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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

In vitro migration/invasion results in 4T1 cells upon treatment with flavokawain B.Notes: (A) Wound healing analysis of 4T1 cells after treatment with three concentrations of flavokawain B for 24 hours. (B) Percentage of migrated cells in the in vitro migration assay of 4T1 cells through a Boyden chamber alongside three different doses of flavokawain B for 18 hours. (C) Percentage of invaded cells in the in vitro invasion assay of 4T1 cells through a basement membrane with three different concentrations of flavokawain B for 18 hours. Images (B and C) were taken at 20× magnification, and were stained with crystal violet. All values are represented as mean ± standard error of the mean; significance was set at P<0.05. *P<0.05.
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f3-dddt-9-1401: In vitro migration/invasion results in 4T1 cells upon treatment with flavokawain B.Notes: (A) Wound healing analysis of 4T1 cells after treatment with three concentrations of flavokawain B for 24 hours. (B) Percentage of migrated cells in the in vitro migration assay of 4T1 cells through a Boyden chamber alongside three different doses of flavokawain B for 18 hours. (C) Percentage of invaded cells in the in vitro invasion assay of 4T1 cells through a basement membrane with three different concentrations of flavokawain B for 18 hours. Images (B and C) were taken at 20× magnification, and were stained with crystal violet. All values are represented as mean ± standard error of the mean; significance was set at P<0.05. *P<0.05.

Mentions: To determine the effects of FKB on the in vitro motility and invasiveness of 4T1 cells, three assays were conducted. As depicted in Figure 3A, the wound healing analysis was performed to observe whether FKB impeded the migration of the 4T1 cells toward the center of the wound. After 24 hours of incubation, the percentage of wound closure decreased substantially in the treated samples. The percentage of wound closures declined from 100% to 54.26%±6.14% in the 9 μg/mL treatment group, 43.6%±2.41% in the 13.5 μg/mL treatment group, and 33.72%±2.78% in the 28 μg/mL treatment group. To observe the effects of FKB on the migration of 4T1 cells in a three-dimensional setting, the Boyden transwell chamber assay was performed. As depicted in Figure 3B, the percentage of migrated cells also decreased significantly in the treatment group. In terms of the invasiveness of 4T1 cells, the ability is reduced on treatment with FKB, as presented in Figure 3C.


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)

In vitro migration/invasion results in 4T1 cells upon treatment with flavokawain B.Notes: (A) Wound healing analysis of 4T1 cells after treatment with three concentrations of flavokawain B for 24 hours. (B) Percentage of migrated cells in the in vitro migration assay of 4T1 cells through a Boyden chamber alongside three different doses of flavokawain B for 18 hours. (C) Percentage of invaded cells in the in vitro invasion assay of 4T1 cells through a basement membrane with three different concentrations of flavokawain B for 18 hours. Images (B and C) were taken at 20× magnification, and were stained with crystal violet. All values are represented as mean ± standard error of the mean; significance was set at P<0.05. *P<0.05.
© Copyright Policy
Related In: Results  -  Collection

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

f3-dddt-9-1401: In vitro migration/invasion results in 4T1 cells upon treatment with flavokawain B.Notes: (A) Wound healing analysis of 4T1 cells after treatment with three concentrations of flavokawain B for 24 hours. (B) Percentage of migrated cells in the in vitro migration assay of 4T1 cells through a Boyden chamber alongside three different doses of flavokawain B for 18 hours. (C) Percentage of invaded cells in the in vitro invasion assay of 4T1 cells through a basement membrane with three different concentrations of flavokawain B for 18 hours. Images (B and C) were taken at 20× magnification, and were stained with crystal violet. All values are represented as mean ± standard error of the mean; significance was set at P<0.05. *P<0.05.
Mentions: To determine the effects of FKB on the in vitro motility and invasiveness of 4T1 cells, three assays were conducted. As depicted in Figure 3A, the wound healing analysis was performed to observe whether FKB impeded the migration of the 4T1 cells toward the center of the wound. After 24 hours of incubation, the percentage of wound closure decreased substantially in the treated samples. The percentage of wound closures declined from 100% to 54.26%±6.14% in the 9 μg/mL treatment group, 43.6%±2.41% in the 13.5 μg/mL treatment group, and 33.72%±2.78% in the 28 μg/mL treatment group. To observe the effects of FKB on the migration of 4T1 cells in a three-dimensional setting, the Boyden transwell chamber assay was performed. As depicted in Figure 3B, the percentage of migrated cells also decreased significantly in the treatment group. In terms of the invasiveness of 4T1 cells, the ability is reduced on treatment with FKB, as presented in Figure 3C.

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