[Pt(O,O'-acac)(γ-acac)(DMS)]: Alternative Strategies to Overcome Cisplatin-Induced Side Effects and Resistance in T98G Glioma Cells

Astesana, Valentina; Faris, Pawan; Ferrari, Béatrice; Siciliani, Stella; Lim, Dmitry; Biggiogera, Marco; Pascali, Sandra Angelica De; Fanizzi, Francesco Paolo; Roda, Elisa; Moccia, Francesco; Bottone, Maria Grazia

doi:10.1007/s10571-020-00873-8

Cited by 14 publications

(11 citation statements)

References 85 publications

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“…Notably, a significant percentage of mCRC cells was found to be in late apoptosis under control conditions and exposure to 100 µM NaHS did not exacerbate the extent of mCRC cell death ( Figure 13 C,D). Depolarization of mitochondrial potential (ΔΨ m ) is regarded an widespread early marker of apoptosis [ 65 , 66 ]. Consistent with previous findings, exposure to 100 µM NaHS for 72 h did not significantly change in ΔΨ m mCRC cells loaded with tetramethylrhodamine, methyl ester (TMRM) ( Figure 13 E).…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, the Ca 2+ response evoked by exogenous administration of H 2 S displayed transient kinetics in the majority of mCRC cells. Conversely, pro-apoptotic Ca 2+ signals usually consist in prolonged elevations in [Ca 2+ ] i , which persist as long as the stimulus is presented to the cells [ 66 , 106 , 107 , 108 , 109 ], as we have recently shown in cisplatin-treated glioblastoma cells [ 65 ].…”

Section: Discussionmentioning

confidence: 99%

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Hydrogen Sulfide-Evoked Intracellular Ca2+ Signals in Primary Cultures of Metastatic Colorectal Cancer Cells

Faris

Ferulli

Vismara

et al. 2020

Cancers

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Exogenous administration of hydrogen sulfide (H2S) is emerging as an alternative anticancer treatment. H2S-releasing compounds have been shown to exert a strong anticancer effect by suppressing proliferation and/or inducing apoptosis in several cancer cell types, including colorectal carcinoma (CRC). The mechanism whereby exogenous H2S affects CRC cell proliferation is yet to be clearly elucidated, but it could involve an increase in intracellular Ca2+ concentration ([Ca2+]i). Herein, we sought to assess for the first time whether (and how) sodium hydrosulfide (NaHS), one of the most widely employed H2S donors, induced intracellular Ca2+ signals in primary cultures of human metastatic CRC (mCRC) cells. We provided the evidence that NaHS induced extracellular Ca2+ entry in mCRC cells by activating the Ca2+-permeable channel Transient Receptor Potential Vanilloid 1 (TRPV1) followed by the Na+-dependent recruitment of the reverse-mode of the Na+/Ca2+ (NCX) exchanger. In agreement with these observations, TRPV1 protein was expressed and capsaicin, a selective TRPV1 agonist, induced Ca2+ influx by engaging both TRPV1 and NCX in mCRC cells. Finally, NaHS reduced mCRC cell proliferation, but did not promote apoptosis or aberrant mitochondrial depolarization. These data support the notion that exogenous administration of H2S may prevent mCRC cell proliferation through an increase in [Ca2+]i, which is triggered by TRPV1.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hydrogen Sulfide-Evoked Intracellular Ca2+ Signals in Primary Cultures of Metastatic Colorectal Cancer Cells

Faris

Ferulli

Vismara

et al. 2020

Cancers

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“…Ratio measurements were performed and plotted online every 3 s. The experiments were performed at room temperature (22 °C). Resting [Ca 2+ ] i in the three cell types was monitored by using the Grynkiewicz method, as described in [ 35 ].…”

Section: Methodsmentioning

confidence: 99%

Store-Operated Ca2+ Entry Is Up-Regulated in Tumour-Infiltrating Lymphocytes from Metastatic Colorectal Cancer Patients

Faris

Rumolo

Tapella

et al. 2022

Cancers

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(1) Background: Store-operated Ca2+ entry (SOCE) drives the cytotoxic activity of cytotoxic T lymphocytes (CTLs) against cancer cells. However, SOCE can be enhanced in cancer cells due to an increase in the expression and/or function of its underlying molecular components, i.e., STIM1 and Orai1. Herein, we evaluated the SOCE expression and function in tumour-infiltrating lymphocytes (TILs) from metastatic colorectal cancer (mCRC) patients. (2) Methods: Functional studies were conducted in TILs expanded ex vivo from CRC liver metastases. Peripheral blood T cells from healthy donors (hPBTs) and mCRC patients (cPBTs) were used as controls. (3) Results: SOCE amplitude is enhanced in TILs compared to hPBTs and cPBTs, but the STIM1 protein is only up-regulated in TILs. Pharmacological manipulation showed that the increase in SOCE mainly depends on tonic modulation by diacylglycerol kinase, which prevents the protein kinase C-dependent inhibition of SOCE activity. The larger SOCE caused a stronger Ca2+ response to T-cell receptor stimulation by autologous mCRC cells. Reducing Ca2+ influx with BTP-2 during target cell killing significantly increases cytotoxic activity at low target:effector ratios. (4) Conclusions: SOCE is enhanced in ex vivo-expanded TILs deriving from mCRC patients but decreasing Ca2+ influx with BTP-2 increases cytotoxic activity at a low TIL density.

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“…Cells were excited at 340 and 380 nm and the light emitted was revealed at 510 nm. The calibration of resting intracellular Ca 2+ levels was done using Grynkiewicz, as shown in [ 18 ]. UTP (100 μM) was added for 5 min, in absence of external calcium (0 Ca 2+ ), to stimulate calcium release from ER through the IP 3 R channel.…”

Section: Methodsmentioning

confidence: 99%

Knocking out TMEM38B in human foetal osteoblasts hFOB 1.19 by CRISPR/Cas9: A model for recessive OI type XIV

et al. 2021

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Osteogenesis imperfecta (OI) type XIV is a rare recessive bone disorder characterized by variable degree of severity associated to osteopenia. It is caused by mutations in TMEM38B encoding for the trimeric intracellular cation channel TRIC-B, specific for potassium and ubiquitously present in the endoplasmic reticulum (ER) membrane. OI type XIV molecular basis is largely unknown and, due to the rarity of the disease, the availability of patients’ osteoblasts is challenging. Thus, CRISPR/Cas9 was used to knock out (KO) TMEM38B in the human Foetal Osteoblast hFOB 1.19 to obtain an OI type XIV model. CRISPR/Cas9 is a powerful technology to generate in vitro and in vivo models for heritable disorders. Its limited cost and ease of use make this technique widely applicable in most laboratories. Nevertheless, to fully take advantage of this approach, it is important to be aware of its strengths and limitations. Three gRNAs were used and several KO clones lacking the expression of TRIC-B were obtained. Few clones were validated as good models for the disease since they reproduce the altered ER calcium flux, collagen I structure and impaired secretion and osteoblastic markers expression detected in patients’ cells. Impaired proliferation and mineralization in KO clones unveiled the relevance of TRIC-B in osteoblasts functionality.

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[Pt(O,O'-acac)(γ-acac)(DMS)]: Alternative Strategies to Overcome Cisplatin-Induced Side Effects and Resistance in T98G Glioma Cells

Cited by 14 publications

References 85 publications

Hydrogen Sulfide-Evoked Intracellular Ca2+ Signals in Primary Cultures of Metastatic Colorectal Cancer Cells

Hydrogen Sulfide-Evoked Intracellular Ca2+ Signals in Primary Cultures of Metastatic Colorectal Cancer Cells

Store-Operated Ca2+ Entry Is Up-Regulated in Tumour-Infiltrating Lymphocytes from Metastatic Colorectal Cancer Patients

Knocking out TMEM38B in human foetal osteoblasts hFOB 1.19 by CRISPR/Cas9: A model for recessive OI type XIV

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