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Mechanical stress promotes cisplatin-induced hepatocellular carcinoma cell death.

Ziko L, Riad S, Amer M, Zdero R, Bougherara H, Amleh A - Biomed Res Int (2015)

Bottom Line: Our results demonstrated that mechanical stress promoted CisPt-induced death of HepG2 cells (~35% more cell death).Moreover, results showed that CisPt-induced death was compromised when CisPt was left to mix with carnosine 24 hours preceding treatment.Mechanical stress, however, ameliorated cell death (20% more cell death).

View Article: PubMed Central - PubMed

Affiliation: Biotechnology Program, School of Sciences and Engineering, The American University in Cairo, AUC Avenue, New Cairo 11835, Egypt.

ABSTRACT
Cisplatin (CisPt) is a commonly used platinum-based chemotherapeutic agent. Its efficacy is limited due to drug resistance and multiple side effects, thereby warranting a new approach to improving the pharmacological effect of CisPt. A newly developed mathematical hypothesis suggested that mechanical loading, when coupled with a chemotherapeutic drug such as CisPt and immune cells, would boost tumor cell death. The current study investigated the aforementioned mathematical hypothesis by exposing human hepatocellular liver carcinoma (HepG2) cells to CisPt, peripheral blood mononuclear cells, and mechanical stress individually and in combination. HepG2 cells were also treated with a mixture of CisPt and carnosine with and without mechanical stress to examine one possible mechanism employed by mechanical stress to enhance CisPt effects. Carnosine is a dipeptide that reportedly sequesters platinum-based drugs away from their pharmacological target-site. Mechanical stress was achieved using an orbital shaker that produced 300 rpm with a horizontal circular motion. Our results demonstrated that mechanical stress promoted CisPt-induced death of HepG2 cells (~35% more cell death). Moreover, results showed that CisPt-induced death was compromised when CisPt was left to mix with carnosine 24 hours preceding treatment. Mechanical stress, however, ameliorated cell death (20% more cell death).

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Related in: MedlinePlus

Different carnosine : CisPt molar ratios cytotoxic effect on HepG2 cells for 24 hours as per MTT assay. The data are presented as a mean of at least three independent experiments (mean ± SD). Left to right: Media = control HepG2 cells. Car : Cis 1 : 1 = HepG2 cells exposed to CisPt 8 μg/mL and carnosine in 1 : 1 molar ratio. Car : Cis 1.5 : 1 = HepG2 cells exposed to CisPt 8 μg/mL and carnosine in 1.5 : 1 molar ratio. Car : Cis 2 : 1 = HepG2 cells exposed to CisPt 8 μg/mL and carnosine in 2 : 1 molar ratio. Car : Cis 2.5 : 1 = HepG2 cells exposed to CisPt 8 μg/mL and carnosine in 2.5 : 1 molar ratio. Car : Cis 3 : 1 = HepG2 cells exposed to CisPt 8 μg/mL and carnosine in 3 : 1 molar ratio (error bars represent the standard deviation). The P values shown are the values of the mean of every condition as compared to the control cells (***P < 0.001).
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fig5: Different carnosine : CisPt molar ratios cytotoxic effect on HepG2 cells for 24 hours as per MTT assay. The data are presented as a mean of at least three independent experiments (mean ± SD). Left to right: Media = control HepG2 cells. Car : Cis 1 : 1 = HepG2 cells exposed to CisPt 8 μg/mL and carnosine in 1 : 1 molar ratio. Car : Cis 1.5 : 1 = HepG2 cells exposed to CisPt 8 μg/mL and carnosine in 1.5 : 1 molar ratio. Car : Cis 2 : 1 = HepG2 cells exposed to CisPt 8 μg/mL and carnosine in 2 : 1 molar ratio. Car : Cis 2.5 : 1 = HepG2 cells exposed to CisPt 8 μg/mL and carnosine in 2.5 : 1 molar ratio. Car : Cis 3 : 1 = HepG2 cells exposed to CisPt 8 μg/mL and carnosine in 3 : 1 molar ratio (error bars represent the standard deviation). The P values shown are the values of the mean of every condition as compared to the control cells (***P < 0.001).

Mentions: Fourth, for cell viability % versus carnosine : cisplatin ratio (Figure 5), the raw data were initially corrected by comparison to blank readings. The corrected data were then analyzed using a one-way ANOVA with Tukey's HSD test (P < 0.001) for pair-wise comparisons. Tukey's method was used, because the Levene test showed homogeneity of variances between groups (P = 0.227).


Mechanical stress promotes cisplatin-induced hepatocellular carcinoma cell death.

Ziko L, Riad S, Amer M, Zdero R, Bougherara H, Amleh A - Biomed Res Int (2015)

Different carnosine : CisPt molar ratios cytotoxic effect on HepG2 cells for 24 hours as per MTT assay. The data are presented as a mean of at least three independent experiments (mean ± SD). Left to right: Media = control HepG2 cells. Car : Cis 1 : 1 = HepG2 cells exposed to CisPt 8 μg/mL and carnosine in 1 : 1 molar ratio. Car : Cis 1.5 : 1 = HepG2 cells exposed to CisPt 8 μg/mL and carnosine in 1.5 : 1 molar ratio. Car : Cis 2 : 1 = HepG2 cells exposed to CisPt 8 μg/mL and carnosine in 2 : 1 molar ratio. Car : Cis 2.5 : 1 = HepG2 cells exposed to CisPt 8 μg/mL and carnosine in 2.5 : 1 molar ratio. Car : Cis 3 : 1 = HepG2 cells exposed to CisPt 8 μg/mL and carnosine in 3 : 1 molar ratio (error bars represent the standard deviation). The P values shown are the values of the mean of every condition as compared to the control cells (***P < 0.001).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4317602&req=5

fig5: Different carnosine : CisPt molar ratios cytotoxic effect on HepG2 cells for 24 hours as per MTT assay. The data are presented as a mean of at least three independent experiments (mean ± SD). Left to right: Media = control HepG2 cells. Car : Cis 1 : 1 = HepG2 cells exposed to CisPt 8 μg/mL and carnosine in 1 : 1 molar ratio. Car : Cis 1.5 : 1 = HepG2 cells exposed to CisPt 8 μg/mL and carnosine in 1.5 : 1 molar ratio. Car : Cis 2 : 1 = HepG2 cells exposed to CisPt 8 μg/mL and carnosine in 2 : 1 molar ratio. Car : Cis 2.5 : 1 = HepG2 cells exposed to CisPt 8 μg/mL and carnosine in 2.5 : 1 molar ratio. Car : Cis 3 : 1 = HepG2 cells exposed to CisPt 8 μg/mL and carnosine in 3 : 1 molar ratio (error bars represent the standard deviation). The P values shown are the values of the mean of every condition as compared to the control cells (***P < 0.001).
Mentions: Fourth, for cell viability % versus carnosine : cisplatin ratio (Figure 5), the raw data were initially corrected by comparison to blank readings. The corrected data were then analyzed using a one-way ANOVA with Tukey's HSD test (P < 0.001) for pair-wise comparisons. Tukey's method was used, because the Levene test showed homogeneity of variances between groups (P = 0.227).

Bottom Line: Our results demonstrated that mechanical stress promoted CisPt-induced death of HepG2 cells (~35% more cell death).Moreover, results showed that CisPt-induced death was compromised when CisPt was left to mix with carnosine 24 hours preceding treatment.Mechanical stress, however, ameliorated cell death (20% more cell death).

View Article: PubMed Central - PubMed

Affiliation: Biotechnology Program, School of Sciences and Engineering, The American University in Cairo, AUC Avenue, New Cairo 11835, Egypt.

ABSTRACT
Cisplatin (CisPt) is a commonly used platinum-based chemotherapeutic agent. Its efficacy is limited due to drug resistance and multiple side effects, thereby warranting a new approach to improving the pharmacological effect of CisPt. A newly developed mathematical hypothesis suggested that mechanical loading, when coupled with a chemotherapeutic drug such as CisPt and immune cells, would boost tumor cell death. The current study investigated the aforementioned mathematical hypothesis by exposing human hepatocellular liver carcinoma (HepG2) cells to CisPt, peripheral blood mononuclear cells, and mechanical stress individually and in combination. HepG2 cells were also treated with a mixture of CisPt and carnosine with and without mechanical stress to examine one possible mechanism employed by mechanical stress to enhance CisPt effects. Carnosine is a dipeptide that reportedly sequesters platinum-based drugs away from their pharmacological target-site. Mechanical stress was achieved using an orbital shaker that produced 300 rpm with a horizontal circular motion. Our results demonstrated that mechanical stress promoted CisPt-induced death of HepG2 cells (~35% more cell death). Moreover, results showed that CisPt-induced death was compromised when CisPt was left to mix with carnosine 24 hours preceding treatment. Mechanical stress, however, ameliorated cell death (20% more cell death).

Show MeSH
Related in: MedlinePlus