In vivo evaluation of the anticancer activity of the gemcitabine and doxorubicin combined in a nanoemulsion

Alkhatib, Mayson H.; Alshehri, Wafa S; Abdu, Faiza

doi:10.4103/jpbs.jpbs_225_17

Cited by 17 publications

(8 citation statements)

References 21 publications

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“…), GPIII: DOX group (MCF-7 cells and DOX (2 mg/Kg; i.p.) [ 85 ] once every 3 days, GPIV: CQ group (MCF-7 cells and CQ (50 mg/Kg; i.p.) [ 19 ] once every three days.…”

Section: Methodsmentioning

confidence: 99%

Tioconazole and Chloroquine Act Synergistically to Combat Doxorubicin-Induced Toxicity via Inactivation of PI3K/AKT/mTOR Signaling Mediated ROS-Dependent Apoptosis and Autophagic Flux Inhibition in MCF-7 Breast Cancer Cells

et al. 2021

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Cancer is a complex devastating disease with enormous treatment challenges, including chemo- and radiotherapeutic resistance. Combination therapy demonstrated a promising strategy to target hard-to-treat cancers and sensitize cancer cells to conventional anti-cancer drugs such as doxorubicin. This study aimed to establish molecular profiling and therapeutic efficacy assessment of chloroquine and/or tioconazole (TIC) combination with doxorubicin (DOX) as anew combination model in MCF-7 breast cancer. The drugs are tested against apoptotic/autophagic pathways and related redox status. Molecular docking revealed that chloroquine (CQ) and TIC could be potential PI3K and ATG4B pathway inhibitors. Combination therapy significantly inhibited cancer cell viability, PI3K/AkT/mTOR pathway, and tumor-supporting autophagic flux, however, induced apoptotic pathways and altered nuclear genotoxic feature. Our data revealed that the combination cocktail therapy markedly inhibited tumor proliferation marker (KI-67) and cell growth, along with the accumulation of autophagosomes and elevation of LC3-II and p62 levels indicated autophagic flux blockage and increased apoptosis. Additionally, CQ and/or TIC combination therapy with DOX exerts its activity on the redox balance of cancer cells mediated ROS-dependent apoptosis induction achieved by GPX3 suppression. Besides, Autophagy inhibition causes moderately upregulation in ATGs 5,7 redundant proteins strengthened combinations induced apoptosis, whereas inhibition of PI3K/AKT/mTOR pathway with Beclin-1 upregulation leading to cytodestructive autophagy with overcome drug resistance effectively in curing cancer. Notably, the tumor growth inhibition and various antioxidant effects were observed in vivo. These results suggest CQ and/or TIC combination with DOX could act as effective cocktail therapy targeting autophagy and PI3K/AKT/mTOR pathways in MCF-7 breast cancer cells and hence, sensitizes cancer cells to doxorubicin treatment and combat its toxicity.

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“…), GPIII: DOX group (MCF-7 cells and DOX (2 mg/Kg; i.p.) [ 85 ] once every 3 days, GPIV: CQ group (MCF-7 cells and CQ (50 mg/Kg; i.p.) [ 19 ] once every three days.…”

Section: Methodsmentioning

confidence: 99%

Tioconazole and Chloroquine Act Synergistically to Combat Doxorubicin-Induced Toxicity via Inactivation of PI3K/AKT/mTOR Signaling Mediated ROS-Dependent Apoptosis and Autophagic Flux Inhibition in MCF-7 Breast Cancer Cells

et al. 2021

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“…By binding and stabilizing microtubules, docetaxel prevents mitotic spindle assembly and thus blocks cell cycle progression in late G2-M phase (Yvon et al, 1999;Morse et al, 2005). Chemotherapy agents affect HDL metabolism in varying ways: docetaxel increases HDL and decrease TG levels in the serum of mice bearing Ehrlich tumor (Alkhatib et al, 2017), but doxorubicin decreases HDL biogenesis by reducing the expression of ABCA1 and apoA-I, while cyclophosphamide and paclitaxel show no significant effect on HDL biogenesis (Sharma et al, 2016). Although there is no study investigating the effect of docetaxel monotherapy on lipid metabolism in humans, our discovery of docetaxel as a potent promoter of HDL biogenesis (Figures 3, 5) suggests that docetaxel may be repurposed for the treatment of ASCVD.…”

Section: Discussionmentioning

confidence: 99%

Identification of Docetaxel as a Potential Drug to Promote HDL Biogenesis

2021

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Objective: Our recent studies showed that desmocollin 1 (DSC1) binds to apoA-I in order to inhibit apoA-I-mediated high density lipoprotein (HDL) biogenesis in atherosclerotic plaques. To promote HDL biogenesis in the plaque, here we search for small molecules that block apoA-I-DSC1 interactions.Approach and Results: We combined mutational and computational mapping methods to show that amino acid residues 442–539 in the mature DSC1 protein form an apoA-I binding site (AIBS). Using a crystal structure of the AIBS, we carried out virtual screening of 10 million small molecules to estimate their binding affinities to the AIBS, followed by the selection of 51 high-affinity binding molecules as potential inhibitors of apoA-I-DSC1 interactions. Among the 51, the chemotherapy drug docetaxel showed the highest potency in promoting apoA-I-mediated HDL biogenesis in primary human skin fibroblasts with the half-maximal effective concentration of 0.72 nM. In silico docking studies suggest that the taxane ring in docetaxel binds to the AIBS and that the carbon-13 sidechain of the taxane tightens/stabilizes the binding. The HDL biogenic effect of docetaxel was also observed in two predominant cell types in atherosclerosis, macrophages and smooth muscle cells. Importantly, docetaxel promoted HDL biogenesis at concentrations much lower than those required for inducing cytotoxicity.Conclusion: Determination of the AIBS in DSC1 and AIBS structure-based virtual screening allowed us to identify docetaxel as a strong HDL biogenic agent. With the remarkable potency in promoting HDL biogenesis, a chemotherapy drug docetaxel may be repurposed to enhance atheroprotective HDL functions.

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“…Doxorubicin is an effective anti-biotic and anti-tumor drug. It has been formulated for the treatment of liver and kidney carcinoma besides to breast cancer metastasis ( Alkhatib et al, 2018 ). Accordingly, these findings reported that DOX treatment resulted in inhibition of the hepatic metastasis.…”

Section: Discussionmentioning

confidence: 99%

Magnetic field potential effects on the doxorubicin therapeutic activity in Ehrlich tumor growth

Ghannam

Al-Otaibi

Alanazy

et al. 2021

Saudi Journal of Biological Sciences

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Aim Therapeutic choices for cancer patients include many combinations of therapeutic protocols. The present study aimed to investigate and discuss the combined effects of magnetic field and chemotherapy treatment on Ehrlich tumor-induced growth in Swiss albino mice. The benefits of both treatments are discussed and interpreted. Methods Fifty adult male mice were randomly divided into two groups; ten mice in the first group served as control group and forty in the second group which received a single dose IP injection of tumor fluid (0.02 Ml) to induce tumor. Ten days post injection to allow the tumor to growth, the 40 mice were sub- divided in to 4 sub-groups 10 mice pre each to introduce the treatment. Results The results indicated tumor growth inhibition regarding mean tumor volume variation (ml) presented. All treatments display tumor growth prevention effect compared to control untreated mice. Treatment with Dox + 7G (MF) exposure exhibited a significant inhibition of tumor growth than that treated alone with DOX or magnetic field; 82% inhibition for DOX + MF 7 G against 60% for 7 G , and 31% for DOX only. Optical density data show a higher values of the molar absorption coefficient for all treated groups than untreated one. The fluorescence emission spectra of Hb show an emission peaks λ em at 465, 515, and 639 nm. Hematological examination might indicate to discriminative effects to RBCs, WBCs or/and Hb for all treated groups. Moreover, treatment with Dox + 7G MF shows a proper discriminative effects than that treatment with DOX or magnetic field only. Osmotic fragility (OF) test indicates that the combination between drug and magnetic field have nontoxic effect against RBCs membrane. Conclusion Our findings support further exploration of the potential of magnetic fields in cancer therapeutics, either as adjunct or primary therapy. It may be due to enhancing the drug interaction with tumor cells which increase the therapeutic index of DOX and resulted in increased anti-tumor activity against Ehrlich tumor models. These benefits promote the use of the magnetic field in cancer with chemotherapy over the other traditional treatment agents this highly adapted manner can be used in improving the clinical treatment protocol and fights against cancer.

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In vivo evaluation of the anticancer activity of the gemcitabine and doxorubicin combined in a nanoemulsion

Cited by 17 publications

References 21 publications

Tioconazole and Chloroquine Act Synergistically to Combat Doxorubicin-Induced Toxicity via Inactivation of PI3K/AKT/mTOR Signaling Mediated ROS-Dependent Apoptosis and Autophagic Flux Inhibition in MCF-7 Breast Cancer Cells

Tioconazole and Chloroquine Act Synergistically to Combat Doxorubicin-Induced Toxicity via Inactivation of PI3K/AKT/mTOR Signaling Mediated ROS-Dependent Apoptosis and Autophagic Flux Inhibition in MCF-7 Breast Cancer Cells

Identification of Docetaxel as a Potential Drug to Promote HDL Biogenesis

Magnetic field potential effects on the doxorubicin therapeutic activity in Ehrlich tumor growth

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