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Enhanced antitumor efficacy of cisplatin in combination with HemoHIM in tumor-bearing mice.

Park HR, Ju EJ, Jo SK, Jung U, Kim SH, Yee ST - BMC Cancer (2009)

Bottom Line: Although cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome.HemoHIM itself did not inhibit melanoma cell growth in vitro, and did not disturb the effects of cisplatin in vitro.Also, HemoHIM reduced nephrotoxicity as seen by tubular cell of kidney destruction.

View Article: PubMed Central - HTML - PubMed

Affiliation: Radiation Resarch Division for Bio-Technology, Advanced Radiation Technology Institute, Jeongeup Campus of Korea Atomic Energy Research Institute (KAERI), 1266 Sinjeong-dong Jeongeup-si Jeonbuk 580-185, Republic of Korea. hrpark@kaeri.re.kr

ABSTRACT

Background: Although cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome. Also cisplatin accumulation shows toxicity to normal tissues. In this study, we examined the possibility of HemoHIM both to enhance anticancer effect with cisplatin and to reduce the side effects of cisplatin in melanoma-bearing mice.

Methods: HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of 3 edible herbs, Angelica Radix, Cnidium Rhizoma and Paeonia Radix. Anticancer effects of HemoHIM with cisplatin were evaluated in melanoma-bearing mice. We used a Cr51-release assay to measure the activity of NK/Tc cell and ELISA to evaluate the production of cytokines.

Results: In melanoma-bearing mice, cisplatin (4 mg/kg B.W.) reduced the size and weight of the solid tumors, and HemoHIM supplementation with cisplatin enhanced the decrease of both the tumor size (p < 0.1) and weight (p < 0.1). HemoHIM itself did not inhibit melanoma cell growth in vitro, and did not disturb the effects of cisplatin in vitro. However HemoHIM administration enhanced both NK cell and Tc cell activity in mice. Interestingly, HemoHIM increased the proportion of NK cells in the spleen. In melanoma-bearing mice treated with cisplatin, HemoHIM administration also increased the activity of NK cells and Tc cells and the IL-2 and IFN-gamma secretion from splenocytes, which seemed to contribute to the enhanced efficacy of cisplatin by HemoHIM. Also, HemoHIM reduced nephrotoxicity as seen by tubular cell of kidney destruction.

Conclusion: HemoHIM may be a beneficial supplement during cisplatin chemotherapy for enhancing the anti-tumor efficacy and reducing the toxicity of cisplatin.

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HemoHIM administration promotes immune responses for tumor surveillance in melanoma-bearing mice which were injected with cisplatin. All mice performed as described in figure 3 were sacrificed at 17 days after initial injection of cisplatin. (A)(B) The cancer cell killing activity of NK cells or Tc cells was determined by 51Cr release assay as described in Materials and Methods. (C)(D) Spleen lymphocytes were cultured with ConA (1 μg/ml). After 1 or 2 days, IL-2 and IFN-γ in culture supernatants were measured by ELISA as described in Materials and Methods. There were twenty one mice in each group. The spleens of three mice were pooled. Bars show the means ± SD of the septuple experiments. * p = 0.1, **p < 0.05 and ***p < 0.001 compared with only cisplatin treated group.
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Figure 5: HemoHIM administration promotes immune responses for tumor surveillance in melanoma-bearing mice which were injected with cisplatin. All mice performed as described in figure 3 were sacrificed at 17 days after initial injection of cisplatin. (A)(B) The cancer cell killing activity of NK cells or Tc cells was determined by 51Cr release assay as described in Materials and Methods. (C)(D) Spleen lymphocytes were cultured with ConA (1 μg/ml). After 1 or 2 days, IL-2 and IFN-γ in culture supernatants were measured by ELISA as described in Materials and Methods. There were twenty one mice in each group. The spleens of three mice were pooled. Bars show the means ± SD of the septuple experiments. * p = 0.1, **p < 0.05 and ***p < 0.001 compared with only cisplatin treated group.

Mentions: As the mechanisms for an enhanced anticancer efficacy of cisplatin in combination with HemoHIM in melanoma cell-bearing mice (Fig. 1), we concentrated on the activity of NK and Tc cells because these cells play an important role on cancer surveillance. As shown Fig. 5A and 5B, cisplatin injection alone in melanoma-bearing mice did not enhance or decrease the activity of NK cells and Tc cells. However, HemoHIM administration enhanced the activity of NK cells in melanoma-bearing mice which were treated with cisplatin (p = 0.1; Fig. 5A). In addition, the activity of Tc cells was enhanced significantly by HemoHIM administration (p < 0.05; Fig. 5B). These data suggested that the enhanced anticancer efficacy of cisplatin in combination with HemoHIM administration was due to the increase in the activity of NK and Tc cells that are in charge of tumor surveillance.


Enhanced antitumor efficacy of cisplatin in combination with HemoHIM in tumor-bearing mice.

Park HR, Ju EJ, Jo SK, Jung U, Kim SH, Yee ST - BMC Cancer (2009)

HemoHIM administration promotes immune responses for tumor surveillance in melanoma-bearing mice which were injected with cisplatin. All mice performed as described in figure 3 were sacrificed at 17 days after initial injection of cisplatin. (A)(B) The cancer cell killing activity of NK cells or Tc cells was determined by 51Cr release assay as described in Materials and Methods. (C)(D) Spleen lymphocytes were cultured with ConA (1 μg/ml). After 1 or 2 days, IL-2 and IFN-γ in culture supernatants were measured by ELISA as described in Materials and Methods. There were twenty one mice in each group. The spleens of three mice were pooled. Bars show the means ± SD of the septuple experiments. * p = 0.1, **p < 0.05 and ***p < 0.001 compared with only cisplatin treated group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2666758&req=5

Figure 5: HemoHIM administration promotes immune responses for tumor surveillance in melanoma-bearing mice which were injected with cisplatin. All mice performed as described in figure 3 were sacrificed at 17 days after initial injection of cisplatin. (A)(B) The cancer cell killing activity of NK cells or Tc cells was determined by 51Cr release assay as described in Materials and Methods. (C)(D) Spleen lymphocytes were cultured with ConA (1 μg/ml). After 1 or 2 days, IL-2 and IFN-γ in culture supernatants were measured by ELISA as described in Materials and Methods. There were twenty one mice in each group. The spleens of three mice were pooled. Bars show the means ± SD of the septuple experiments. * p = 0.1, **p < 0.05 and ***p < 0.001 compared with only cisplatin treated group.
Mentions: As the mechanisms for an enhanced anticancer efficacy of cisplatin in combination with HemoHIM in melanoma cell-bearing mice (Fig. 1), we concentrated on the activity of NK and Tc cells because these cells play an important role on cancer surveillance. As shown Fig. 5A and 5B, cisplatin injection alone in melanoma-bearing mice did not enhance or decrease the activity of NK cells and Tc cells. However, HemoHIM administration enhanced the activity of NK cells in melanoma-bearing mice which were treated with cisplatin (p = 0.1; Fig. 5A). In addition, the activity of Tc cells was enhanced significantly by HemoHIM administration (p < 0.05; Fig. 5B). These data suggested that the enhanced anticancer efficacy of cisplatin in combination with HemoHIM administration was due to the increase in the activity of NK and Tc cells that are in charge of tumor surveillance.

Bottom Line: Although cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome.HemoHIM itself did not inhibit melanoma cell growth in vitro, and did not disturb the effects of cisplatin in vitro.Also, HemoHIM reduced nephrotoxicity as seen by tubular cell of kidney destruction.

View Article: PubMed Central - HTML - PubMed

Affiliation: Radiation Resarch Division for Bio-Technology, Advanced Radiation Technology Institute, Jeongeup Campus of Korea Atomic Energy Research Institute (KAERI), 1266 Sinjeong-dong Jeongeup-si Jeonbuk 580-185, Republic of Korea. hrpark@kaeri.re.kr

ABSTRACT

Background: Although cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome. Also cisplatin accumulation shows toxicity to normal tissues. In this study, we examined the possibility of HemoHIM both to enhance anticancer effect with cisplatin and to reduce the side effects of cisplatin in melanoma-bearing mice.

Methods: HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of 3 edible herbs, Angelica Radix, Cnidium Rhizoma and Paeonia Radix. Anticancer effects of HemoHIM with cisplatin were evaluated in melanoma-bearing mice. We used a Cr51-release assay to measure the activity of NK/Tc cell and ELISA to evaluate the production of cytokines.

Results: In melanoma-bearing mice, cisplatin (4 mg/kg B.W.) reduced the size and weight of the solid tumors, and HemoHIM supplementation with cisplatin enhanced the decrease of both the tumor size (p < 0.1) and weight (p < 0.1). HemoHIM itself did not inhibit melanoma cell growth in vitro, and did not disturb the effects of cisplatin in vitro. However HemoHIM administration enhanced both NK cell and Tc cell activity in mice. Interestingly, HemoHIM increased the proportion of NK cells in the spleen. In melanoma-bearing mice treated with cisplatin, HemoHIM administration also increased the activity of NK cells and Tc cells and the IL-2 and IFN-gamma secretion from splenocytes, which seemed to contribute to the enhanced efficacy of cisplatin by HemoHIM. Also, HemoHIM reduced nephrotoxicity as seen by tubular cell of kidney destruction.

Conclusion: HemoHIM may be a beneficial supplement during cisplatin chemotherapy for enhancing the anti-tumor efficacy and reducing the toxicity of cisplatin.

Show MeSH
Related in: MedlinePlus