects of flavokawain A in a breast cancer murine model have not been studied yet. Thus, this study aimed to elucidate the basic mechanism as to how flavokawain A regulates and enhance the immune system as well as impeding the inflammatory process in breast cancer-challenged mice. Based on our study, it is interesting to note that flavokawain A increased the T cell population; both Th1 cells and CTLs, aside from the natural killer cells. The levels of IFN-γ and IL-2 were also elevated in the serum of flavokawain A-treated mice. Apart from that, flavokawain A also decreased the weight and volume of the tumor, and managed to induce apoptosis in them. In terms of inflammation, flavokawain A-treated mice had reduced level of major pro-inflammatory mediators; NO, iNOS, NF-KB, ICAM and COX-2. Overall, flavokawain A has the potential to not only enhance antitumor immunity, but also prevents the inflammatory process in a cancer-prone microenvironment.
Flavokawain B (FKB) is a naturally occurring chalcone that can be isolated through the root extracts of the kava-kava plant (Piper methysticum). It can also be synthesized chemically to increase the yield. This compound is a promising candidate as a biological agent, as it is reported to be involved in a wide range of biological activities. Furthermore, FKB was reported to have antitumorigenic effects in several cancer cell lines in vitro. However, the in vivo antitumor effects of FKB have not been reported on yet. Breast cancer is one of the major causes of cancer-related deaths in the world today. Any potential treatment should not only impede the growth of the tumor, but also modulate the immune system efficiently and inhibit the formation of secondary tumors. As presented in our study, FKB induced apoptosis in 4T1 tumors in vivo, as evidenced by the terminal deoxynucleotidyl transferase dUTP nick end labeling and hematoxylin and eosin staining of the tumor. FKB also regulated the immune system by increasing both helper and cytolytic T-cell and natural killer cell populations. In addition, FKB also enhanced the levels of interleukin 2 and interferon gamma but suppressed interleukin 1B. Apart from that, FKB was also found to inhibit metastasis, as evaluated by clonogenic assay, bone marrow smearing assay, real-time polymerase chain reaction, Western blot, and proteome profiler analysis. All in all, FKB may serve as a promising anticancer agent, especially in treating breast cancer.
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