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Apoptosis Induction in Primary Human Colorectal Cancer Cell Lines and Retarded Tumor Growth in SCID Mice by Sulforaphane.

Chen MJ, Tang WY, Hsu CW, Tsai YT, Wu JF, Lin CW, Cheng YM, Hsu YC - Evid Based Complement Alternat Med (2011)

Bottom Line: In addition, treated cells showed nuclear apoptotic morphology that coincided with an activation of caspase-3, and loss of mitochondrial membrane potential (ΔΨm).Incubations at higher SFN doses (12.5 and 25 μM) resulted in cleavage of procaspase-3 and elevated caspase-2, -3, -8, and -9 activity, suggesting that the induction of apoptosis and the sulforaphane-induced mitosis delay at the lower dose are independently regulated.Daily SFN s.c. injections (400 micromol/kg/d for 3 weeks) in severe combined immunodeficient mice with primary human CRC (CP1 to CP5) s.c. tumors resulted in a decrease of mean tumor weight by 70% compared with vehicle-treated controls.

View Article: PubMed Central - PubMed

Affiliation: Division of Traumatology, Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan.

ABSTRACT
We have investigated the anticancer effects of the dietary isothiocyanate sulforaphane (SFN) on colorectal cancer (CRC), using primary cancer cells lines isolated from five Taiwanese colorectal cancer patients as the model for colorectal cancer. SFN-treated cells accumulated in metaphase (SFN 6.25 μM) and subG1 (SFN 12.5 and 25 μM) as determined by flow cytometry. In addition, treated cells showed nuclear apoptotic morphology that coincided with an activation of caspase-3, and loss of mitochondrial membrane potential (ΔΨm). Incubations at higher SFN doses (12.5 and 25 μM) resulted in cleavage of procaspase-3 and elevated caspase-2, -3, -8, and -9 activity, suggesting that the induction of apoptosis and the sulforaphane-induced mitosis delay at the lower dose are independently regulated. Daily SFN s.c. injections (400 micromol/kg/d for 3 weeks) in severe combined immunodeficient mice with primary human CRC (CP1 to CP5) s.c. tumors resulted in a decrease of mean tumor weight by 70% compared with vehicle-treated controls. Our findings suggest that, in addition to the known effects on cancer prevention, sulforaphane may have antitumor activity in established colorectal cancer.

No MeSH data available.


Related in: MedlinePlus

SFN inhibits in vivo tumor growth. (a) Effects of SFN on tumor growth of SCID mice subcutaneously inoculated with primary human CRC cell lines. The results showed that SFN 400 μM inhibited tumor growth significantly in both cancer xenografts. (b) Inhibition of tumor growth was compared among tested groups. The inhibitory ratio was normalized to the negative control (PBS group) (values represent percent of control, n = 3 *P < 0.05 versus PBS group).
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fig7: SFN inhibits in vivo tumor growth. (a) Effects of SFN on tumor growth of SCID mice subcutaneously inoculated with primary human CRC cell lines. The results showed that SFN 400 μM inhibited tumor growth significantly in both cancer xenografts. (b) Inhibition of tumor growth was compared among tested groups. The inhibitory ratio was normalized to the negative control (PBS group) (values represent percent of control, n = 3 *P < 0.05 versus PBS group).

Mentions: Macroscopic tumors were observed on day 21, after injection of SFN and PBS control groups of nude mice. After injection of SFN 400 μM in the experimental group, tumors developed slowly. After 21 days of injection of SFN, no mice had died in the three groups, and the tumors were resected and measured. Small pale tumor nodules were observed in the tumors, whereas red and hypervascularized large tumors were present in the PBS control and SFN 200 μM tumor cells. The average size of tumors in the experimental group (400 μM) was 52.99% (tumor image size) and 28.70% (tumor weight), much less than the average size of the PBS control (100%) (Figure 7(b)). The results indicated that SFN could decrease tumorigenesis by inhibiting neovascularization in tumors in vivo. SFN might also have inhibitory actions on surrounding tumor tissues and indirectly inhibit tumorigenesis (Figure 7(a)).


Apoptosis Induction in Primary Human Colorectal Cancer Cell Lines and Retarded Tumor Growth in SCID Mice by Sulforaphane.

Chen MJ, Tang WY, Hsu CW, Tsai YT, Wu JF, Lin CW, Cheng YM, Hsu YC - Evid Based Complement Alternat Med (2011)

SFN inhibits in vivo tumor growth. (a) Effects of SFN on tumor growth of SCID mice subcutaneously inoculated with primary human CRC cell lines. The results showed that SFN 400 μM inhibited tumor growth significantly in both cancer xenografts. (b) Inhibition of tumor growth was compared among tested groups. The inhibitory ratio was normalized to the negative control (PBS group) (values represent percent of control, n = 3 *P < 0.05 versus PBS group).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3139908&req=5

fig7: SFN inhibits in vivo tumor growth. (a) Effects of SFN on tumor growth of SCID mice subcutaneously inoculated with primary human CRC cell lines. The results showed that SFN 400 μM inhibited tumor growth significantly in both cancer xenografts. (b) Inhibition of tumor growth was compared among tested groups. The inhibitory ratio was normalized to the negative control (PBS group) (values represent percent of control, n = 3 *P < 0.05 versus PBS group).
Mentions: Macroscopic tumors were observed on day 21, after injection of SFN and PBS control groups of nude mice. After injection of SFN 400 μM in the experimental group, tumors developed slowly. After 21 days of injection of SFN, no mice had died in the three groups, and the tumors were resected and measured. Small pale tumor nodules were observed in the tumors, whereas red and hypervascularized large tumors were present in the PBS control and SFN 200 μM tumor cells. The average size of tumors in the experimental group (400 μM) was 52.99% (tumor image size) and 28.70% (tumor weight), much less than the average size of the PBS control (100%) (Figure 7(b)). The results indicated that SFN could decrease tumorigenesis by inhibiting neovascularization in tumors in vivo. SFN might also have inhibitory actions on surrounding tumor tissues and indirectly inhibit tumorigenesis (Figure 7(a)).

Bottom Line: In addition, treated cells showed nuclear apoptotic morphology that coincided with an activation of caspase-3, and loss of mitochondrial membrane potential (ΔΨm).Incubations at higher SFN doses (12.5 and 25 μM) resulted in cleavage of procaspase-3 and elevated caspase-2, -3, -8, and -9 activity, suggesting that the induction of apoptosis and the sulforaphane-induced mitosis delay at the lower dose are independently regulated.Daily SFN s.c. injections (400 micromol/kg/d for 3 weeks) in severe combined immunodeficient mice with primary human CRC (CP1 to CP5) s.c. tumors resulted in a decrease of mean tumor weight by 70% compared with vehicle-treated controls.

View Article: PubMed Central - PubMed

Affiliation: Division of Traumatology, Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan.

ABSTRACT
We have investigated the anticancer effects of the dietary isothiocyanate sulforaphane (SFN) on colorectal cancer (CRC), using primary cancer cells lines isolated from five Taiwanese colorectal cancer patients as the model for colorectal cancer. SFN-treated cells accumulated in metaphase (SFN 6.25 μM) and subG1 (SFN 12.5 and 25 μM) as determined by flow cytometry. In addition, treated cells showed nuclear apoptotic morphology that coincided with an activation of caspase-3, and loss of mitochondrial membrane potential (ΔΨm). Incubations at higher SFN doses (12.5 and 25 μM) resulted in cleavage of procaspase-3 and elevated caspase-2, -3, -8, and -9 activity, suggesting that the induction of apoptosis and the sulforaphane-induced mitosis delay at the lower dose are independently regulated. Daily SFN s.c. injections (400 micromol/kg/d for 3 weeks) in severe combined immunodeficient mice with primary human CRC (CP1 to CP5) s.c. tumors resulted in a decrease of mean tumor weight by 70% compared with vehicle-treated controls. Our findings suggest that, in addition to the known effects on cancer prevention, sulforaphane may have antitumor activity in established colorectal cancer.

No MeSH data available.


Related in: MedlinePlus