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Menthol Enhances an Antiproliferative Activity of 1alpha,25-Dihydroxyvitamin D(3) in LNCaP Cells.

Park EJ, Kim SH, Kim BJ, Kim SY, So I, Jeon JH - J Clin Biochem Nutr (2009)

Bottom Line: We found that menthol per se does not exhibit antiproliferative activity, but it is able to enhance 1alpha,25(OH)(2)D(3)-mediated growth inhibition in LNCaP cells.Fluorometric assays using Fura-2 showed that 1alpha,25(OH)(2)D(3) does not induce acute Ca(2+) response, whereas menthol evokes an increase in [Ca(2+)](i), which suggests that cross-talks of menthol-induced Ca(2+) signaling with 1alpha,25(OH)(2)D(3)-mediated growth inhibition pathways.Thus, our findings suggest that menthol may be a useful natural compound to enhance therapeutic effects of 1alpha,25(OH)(2)D(3).

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Seoul National University College of Medicine, Seoul 110-799, Korea.

ABSTRACT
1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)], the most active form of vitamin D(3), and its analogues have therapeutic benefits for prostate cancer treatment. However, the development of hypercalcemia is an obstacle to clinical applications of 1alpha,25(OH)(2)D(3) for cancer therapy. In this study, we provide evidence that menthol, a key component of peppermint oil, increases an anti-proliferation activity of 1alpha,25(OH)(2)D(3) in LNCaP prostate cancer cells. We found that menthol per se does not exhibit antiproliferative activity, but it is able to enhance 1alpha,25(OH)(2)D(3)-mediated growth inhibition in LNCaP cells. Fluorometric assays using Fura-2 showed that 1alpha,25(OH)(2)D(3) does not induce acute Ca(2+) response, whereas menthol evokes an increase in [Ca(2+)](i), which suggests that cross-talks of menthol-induced Ca(2+) signaling with 1alpha,25(OH)(2)D(3)-mediated growth inhibition pathways. In addition, Western blot analysis revealed that 1alpha,25(OH)(2)D(3) and menthol cooperatively modulate the expression of bcl-2 and p21 which provides the insight into the molecular mechanisms underlying the enhanced 1alpha,25(OH)(2)D(3)-mediated growth inhibition by menthol. Thus, our findings suggest that menthol may be a useful natural compound to enhance therapeutic effects of 1alpha,25(OH)(2)D(3).

No MeSH data available.


Related in: MedlinePlus

The expression of apoptosis- or cell cycle-related genes in LNCaP cells exposed to 10−4 mM 1α,25(OH)2D3 and 0.8 mM menthol. Western blot analyses of proteins following treatment with 1α,25(OH)2D3 and menthol for 72 h. Data shown are a representative result of at least four independent experiments. GAPDH was used as a loading control.
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Figure 3: The expression of apoptosis- or cell cycle-related genes in LNCaP cells exposed to 10−4 mM 1α,25(OH)2D3 and 0.8 mM menthol. Western blot analyses of proteins following treatment with 1α,25(OH)2D3 and menthol for 72 h. Data shown are a representative result of at least four independent experiments. GAPDH was used as a loading control.

Mentions: To get a clue to the molecular mechanisms underlying the enhanced antiproliferation effect of the combination of 1α,25(OH)2D3 with menthol, we performed Western blot analyses with LNCaP cells. Neither caspase-3 nor PARP, a caspase-3 substrate, was cleaved in the experimental conditions used (Fig. 3A) which indicates that 1α,25(OH)2D3 plus menthol does not induce caspase-3-dependent apoptosis. We then examined the expression levels of an anti-apoptotic gene bcl-2 and cell cycle inhibitors p21 and p27. The expression of bcl-2 was markedly reduced by the combined treatment of 1α,25(OH)2D3 with menthol, which may permit the cells to be vulnerable to apoptotic stimuli. The expression level of bcl-2 appeared to be unaffected by either alone (Fig. 3B). However, of five independent experiments, we once observed the reduced expression of bcl-2 by 1α,25(OH)2D3 alone but not by menthol alone. The expression of p21 was reduced by treatment with either alone, but the reduction of p21 was more remarkable when 1α,25(OH)2D3 was combined with menthol (Fig. 3B). The expression of p27 was not affected by 1α,25(OH)2D3 or menthol, either alone or in combination (Fig. 3B).


Menthol Enhances an Antiproliferative Activity of 1alpha,25-Dihydroxyvitamin D(3) in LNCaP Cells.

Park EJ, Kim SH, Kim BJ, Kim SY, So I, Jeon JH - J Clin Biochem Nutr (2009)

The expression of apoptosis- or cell cycle-related genes in LNCaP cells exposed to 10−4 mM 1α,25(OH)2D3 and 0.8 mM menthol. Western blot analyses of proteins following treatment with 1α,25(OH)2D3 and menthol for 72 h. Data shown are a representative result of at least four independent experiments. GAPDH was used as a loading control.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2654468&req=5

Figure 3: The expression of apoptosis- or cell cycle-related genes in LNCaP cells exposed to 10−4 mM 1α,25(OH)2D3 and 0.8 mM menthol. Western blot analyses of proteins following treatment with 1α,25(OH)2D3 and menthol for 72 h. Data shown are a representative result of at least four independent experiments. GAPDH was used as a loading control.
Mentions: To get a clue to the molecular mechanisms underlying the enhanced antiproliferation effect of the combination of 1α,25(OH)2D3 with menthol, we performed Western blot analyses with LNCaP cells. Neither caspase-3 nor PARP, a caspase-3 substrate, was cleaved in the experimental conditions used (Fig. 3A) which indicates that 1α,25(OH)2D3 plus menthol does not induce caspase-3-dependent apoptosis. We then examined the expression levels of an anti-apoptotic gene bcl-2 and cell cycle inhibitors p21 and p27. The expression of bcl-2 was markedly reduced by the combined treatment of 1α,25(OH)2D3 with menthol, which may permit the cells to be vulnerable to apoptotic stimuli. The expression level of bcl-2 appeared to be unaffected by either alone (Fig. 3B). However, of five independent experiments, we once observed the reduced expression of bcl-2 by 1α,25(OH)2D3 alone but not by menthol alone. The expression of p21 was reduced by treatment with either alone, but the reduction of p21 was more remarkable when 1α,25(OH)2D3 was combined with menthol (Fig. 3B). The expression of p27 was not affected by 1α,25(OH)2D3 or menthol, either alone or in combination (Fig. 3B).

Bottom Line: We found that menthol per se does not exhibit antiproliferative activity, but it is able to enhance 1alpha,25(OH)(2)D(3)-mediated growth inhibition in LNCaP cells.Fluorometric assays using Fura-2 showed that 1alpha,25(OH)(2)D(3) does not induce acute Ca(2+) response, whereas menthol evokes an increase in [Ca(2+)](i), which suggests that cross-talks of menthol-induced Ca(2+) signaling with 1alpha,25(OH)(2)D(3)-mediated growth inhibition pathways.Thus, our findings suggest that menthol may be a useful natural compound to enhance therapeutic effects of 1alpha,25(OH)(2)D(3).

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Seoul National University College of Medicine, Seoul 110-799, Korea.

ABSTRACT
1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)], the most active form of vitamin D(3), and its analogues have therapeutic benefits for prostate cancer treatment. However, the development of hypercalcemia is an obstacle to clinical applications of 1alpha,25(OH)(2)D(3) for cancer therapy. In this study, we provide evidence that menthol, a key component of peppermint oil, increases an anti-proliferation activity of 1alpha,25(OH)(2)D(3) in LNCaP prostate cancer cells. We found that menthol per se does not exhibit antiproliferative activity, but it is able to enhance 1alpha,25(OH)(2)D(3)-mediated growth inhibition in LNCaP cells. Fluorometric assays using Fura-2 showed that 1alpha,25(OH)(2)D(3) does not induce acute Ca(2+) response, whereas menthol evokes an increase in [Ca(2+)](i), which suggests that cross-talks of menthol-induced Ca(2+) signaling with 1alpha,25(OH)(2)D(3)-mediated growth inhibition pathways. In addition, Western blot analysis revealed that 1alpha,25(OH)(2)D(3) and menthol cooperatively modulate the expression of bcl-2 and p21 which provides the insight into the molecular mechanisms underlying the enhanced 1alpha,25(OH)(2)D(3)-mediated growth inhibition by menthol. Thus, our findings suggest that menthol may be a useful natural compound to enhance therapeutic effects of 1alpha,25(OH)(2)D(3).

No MeSH data available.


Related in: MedlinePlus