In vitro anticancer activity of hydrogen sulfide and nitric oxide alongside nickel nanoparticle and novel mutations in their genes in CRC patients

Abstract

This study was carried out to assess the impact of nickel nanoparticles (NiNPs) as well as scorpion venom on colorectal cancer (CRC) cells in the presence and/or absence of 5-fluorouracil (5-FU), hydrogen sulfide (H2S), and nitric oxide (NO) donors and to determine alterations in endothelial NO synthase (eNOS) and cystathionine γ-lyase (CSE) enzyme-producing genes in CRC patients. The IC50 of both H2S and NO donors, along with NiNPs, were determined. The CRC cells were treated for 24hrs, and the cytotoxic activities were assessed using the MTT test. Moreover, the apoptosis was determined after 24hrs and 48hrs using TUNEL assay. Furthermore, the mutations in the eNOS gene (intron 4, -786T>C and 894 G>T) and CSE gene (1364GT) were determined using direct sequencing. The IC50 values for sodium disulfide (Na2S) and sodium nitroprusside (SNP) at 24hrs treatment were found to be 5 mM and 10−6 M, respectively, while the IC50 value for 5-FU was reached after 5-days of treatment in CRC cell line. Both black and yellow scorpion venoms showed no inhibition of cell proliferation after 24hrs treatment. Furthermore, Na2S showed a significant decrease in cell proliferation and an increase in apoptosis. Moreover, a co-treatment of SNP and 5-FU resulted in inhibition of the cytotoxic effect of 5-FU, while a combination treatment of NiNPs with Na2S, SNP, and 5-FU caused highly significant cytotoxicity. Direct sequencing reveals new mutations, mainly intronic variation in eNOS gene that has not previously been described in the database. These findings indicate that H2S promotes the anticancer efficiency of 5-FU in the presence of NiNPs while NO has antiapoptotic activity in CRC cell lines.

Iron nanoparticles green-formulated by Coriandrum sativum leaf aqueous ‎extract: Investigation of its anti-liver cancer effects

“…Metallic nanoparticles also have excellent potential to inhibit DPPH. The results obtained in our study are in line with many studies in which the mutual effect has been monitored to increase the antioxidant capacities between herbs and metallic salts against DPPH [13][14][15][16]. In general, metallic nanoparticles display remarkable and extraordinary antioxidant impacts, among which the antioxidant effects of FeNPs have been well-documented.…”

“…More importantly, laboratory evidence has shown that antioxidants can highly prevent cancer [13][14][15][16].The IC50 of BHT and FeNPs were 91 and 132 µg/mL, respectively (Figure 4; Table 1).…”

“…Direct sequencing reveals new mutations, mainly P r e p r i n t intronic variation in endothelial NO synthase gene that has not previously been described in the database. These findings indicate that H2S promotes the anticancer efficiency of 5-fluorouracil in the presence of nickel nanoparticles while NO has antiapoptotic activity in colorectal cancer cell lines [16,17]. The study of Chen et al ( 2013) revealed the anti-immortalized myelogenous leukemia activities of metallic nanoparticles green-synthesized by Tsoong herb against K562 cell line in the in vitro condition.…”

“…In fact, the green synthesized metallic nanoparticles have achieved notable consideration in a variety of medicinal disciplines [9][10][11][12]. Some relevant conducted studies have shown that some nanoparticles (Especially platin, gold, and silver nanoparticles) have promising therapeutic properties accounting for their potential use as excellent alternatives to physicochemically different metal-supported nanoparticles, antibacterial, and particularly anticancer drugs (Such as Cisplatin and Azathioprine) [10][11][12][13][14][15][16][17].…”

Gasotransmitters in the tumor microenvironment: Impacts on cancer chemotherapy (Review)

“…It is clear that H 2 S, similar to other endogenous gases, has now been identified as a gasotransmitter ( 77 ). It was initially regarded as highly poisonous in the environment; however, this perception has changed as a growing number of studies have illustrated H 2 S as a cytoprotective and cardioprotective agent ( 78 , 79 ). Fig.…”