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In vivo antitumor and antimetastatic effects of flavokawain B in 4T1 breast cancer cell-challenged mice.

Abu N, Mohamed NE, Yeap SK, Lim KL, Akhtar MN, Zulfadli AJ, Kee BB, Abdullah MP, Omar AR, Alitheen NB - Drug Des Devel Ther (2015)

Bottom Line: 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.All in all, FKB may serve as a promising anticancer agent, especially in treating breast cancer.

View Article: PubMed Central - PubMed

Affiliation: Bright Sparks Unit, Universiti Malaya, Kuala Lumpur, Malaysia ; Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Selangor Darul Ehsan, Malaysia.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Flow cytometry analysis of four immune markers (CD3, CD4, CD8, and NK1.1) on the splenocytes of both the control and flavokawain B (50 mg/kg)-treated mice.Notes: Each value represents the mean ± standard error of the mean for triplicates. Significance is set at *P<0.05; n=7 mice per group.
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f6-dddt-9-1401: Flow cytometry analysis of four immune markers (CD3, CD4, CD8, and NK1.1) on the splenocytes of both the control and flavokawain B (50 mg/kg)-treated mice.Notes: Each value represents the mean ± standard error of the mean for triplicates. Significance is set at *P<0.05; n=7 mice per group.

Mentions: To understand the effects of FKB on the important immune markers, immunophenotyping of the splenocyte cell population was conducted. As depicted in Figure 6, the population of the CD4/CD3 T-cell population increased significantly in the FKB-treated splenocytes. A similar pattern was also observed in the population of CD8/CD4 T-cells. In addition, the population of both natural killer (NK) 1.1/CD3+ and NK1.1/CD3− cells was elevated slightly, even though it is not statistically significant. To further elucidate the mechanistic action of FKB, the levels of expression of several important cytokines was also measured, as presented in Figure 7. The level of IL-2 in the serum of the control mice was 35.09±7.54 pg/mL, whereas in the FKB group, the level of IL-2 increased to 141.11±1.22 pg/mL. Moreover, as depicted in Figure 7, the level of IFN-γ also increased from 94.21±1.91 pg/mL in the control group to 174.82±0.52 pg/mL in the FKB-treated serum. Moreover, on the basis of the level of IL-1β, the value in the control group, 666.67±7.63 pg/mL, decreased to 433.33±2.88 pg/mL in the FKB-treated mice. Moreover, as depicted in Table 3, the red blood count in FKB-treated mice increased compared with in the control.


In vivo antitumor and antimetastatic effects of flavokawain B in 4T1 breast cancer cell-challenged mice.

Abu N, Mohamed NE, Yeap SK, Lim KL, Akhtar MN, Zulfadli AJ, Kee BB, Abdullah MP, Omar AR, Alitheen NB - Drug Des Devel Ther (2015)

Flow cytometry analysis of four immune markers (CD3, CD4, CD8, and NK1.1) on the splenocytes of both the control and flavokawain B (50 mg/kg)-treated mice.Notes: Each value represents the mean ± standard error of the mean for triplicates. Significance is set at *P<0.05; n=7 mice per group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4358690&req=5

f6-dddt-9-1401: Flow cytometry analysis of four immune markers (CD3, CD4, CD8, and NK1.1) on the splenocytes of both the control and flavokawain B (50 mg/kg)-treated mice.Notes: Each value represents the mean ± standard error of the mean for triplicates. Significance is set at *P<0.05; n=7 mice per group.
Mentions: To understand the effects of FKB on the important immune markers, immunophenotyping of the splenocyte cell population was conducted. As depicted in Figure 6, the population of the CD4/CD3 T-cell population increased significantly in the FKB-treated splenocytes. A similar pattern was also observed in the population of CD8/CD4 T-cells. In addition, the population of both natural killer (NK) 1.1/CD3+ and NK1.1/CD3− cells was elevated slightly, even though it is not statistically significant. To further elucidate the mechanistic action of FKB, the levels of expression of several important cytokines was also measured, as presented in Figure 7. The level of IL-2 in the serum of the control mice was 35.09±7.54 pg/mL, whereas in the FKB group, the level of IL-2 increased to 141.11±1.22 pg/mL. Moreover, as depicted in Figure 7, the level of IFN-γ also increased from 94.21±1.91 pg/mL in the control group to 174.82±0.52 pg/mL in the FKB-treated serum. Moreover, on the basis of the level of IL-1β, the value in the control group, 666.67±7.63 pg/mL, decreased to 433.33±2.88 pg/mL in the FKB-treated mice. Moreover, as depicted in Table 3, the red blood count in FKB-treated mice increased compared with in the control.

Bottom Line: 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.All in all, FKB may serve as a promising anticancer agent, especially in treating breast cancer.

View Article: PubMed Central - PubMed

Affiliation: Bright Sparks Unit, Universiti Malaya, Kuala Lumpur, Malaysia ; Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Selangor Darul Ehsan, Malaysia.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus