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Repurposing vitamin D for treatment of human malignancies via targeting tumor microenvironment.

ABSTRACT: Tumor cells along with a small proportion of cancer stem cells exist in a stromal microenvironment consisting of vasculature, cancer-associated fibroblasts, immune cells and extracellular components. Recent epidemiological and clinical studies strongly support that vitamin D supplementation is associated with reduced cancer risk and favorable prognosis. Experimental results suggest that vitamin D not only suppresses cancer cells, but also regulates tumor microenvironment to facilitate tumor repression. In this review, we have outlined the current knowledge on epidemiological studies and clinical trials of vitamin D. Notably, we summarized and discussed the anticancer action of vitamin D in cancer cells, cancer stem cells and stroma cells in tumor microenvironment, providing a better understanding of the role of vitamin D in cancer. We presently re-propose vitamin D to be a novel and economical anticancer agent.

SUBMITTER: Wu X

PROVIDER: S-EPMC6437556 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Repurposing vitamin D for treatment of human malignancies <i>via</i> targeting tumor microenvironment.

Wu Xu X Hu Wei W Lu Lan L Zhao Yueshui Y Zhou Yejiang Y Xiao Zhangang Z Zhang Lin L Zhang Hanyu H Li Xiaobing X Li Wanping W Wang Shengpeng S Cho Chi Hin CH Shen Jing J Li Mingxing M

Acta pharmaceutica Sinica. B 20180906 2

Tumor cells along with a small proportion of cancer stem cells exist in a stromal microenvironment consisting of vasculature, cancer-associated fibroblasts, immune cells and extracellular components. Recent epidemiological and clinical studies strongly support that vitamin D supplementation is associated with reduced cancer risk and favorable prognosis. Experimental results suggest that vitamin D not only suppresses cancer cells, but also regulates tumor microenvironment to facilitate tumor repr ...[more]

PMID: 30972274

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Project description:BackgroundX-Ray induced phototherapy is highly sought after as it provides a deep tissue, synergistic method of treating cancers via standard-of-care radiotherapy. When this is combined with releasable chemotherapy agents, it can provide high target selectivity, with reduced off-target organ effects that limit current systemic therapies. We have recently developed a unique light-activated drug delivery system whereby the drug is conjugated to an alkylcobalamin scaffold. Alkylcobalamins are actively transported into cells by transcobalamin receptors (TCblR), which are overexpressed in a variety of cancer types. We hope to utilize this cobalamin scaffold technology for drug delivery in pancreatic adenocarcinoma (PDAC) cancer.MethodsThe ability of the cobalamin scaffold to selectively target PDAC was investigated by treating mice that had MIA PaCa-2 xenografts with an alkylcobalamin labeled with the fluorophore Bodipy650 (Bodipy650-cobalamin). The mice were imaged alive and organs as well as tumors were subsequently imaged ex vivo. In addition, we examined the potential of the cobalamin scaffold to deliver drugs to orthotopic pancreas MIA PaCa-2 tumors with Bodipy650-cobalamin. We determined the light dose required for release of cargo from the cobalamin scaffold by examining the fluorescence increase of Bodipy650-cobalamin in response to red light (650 nm). Finally, we probed the ability of the cobalamin scaffold to release cargo with increasing X-ray doses from a clinical linear accelerator.ResultsWe have found that Bodipy650-cobalamin was shown to localize in MIA PaCa-2 tumors, both in flank and orthotopic models. We quantified a light dose for red light release from the cobalamin scaffold that is within normal clinical doses required for photodynamic therapy. This derivative was also activated with clinical X-ray doses from a linear accelerator.ConclusionsTumor selectivity combined with fluorescence detection demonstrates the effectiveness of the vitamin B12 scaffold as a theranostic targeting agent. The activation of this scaffold with radiation from a linear accelerator shows potential for action as radiation-induced chemotherapy.

Dataset Information

Repurposing vitamin D for treatment of human malignancies via targeting tumor microenvironment.

Publications

Repurposing vitamin D for treatment of human malignancies <i>via</i> targeting tumor microenvironment.

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