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Bee venom inhibits growth of human cervical tumors in mice.

Lee HL, Park SH, Kim TM, Jung YY, Park MH, Oh SH, Yun HS, Jun HO, Yoo HS, Han SB, Lee US, Yoon JH, Song MJ, Hong JT - Oncotarget (2015)

Bottom Line: Similar inhibitory effects of BV on cancer growth in primary human cervical cancer cells were also found.In addition, deletion of FAS, DR3 and DR6 by small interfering RNA significantly reversed BV-induced cell growth inhibitory effects as well as NF-κB inactivation.These results suggest that BV inhibits cervical tumor growth through enhancement of FAS, DR3 and DR6 expression via inhibition of NF-κB pathway.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy and Medical Research Center, Heungduk, Cheongju, Chungbuk, Republic of Korea.

ABSTRACT
We studied whether bee venom (BV) inhibits cervical tumor growth through enhancement of death receptor (DR) expressions and inactivation of nuclear factor kappa B (NF-κB) in mice. In vivo study showed that BV (1 mg/kg) inhibited tumor growth. Similar inhibitory effects of BV on cancer growth in primary human cervical cancer cells were also found. BV (1-5 μg/ml) also inhibited the growth of cancer cells, Ca Ski and C33Aby the induction of apoptotic cell death in a dose dependent manner. Agreed with cancer cell growth inhibition, expression of death receptors; FAS, DR3 and DR6, and DR downstream pro-apoptotic proteins including caspase-3 and Bax was concomitantly increased, but the NF-κB activity and the expression of Bcl-2 were inhibited by treatment with BV in tumor mice, human cancer cell and human tumor samples as well as cultured cancer cells. In addition, deletion of FAS, DR3 and DR6 by small interfering RNA significantly reversed BV-induced cell growth inhibitory effects as well as NF-κB inactivation. These results suggest that BV inhibits cervical tumor growth through enhancement of FAS, DR3 and DR6 expression via inhibition of NF-κB pathway.

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Anti-tumor activity of BV in cervical cancer xenograftGrowth inhibition (as assessed by tumor volume) of subcutaneously transplanted CA Ski xenografts mice treated with BV (1 mg/kg/ two times a week) for 4weeks. Xenografted mice (n = 10) were administrated intraperitoneally with saline (1 ml/kg) or BV (1 mg/kg). Tumor burden was measured once per week using a caliper, and calculated volume length (mm) × width (mm) × height (mm)/2. Tumor weight and volume are presented as means ± S.D. (A). The expression of apoptotic proteins was detected by western blotting using specific antibodies; DR3, DR6, FAS, cleaved caspase-3 (B). β-actin protein was used an internal control. Immunohistochemistry was used to determine expression levels of H&E, PCNA, DR3, DR6, p50 in nude mice xenograft tissues by the different treatments as described in the Materials and Methods Section (C). NF-κB activity in tumor tissues (D). All values represent mean ± SD from five animal tumor sections. *P < 0.05 indicates significantly different from the control group.
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Figure 1: Anti-tumor activity of BV in cervical cancer xenograftGrowth inhibition (as assessed by tumor volume) of subcutaneously transplanted CA Ski xenografts mice treated with BV (1 mg/kg/ two times a week) for 4weeks. Xenografted mice (n = 10) were administrated intraperitoneally with saline (1 ml/kg) or BV (1 mg/kg). Tumor burden was measured once per week using a caliper, and calculated volume length (mm) × width (mm) × height (mm)/2. Tumor weight and volume are presented as means ± S.D. (A). The expression of apoptotic proteins was detected by western blotting using specific antibodies; DR3, DR6, FAS, cleaved caspase-3 (B). β-actin protein was used an internal control. Immunohistochemistry was used to determine expression levels of H&E, PCNA, DR3, DR6, p50 in nude mice xenograft tissues by the different treatments as described in the Materials and Methods Section (C). NF-κB activity in tumor tissues (D). All values represent mean ± SD from five animal tumor sections. *P < 0.05 indicates significantly different from the control group.

Mentions: To elucidate the anti-tumor effect of BV in vivo, the tumor growth on cervical cancer cell xenograft bearing nude mice following BV (1 mg/kg) treatments was investigated. Since our previous studies in other cancer cells, 3 mg/kg was effective [4], thus, we used 1 mg/kg BV in cervical cancer. In Ca Ski xenograft studies, BV was administrated intraperitoneally two times per week for 4 weeks to mice which have tumors ranging from 100 to 300 mm3. Tumor volume was measured weekly, and all mice were killed at the end of experiment when tumors were dissected and weighted. The inhibitory effect of BV on growth of cervical tumor was significant in xenograft model mice (Figure 1A upper panel). Tumor weight and volume were significantly smaller in 1 mg/kg BV-treated compared with those saline-treated Ca Ski bearing mice (Figure 1A middle and lower panel). Expression of FAS, DR3 and DR6 and DR downstream pro-apoptotic proteins including cleavaged caspase-3, -8 and -9 was concomitantly increased (Figure 1B), but the NF-κB activity and expression of pI03BAB and nucleus p50 and p65 were inhibited in tumor tissues by treatment with BV (Figure 1C).


Bee venom inhibits growth of human cervical tumors in mice.

Lee HL, Park SH, Kim TM, Jung YY, Park MH, Oh SH, Yun HS, Jun HO, Yoo HS, Han SB, Lee US, Yoon JH, Song MJ, Hong JT - Oncotarget (2015)

Anti-tumor activity of BV in cervical cancer xenograftGrowth inhibition (as assessed by tumor volume) of subcutaneously transplanted CA Ski xenografts mice treated with BV (1 mg/kg/ two times a week) for 4weeks. Xenografted mice (n = 10) were administrated intraperitoneally with saline (1 ml/kg) or BV (1 mg/kg). Tumor burden was measured once per week using a caliper, and calculated volume length (mm) × width (mm) × height (mm)/2. Tumor weight and volume are presented as means ± S.D. (A). The expression of apoptotic proteins was detected by western blotting using specific antibodies; DR3, DR6, FAS, cleaved caspase-3 (B). β-actin protein was used an internal control. Immunohistochemistry was used to determine expression levels of H&E, PCNA, DR3, DR6, p50 in nude mice xenograft tissues by the different treatments as described in the Materials and Methods Section (C). NF-κB activity in tumor tissues (D). All values represent mean ± SD from five animal tumor sections. *P < 0.05 indicates significantly different from the control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4466684&req=5

Figure 1: Anti-tumor activity of BV in cervical cancer xenograftGrowth inhibition (as assessed by tumor volume) of subcutaneously transplanted CA Ski xenografts mice treated with BV (1 mg/kg/ two times a week) for 4weeks. Xenografted mice (n = 10) were administrated intraperitoneally with saline (1 ml/kg) or BV (1 mg/kg). Tumor burden was measured once per week using a caliper, and calculated volume length (mm) × width (mm) × height (mm)/2. Tumor weight and volume are presented as means ± S.D. (A). The expression of apoptotic proteins was detected by western blotting using specific antibodies; DR3, DR6, FAS, cleaved caspase-3 (B). β-actin protein was used an internal control. Immunohistochemistry was used to determine expression levels of H&E, PCNA, DR3, DR6, p50 in nude mice xenograft tissues by the different treatments as described in the Materials and Methods Section (C). NF-κB activity in tumor tissues (D). All values represent mean ± SD from five animal tumor sections. *P < 0.05 indicates significantly different from the control group.
Mentions: To elucidate the anti-tumor effect of BV in vivo, the tumor growth on cervical cancer cell xenograft bearing nude mice following BV (1 mg/kg) treatments was investigated. Since our previous studies in other cancer cells, 3 mg/kg was effective [4], thus, we used 1 mg/kg BV in cervical cancer. In Ca Ski xenograft studies, BV was administrated intraperitoneally two times per week for 4 weeks to mice which have tumors ranging from 100 to 300 mm3. Tumor volume was measured weekly, and all mice were killed at the end of experiment when tumors were dissected and weighted. The inhibitory effect of BV on growth of cervical tumor was significant in xenograft model mice (Figure 1A upper panel). Tumor weight and volume were significantly smaller in 1 mg/kg BV-treated compared with those saline-treated Ca Ski bearing mice (Figure 1A middle and lower panel). Expression of FAS, DR3 and DR6 and DR downstream pro-apoptotic proteins including cleavaged caspase-3, -8 and -9 was concomitantly increased (Figure 1B), but the NF-κB activity and expression of pI03BAB and nucleus p50 and p65 were inhibited in tumor tissues by treatment with BV (Figure 1C).

Bottom Line: Similar inhibitory effects of BV on cancer growth in primary human cervical cancer cells were also found.In addition, deletion of FAS, DR3 and DR6 by small interfering RNA significantly reversed BV-induced cell growth inhibitory effects as well as NF-κB inactivation.These results suggest that BV inhibits cervical tumor growth through enhancement of FAS, DR3 and DR6 expression via inhibition of NF-κB pathway.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy and Medical Research Center, Heungduk, Cheongju, Chungbuk, Republic of Korea.

ABSTRACT
We studied whether bee venom (BV) inhibits cervical tumor growth through enhancement of death receptor (DR) expressions and inactivation of nuclear factor kappa B (NF-κB) in mice. In vivo study showed that BV (1 mg/kg) inhibited tumor growth. Similar inhibitory effects of BV on cancer growth in primary human cervical cancer cells were also found. BV (1-5 μg/ml) also inhibited the growth of cancer cells, Ca Ski and C33Aby the induction of apoptotic cell death in a dose dependent manner. Agreed with cancer cell growth inhibition, expression of death receptors; FAS, DR3 and DR6, and DR downstream pro-apoptotic proteins including caspase-3 and Bax was concomitantly increased, but the NF-κB activity and the expression of Bcl-2 were inhibited by treatment with BV in tumor mice, human cancer cell and human tumor samples as well as cultured cancer cells. In addition, deletion of FAS, DR3 and DR6 by small interfering RNA significantly reversed BV-induced cell growth inhibitory effects as well as NF-κB inactivation. These results suggest that BV inhibits cervical tumor growth through enhancement of FAS, DR3 and DR6 expression via inhibition of NF-κB pathway.

Show MeSH
Related in: MedlinePlus