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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

Tumor size and weight harvested from the control and flavokawain b-treated mice.Notes: (A) Picture of the tumors harvested from the control and flavokawain B (50 mg/kg)-treated mice. (B) Volume of the tumors was measured using a vernier caliper. (C) Weight of the tumors was measured after being harvested from the mice after 28 days of treatment. Each value represents the mean ± standard deviation for triplicates (*P<0.05); n=7 mice per group.
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f4-dddt-9-1401: Tumor size and weight harvested from the control and flavokawain b-treated mice.Notes: (A) Picture of the tumors harvested from the control and flavokawain B (50 mg/kg)-treated mice. (B) Volume of the tumors was measured using a vernier caliper. (C) Weight of the tumors was measured after being harvested from the mice after 28 days of treatment. Each value represents the mean ± standard deviation for triplicates (*P<0.05); n=7 mice per group.

Mentions: FKB managed to reduce the size of the tumor after 28 days of treatment, as depicted in Figure 4A. Likewise, in Figure 4B, the tumor volume also decreased from 700±70 mm3 in the untreated group to 462.5±74 mm3 in the FKB-treated group. The weight of the tumor in the untreated group was 0.617±0.013 g, whereas this value decreased to 0.44±0.037 g in the treatment group, as depicted in Figure 4C. Moreover, on the basis of the TUNEL analysis, the number of apoptotic cells in the tumors increased in the FKB-treated tumors, as in Figure 5. In addition, according to the H&E staining, as illustrated in Figure 5, the number of mitotic cells decreased in the FKB-treated tumors.


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)

Tumor size and weight harvested from the control and flavokawain b-treated mice.Notes: (A) Picture of the tumors harvested from the control and flavokawain B (50 mg/kg)-treated mice. (B) Volume of the tumors was measured using a vernier caliper. (C) Weight of the tumors was measured after being harvested from the mice after 28 days of treatment. Each value represents the mean ± standard deviation for triplicates (*P<0.05); n=7 mice per group.
© Copyright Policy
Related In: Results  -  Collection

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

f4-dddt-9-1401: Tumor size and weight harvested from the control and flavokawain b-treated mice.Notes: (A) Picture of the tumors harvested from the control and flavokawain B (50 mg/kg)-treated mice. (B) Volume of the tumors was measured using a vernier caliper. (C) Weight of the tumors was measured after being harvested from the mice after 28 days of treatment. Each value represents the mean ± standard deviation for triplicates (*P<0.05); n=7 mice per group.
Mentions: FKB managed to reduce the size of the tumor after 28 days of treatment, as depicted in Figure 4A. Likewise, in Figure 4B, the tumor volume also decreased from 700±70 mm3 in the untreated group to 462.5±74 mm3 in the FKB-treated group. The weight of the tumor in the untreated group was 0.617±0.013 g, whereas this value decreased to 0.44±0.037 g in the treatment group, as depicted in Figure 4C. Moreover, on the basis of the TUNEL analysis, the number of apoptotic cells in the tumors increased in the FKB-treated tumors, as in Figure 5. In addition, according to the H&E staining, as illustrated in Figure 5, the number of mitotic cells decreased in the FKB-treated tumors.

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