NNC 55-0396, a T-type Ca2+ channel inhibitor, inhibits angiogenesis via suppression of hypoxia-inducible factor-1α signal transduction

Kim, Ki‐Hyun; Kim, Dong‐Young; Park, Ju Yeol; Jung, Hye Jin; Cho, Yong Hee; Kim, Hyoung Kyu; Han, Jin; Choi, Kang Yell; Kwon, Ho Jeong

doi:10.1007/s00109-014-1235-1

Cited by 47 publications

(45 citation statements)

References 36 publications

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“…Moreover, a mibefradil derived novel compound, NNC-55-0396, was developed to selectively target Ca 2+ channel and exhibits less inhibitory effect on cytochrome P450 3A4. This new derived mibefradil compound appears to be a promising chemotherapy drug for that it is able to effectively inhibit angiogenesis in cancer cell lines but with minimal off-target effect42, 119.…”

Section: Drugs Targeting Ca2+ Channels/transporters/pumps For Cancer mentioning

confidence: 99%

Targeting calcium signaling in cancer therapy

Cui¹,

Merritt

et al. 2017

Acta Pharmaceutica Sinica B

461

346

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The intracellular calcium ions (Ca2+) act as second messenger to regulate gene transcription, cell proliferation, migration and death. Accumulating evidences have demonstrated that intracellular Ca2+ homeostasis is altered in cancer cells and the alteration is involved in tumor initiation, angiogenesis, progression and metastasis. Targeting derailed Ca2+ signaling for cancer therapy has become an emerging research area. This review summarizes some important Ca2+ channels, transporters and Ca2+-ATPases, which have been reported to be altered in human cancer patients. It discusses the current research effort toward evaluation of the blockers, inhibitors or regulators for Ca2+ channels/transporters or Ca2+-ATPase pumps as anti-cancer drugs. This review is also aimed to stimulate interest in, and support for research into the understanding of cellular mechanisms underlying the regulation of Ca2+ signaling in different cancer cells, and to search for novel therapies to cure these malignancies by targeting Ca2+ channels or transporters.

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Section: Drugs Targeting Ca2+ Channels/transporters/pumps For Cancer mentioning

confidence: 99%

Targeting calcium signaling in cancer therapy

Cui¹,

Merritt

et al. 2017

Acta Pharmaceutica Sinica B

461

346

View full text Add to dashboard Cite

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“…Table 1 Recently discovered pro-and anti-angiogenesis factors Pro-angiogenesis TGLI1 [63], H19 [51], C/EBPbeta [14], MCSF [15], annexin A2 [39], CXCR4 [66], Oct-3/4 [16], miR-31 [50], miR-148a, HSP47 [38] Anti-angiogenesis hHSS1 [29], NNC55-0396 [30], TTAC-0001 [67], calpastatin [68], miR-137 [65], EZH2 [65], BMP7v [31], PDCD10 [32], JSI-124 [33] Brain Tumor Pathol…”

Section: Resultsmentioning

confidence: 99%

“…NNC55-0396, a T-type Ca 2? channel inhibitor, is illuminated to block angiogenesis by suppressing hypoxia-inducible factor (HIF)-1 alpha stability and synthesis [30]. As members of the TGF-beta superfamily, bone morphogenetic proteins 7 variant (BMP7v) has been demonstrated possessing the role of inhibition of neoangiogenesis and decreasing angiogenesis in GBM stem-like cells [31].…”

Section: Angiogenesis In Gbm and Anti-angiogenic Therapiesmentioning

confidence: 99%

Recent advance in molecular angiogenesis in glioblastoma: the challenge and hope for anti-angiogenic therapy

Zhang

et al. 2015

Brain Tumor Pathol

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Glioblastoma (GBM) is the most highly malignant brain tumor in the human central nerve system. In this paper, we review new and significant molecular findings on angiogenesis and possible resistance mechanisms. Expression of a number of genes and regulators has been shown to be upregulated in GBM microvessel cells, such as interleukin-8, signal transducer and activator of transcription 3, Tax-interacting protein-1, hypoxia induced factor-1 and anterior gradient protein 2. The regulator factors that may strongly promote angiogenesis by promoting endothelial cell metastasis, changing the microenvironment, enhancing the ability of resistance to anti-angiogenic therapy, and that inhibit angiogenesis are reviewed. Based on the current knowledge, several potential targets and strategies are proposed for better therapeutic outcomes, such as its mRNA interference of DII4-Notch signaling pathway and depletion of b1 integrin expression. We also discuss possible mechanisms underlying the resistance to anti-angiogenesis and future directions and challenges in developing new targeted therapy for GBM.

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“…Indeed, there is a consensus that carcinogenesis process is associated with an increased expression, or abnormal activation, of Ca 2+ channels, Ca 2+ transporters or Ca 2+ -ATPases [2], making these structures therapeutic targets for inhibiting cancer growth. For example, this issue can be observed by the use of selective SERCA pump inhibitor, thapsigargin [7]; Ca 2+ channel blockers (CCBs), such as amlodipine and mibefradil used in anti-hypertensive therapy [8,9]; and also a mibefradil derived novel compound, named NNC-55-0396 [10]; CICRs and TRP channel regulators; the imidazole compound, named SKF 96365; and related antimycotic compounds, including econazole, miconazole and clotrimazole [11].…”

Section: Introductionmentioning

confidence: 99%