Equivalent anticancer activities of dietary vitamin D and calcitriol in an animal model of breast cancer: importance of mammary CYP27B1 for treatment and prevention.
Equivalent anticancer activities of dietary vitamin D and calcitriol in an animal model of breast cancer: importance of mammary CYP27B1 for treatment and prevention.
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DOI：
10.1016/j.jsbmb.2012.08.005
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发表时间：
2013-07
影响因子：
4.1
通讯作者：
Feldman, David
中科院分区：
文献类型：
--
作者：
Krishnan, Aruna V.;Swami, Srilatha;Feldman, David
骨化三醇[1，25（OH）2D 3]是维生素D的药物活性形式，在乳腺癌（BCa）细胞培养物和BCa动物模型中发挥抗增殖、促凋亡、抗炎作用和其他抗癌作用。我们的研究重点是调查膳食维生素D3与骨化三醇相比的潜在有益作用以及BCa治疗和化学预防的潜在机制。我们最近发现，膳食维生素D3在BCa异种移植模型中表现出显着的肿瘤抑制作用，与给予活性激素钙三醇引起的作用相当。在我们的研究中测试的容易实现的剂量下，膳食维生素D3表现出显著的肿瘤抑制活性，并且与骨化三醇不同，不会引起高钙血症，证明其相对安全。我们发现补充维生素D3饮食的荷瘤小鼠的循环骨化三醇升高以及肿瘤和肠道中CYP 27 B1表达增加。我们推测，膳食维生素D3补充剂诱导的循环25（OH）D升高刺激乳腺肿瘤微环境中骨化三醇的局部合成，随后的旁分泌/自分泌作用在膳食维生素D3的抗癌活性中起主要作用。我们的研究结果表明，来自肿瘤和其他肾外来源（如肠）的骨化三醇的内分泌活性可能也在介导膳食维生素D3的抗癌作用中发挥作用。因此，似乎1α-羟基化的多个位点有助于膳食维生素D3的抗癌作用。我们的数据强烈表明，膳食维生素D将有助于BCa的化学预防和治疗，因为它是一种安全，经济和容易获得的营养剂，在发挥抗癌作用方面与骨化三醇相当，至少在小鼠模型中是如此。此外，充足的维生素D营养和避免维生素D缺乏似乎对降低BCa风险很重要。这些发现证明了在BCa患者和BCa高风险女性中进行临床试验，以评估膳食维生素D3补充剂的益处。
Calcitriol [1,25(OH)2D3], the hormonally active form of vitamin D exerts anti-proliferative, pro-apoptotic, anti-inflammatory effects and other anticancer actions in breast cancer (BCa) cell cultures and animal models of BCa. Our research is focused on investigating the potential beneficial effects of dietary vitamin D3 compared to calcitriol and the underlying mechanisms in BCa treatment and chemoprevention. We recently found that dietary vitamin D3 exhibits significant tumor inhibitory effects in xenograft models of BCa that are equivalent to those elicited by the administration of the active hormone calcitriol. At the easily achievable dose tested in our studies, dietary vitamin D3 exhibited substantial tumor inhibitory activity and, unlike calcitriol, did not cause hypercalcemia demonstrating its relative safety. We found elevations in circulating calcitriol as well as increased CYP27B1 expression in the tumor and the intestine in tumor-bearing mice ingesting a vitamin D3-supplemented diet. We hypothesize that the elevation in circulating 25(OH)D induced by dietary vitamin D3 supplements stimulates local synthesis of calcitriol in the mammary tumor microenvironment and the ensuing paracrine/autocrine actions play a major role in the anticancer activity of dietary vitamin D3. Our findings suggest that the endocrine activity of calcitriol derived from tumor and other extra-renal sources such as the intestine, probably also plays a role in mediating the anticancer effects of dietary vitamin D3. Thus it appears that multiple sites of 1α-hydroxylation contribute to the anticancer effects of dietary vitamin D3. Our data strongly suggest that dietary vitamin D will be useful in the chemoprevention and treatment of BCa since it is a safe, economical and easily available nutritional agent that is equivalent to calcitriol in exerting anticancer effects, at least in mouse models. Furthermore, adequate vitamin D nutrition and avoidance of vitamin D deficiency appear to be important in reducing BCa risk. These findings warrant clinical trials in BCa patients and in women at high risk for BCa to evaluate the benefits of dietary vitamin D3 supplementation.
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影响因子：
4
作者：
Ching, Stephen;Kashinkunti, Soumya;Niehaus, Matthew D.;Zinser, Glendon M.
通讯作者：
Zinser, Glendon M.
维生素D在预防和治疗中的作用。
DOI：
10.1016/j.ecl.2010.02.011
发表时间：
2010-06
影响因子：
4.5
作者：
Krishnan AV;Trump DL;Johnson CS;Feldman D
通讯作者：
Feldman D
DOI：
10.1016/s0960-0760(03)00028-1
发表时间：
2003-02-01
影响因子：
4.1
作者：
Flanagan, L;Packman, K;Welsh, J
通讯作者：
Welsh, J
影响因子：
2.4
作者：
FAN, FS;YU, WCY
通讯作者：
YU, WCY
影响因子：
3.8
作者：
Colston, KW;Pirianov, G;Binderup, L
通讯作者：
Binderup, L