Evidence of functional ryanodine receptor involved in apoptosis of prostate cancer (LNCaP) cells

Mariot, Pascal; Prevarskaya, Natalia; Roudbaraki, Morad; Bourhis, Xuefen Le; Coppenolle, Fabien Van; Vanoverberghe, Karine; Skryma, Roman

doi:10.1002/(sici)1097-0045(20000515)43:3<205::aid-pros6>3.0.co;2-m

Cited by 58 publications

(26 citation statements)

References 50 publications

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“…It is possible that cell line differences were due to differences in RyR isoforms or their expression. LNCaP cell lines have been shown to express RyR 1 and 2, but not 3 [42]. We were unable to locate studies in the literature that identified RyR isoforms in DU-145 or PWR1E cells in any prostate cell line.…”

Section: Discussionmentioning

confidence: 95%

Receptor Activated Ca2+ Release Is Inhibited by Boric Acid in Prostate Cancer Cells

et al. 2009

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BackgroundThe global disparity in cancer incidence remains a major public health problem. We focused on prostate cancer since microscopic disease in men is common, but the incidence of clinical disease varies more than 100 fold worldwide. Ca2+ signaling is a central regulator of cell proliferation, but has received little attention in cancer prevention. We and others have reported a strong dose-dependent reduction in the incidence of prostate and lung cancer within populations exposed to boron (B) in drinking water and food; and in tumor and cell proliferation in animal and cell culture models.Methods/Principal FindingsWe examined the impact of B on Ca2+ stores using cancer and non-cancer human prostate cell lines, Ca2+ indicators Rhod-2 AM and Indo-1 AM and confocal microscopy. In DU-145 cells, inhibition of Ca2+ release was apparent following treatment with Ringers containing RyR agonists cADPR, 4CmC or caffeine and respective levels of BA (50 µM), (1, 10 µM) or (10, 20, 50,150 µM). Less aggressive LNCaP cancer cells required 20 µM BA and the non-tumor cell line PWR1E required 150 µM BA to significantly inhibit caffeine stimulated Ca2+ release. BA (10 µM) and the RyR antagonist dantroline (10 µM) were equivalent in their ability to inhibit ER Ca2+ loss. Flow cytometry and confocal microscopy analysis showed exposure of DU-145 cells to 50 µM BA for 1 hr decreased stored [Ca2+] by 32%.Conclusion/SignificanceWe show B causes a dose dependent decrease of Ca2+ release from ryanodine receptor sensitive stores. This occurred at BA concentrations present in blood of geographically disparate populations. Our results suggest higher BA blood levels lower the risk of prostate cancer by reducing intracellular Ca2+ signals and storage.

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Section: Discussionmentioning

confidence: 95%

Receptor Activated Ca2+ Release Is Inhibited by Boric Acid in Prostate Cancer Cells

et al. 2009

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“…The remaining 54 mutations were categorized as missense, thus it is unknown if they are inactivating. The RYR2 gene codes for a large calcium channel and inhibition of its function protects cells against apoptosis,30 thereby promoting growth. Thus, these mutations in RYR2 may affect the cells from going into an apoptotic state.…”

Section: Discussionmentioning

confidence: 99%

Mutation analysis of adenomas and carcinomas of the colon: Early and late drivers

Wolff

Hoffman

Wolff

et al. 2018

Genes Chromosomes & Cancer

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Colorectal cancer (CRC) accounts for about 8% of all new cancer cases diagnosed in the US. We used whole exome sequence data from triplet samples (colon carcinoma, colon adenoma, and normal tissue) from 18 individuals to assess gene mutation rates. Of the 2 204 genes that were mutated, APC, TTN, TP53, KRAS, OBSCN, SOX9, PCDH17, SIGLEC10, MYH6, and BRD9 were consistent with genes being an early driver of carcinogenesis, in that they were mutated in multiple adenomas and multiple carcinomas. Fifty‐two genes were mutated in ≥12.5% of microsatellite stable (MSS) carcinomas but not in any of the adenomas, in line with the profile of a late driver event involved in tumor progression. Thirty‐eight genes were sequenced in a larger independent set of 148 carcinoma/normal tissue pairs to obtain more precise mutation frequencies. Eight of the genes, APC, TP53, ATM, CSMD3, LRP1B, RYR2, BIRC6, and MUC17, contained mutations in >20% of the carcinomas. Interestingly, mutations in four genes in addition to APC that are associated with dysregulation of Wnt signaling, were all classified as early driver events. Most of the genes that are commonly associated with colon cancer, including APC, TP53, and KRAS, were all classified as being early driver genes being mutated in both adenomas and carcinomas. Classifying genes as potential early and late driver events points to candidate genes that may help dissect pathways involved in both tumor initiation and progression.

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“…Xestospongin B as a specific IP 3 R inhibitor has been demonstrated to reduce proliferation and colony formation ability, while induce necrotic death, specifically in tumorigenic breast cells, compared with non-tumorigenic cell lines 184 . Caffeine, a RyR agonist, can induce apoptosis in prostate cancer cells, while another agonist 4-chloro- m -cresol can inhibit the breast cancer cell growth 173 . Several compounds targeting NCX, such as OSW-1, showed apoptosis-induce function by causing mitochondrial Ca 2+ overload in leukemia 174 .…”

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

433

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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Evidence of functional ryanodine receptor involved in apoptosis of prostate cancer (LNCaP) cells

Cited by 58 publications

References 50 publications

Receptor Activated Ca2+ Release Is Inhibited by Boric Acid in Prostate Cancer Cells

Receptor Activated Ca2+ Release Is Inhibited by Boric Acid in Prostate Cancer Cells

Mutation analysis of adenomas and carcinomas of the colon: Early and late drivers

Targeting calcium signaling in cancer therapy

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