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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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Related in: MedlinePlus

Effect of HemoHIM on cancer cell killing activity of NK cells and Tc cells. C57BL/6 mice were orally administrated with HemoHIM (100 mg/kg B.W.) and injected with MMC-treated B16F0 melanoma (1 × 106cell/mouse) into peritoneal cavity. 10 days after cancer cell inoculation, the cancer cell killing activity of NK cells or Tc cells was determined by 51Cr release assay as described in Materials and Methods. There were six mice in each group. Data show the Mean ± SD. * p = 0.06 and ** p < 0.05 compared with mice administrated water.
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Figure 4: Effect of HemoHIM on cancer cell killing activity of NK cells and Tc cells. C57BL/6 mice were orally administrated with HemoHIM (100 mg/kg B.W.) and injected with MMC-treated B16F0 melanoma (1 × 106cell/mouse) into peritoneal cavity. 10 days after cancer cell inoculation, the cancer cell killing activity of NK cells or Tc cells was determined by 51Cr release assay as described in Materials and Methods. There were six mice in each group. Data show the Mean ± SD. * p = 0.06 and ** p < 0.05 compared with mice administrated water.

Mentions: Because HemoHIM did not directly kill cancer cells, we thought that the activity of immune cells which were in charge of tumor surveillance may be enhanced by HemoHIM. We investigated the cancer cell-killing activity of NK and Tc cells, as they are in charge of innate and adaptive immunity against tumor, respectively. To investigate the activity of Tc cell, we used the mice which were immunized with mitomycin C (MMC)-treated melanoma cells. As shown in Fig. 4A and 4B, HemoHIM administration enhanced cancer cell-killing activity of NK cells and Tc cells in MMC-treated melanoma cell-bearing mice (p < 0.05 and p = 0.06, respectively). Also, the proportion of NK cell in spleen lymphocytes was increased by HemoHIM administration (p < 0.05), but not the proportion of Tc cells. Specially, these results were important because NK cells take part in both innate and adaptive immunity, and are regarded as interfaces between the innate and adaptive immune systems [28].


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)

Effect of HemoHIM on cancer cell killing activity of NK cells and Tc cells. C57BL/6 mice were orally administrated with HemoHIM (100 mg/kg B.W.) and injected with MMC-treated B16F0 melanoma (1 × 106cell/mouse) into peritoneal cavity. 10 days after cancer cell inoculation, the cancer cell killing activity of NK cells or Tc cells was determined by 51Cr release assay as described in Materials and Methods. There were six mice in each group. Data show the Mean ± SD. * p = 0.06 and ** p < 0.05 compared with mice administrated water.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Effect of HemoHIM on cancer cell killing activity of NK cells and Tc cells. C57BL/6 mice were orally administrated with HemoHIM (100 mg/kg B.W.) and injected with MMC-treated B16F0 melanoma (1 × 106cell/mouse) into peritoneal cavity. 10 days after cancer cell inoculation, the cancer cell killing activity of NK cells or Tc cells was determined by 51Cr release assay as described in Materials and Methods. There were six mice in each group. Data show the Mean ± SD. * p = 0.06 and ** p < 0.05 compared with mice administrated water.
Mentions: Because HemoHIM did not directly kill cancer cells, we thought that the activity of immune cells which were in charge of tumor surveillance may be enhanced by HemoHIM. We investigated the cancer cell-killing activity of NK and Tc cells, as they are in charge of innate and adaptive immunity against tumor, respectively. To investigate the activity of Tc cell, we used the mice which were immunized with mitomycin C (MMC)-treated melanoma cells. As shown in Fig. 4A and 4B, HemoHIM administration enhanced cancer cell-killing activity of NK cells and Tc cells in MMC-treated melanoma cell-bearing mice (p < 0.05 and p = 0.06, respectively). Also, the proportion of NK cell in spleen lymphocytes was increased by HemoHIM administration (p < 0.05), but not the proportion of Tc cells. Specially, these results were important because NK cells take part in both innate and adaptive immunity, and are regarded as interfaces between the innate and adaptive immune systems [28].

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