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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

Quantitative polymerase chain reaction analysis was done to detect the messenger RNA (mRNA) levels of nuclear factor (NF)-κB, inducible nitric oxide synthase (iNOS), intercellular adhesion molecule 1 (ICAM1), and C-MYC in the tumors of the control and flavokawain B (50 mg/kg/day)-treated mice.Notes: Each value represents the mean ± standard deviation for triplicates; *P<0.05.
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f11-dddt-9-1401: Quantitative polymerase chain reaction analysis was done to detect the messenger RNA (mRNA) levels of nuclear factor (NF)-κB, inducible nitric oxide synthase (iNOS), intercellular adhesion molecule 1 (ICAM1), and C-MYC in the tumors of the control and flavokawain B (50 mg/kg/day)-treated mice.Notes: Each value represents the mean ± standard deviation for triplicates; *P<0.05.

Mentions: The level of nitric oxide in the tumors was also measured. As shown in Figure 10, the level of nitric oxide in FKB-treated tumors was reduced when compared with the control. Real-time polymerase chain reaction was conducted to measure the levels of messenger RNA of four different genes in the tumor lysates. As presented in Figure 11, the levels of nuclear factor κB, inducible nitric oxide synthase, intercellular adhesion molecule 1, and C-MYC declined in the FKB-treated mice. This pattern was also seen in the protein level of VEGF, as illustrated in Figure 12. Furthermore, on the basis of the proteome profiler analysis, the levels of several angiogenesis-related proteins were also decreased in the FKB-treated group, as shown in Figure 13. These proteins included angiogenin, TIMP-1, coagulation factor 3, SDF-1, serpin E1, FGF Acidic, FGF Basic, TSP-2, Endothelin 1, IP-10, KC, PDGF-AA, PDGF-BB, Pentraxin 3, IGFBP-1, and IGFBP-2.


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)

Quantitative polymerase chain reaction analysis was done to detect the messenger RNA (mRNA) levels of nuclear factor (NF)-κB, inducible nitric oxide synthase (iNOS), intercellular adhesion molecule 1 (ICAM1), and C-MYC in the tumors of the control and flavokawain B (50 mg/kg/day)-treated mice.Notes: Each value represents the mean ± standard deviation for triplicates; *P<0.05.
© Copyright Policy
Related In: Results  -  Collection

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

f11-dddt-9-1401: Quantitative polymerase chain reaction analysis was done to detect the messenger RNA (mRNA) levels of nuclear factor (NF)-κB, inducible nitric oxide synthase (iNOS), intercellular adhesion molecule 1 (ICAM1), and C-MYC in the tumors of the control and flavokawain B (50 mg/kg/day)-treated mice.Notes: Each value represents the mean ± standard deviation for triplicates; *P<0.05.
Mentions: The level of nitric oxide in the tumors was also measured. As shown in Figure 10, the level of nitric oxide in FKB-treated tumors was reduced when compared with the control. Real-time polymerase chain reaction was conducted to measure the levels of messenger RNA of four different genes in the tumor lysates. As presented in Figure 11, the levels of nuclear factor κB, inducible nitric oxide synthase, intercellular adhesion molecule 1, and C-MYC declined in the FKB-treated mice. This pattern was also seen in the protein level of VEGF, as illustrated in Figure 12. Furthermore, on the basis of the proteome profiler analysis, the levels of several angiogenesis-related proteins were also decreased in the FKB-treated group, as shown in Figure 13. These proteins included angiogenin, TIMP-1, coagulation factor 3, SDF-1, serpin E1, FGF Acidic, FGF Basic, TSP-2, Endothelin 1, IP-10, KC, PDGF-AA, PDGF-BB, Pentraxin 3, IGFBP-1, and IGFBP-2.

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