The synergistic effect between vanillin and doxorubicin in ehrlich ascites carcinoma solid tumor and MCF-7 human breast cancer cell line

Elsherbiny, Nehal M.; Younis, Naveed; Shaheen, Mohamed A.; Elseweidy, Mohamed M.

doi:10.1016/j.prp.2016.06.004

Cited by 50 publications

(45 citation statements)

References 30 publications

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“…Meanwhile, pre-treatment with vanillin in this study reduced gastric levels of TBARs and increased GSH level, SOD and CAT activities indicating a decrement in the indomethacin induced oxidative stress and this was superior to ranitidine pre-treatment. These findings are in harmony with earlier reports who noted the antioxidant property of vanillin [20][21][22][23].…”

Section: Discussionsupporting

confidence: 92%

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Gastroprotective Effect of Vanillin on Indomethacin-Induced Gastric Ulcer in Rats: Protective Pathways and Anti-Secretory Mechanism

Ma¹,

Salahuddin²

2017

Clin Exp Pharmacol

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Indomethacin provokes aggressive ulcerogenic adverse effects. Natural products with fewer side effects are therefore highly requested to attenuate its gastric ulcer effect. Vanillin is a natural compound widely used as flavoring agent which has antioxidant activity. Therefore, the aim of this study was to investigate its gastroprotective effect against indomethacin induced gastric injury. Rats were divided into four groups; first group served as control, group 2: Treated with indomethacin (25 mg/kg, po.), group 3: Pre-treated with ranitidine (reference drug) (50 mg/kg, po., 5 days) before indomethacin and group 4: Pretreated with vanillin (100 mg/kg, po., 5 days). Pre-treatment with vanillin reduced ulcer index, gastric juice volume, free, total acidity and histopathological changes induced by indomethacin. Although it reduced gastric oxidative stress, it elevated enzymatic antioxidant activity and gastric nitric oxide content. Moreover, it reduced gastric NFκB protein expression and activity as well as inhibition in levels of proinflammatory cytokines, Myeloperoxidase (MPO) and caspase 3 activities. It down regulated gene expression of TNF-α, Cytokine-Induced Neutrophil Chemo Attractant (CINC-2α) and caspase-9 while lacking effect on mucosal prostaglandin E2 (PGE2) level. Collectively, vanillin displayed gastroprotective effects in indomethacin induced gastric ulcer by anti-secretory action and cytoprotective effect via antioxidant and anti-inflammatory activities.

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Section: Discussionsupporting

confidence: 92%

“…Previous studies also noted vanillin's anti-inflammatory property [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32]. Moreover it was proved that also vanillic acid regulated ulcerative colitis via inhibition NF-κB p65 activation and reduction in pro-inflammatory cytokines production; IL-1, IL-6 and TNF-α [33].…”

Section: Discussionmentioning

confidence: 94%

Gastroprotective Effect of Vanillin on Indomethacin-Induced Gastric Ulcer in Rats: Protective Pathways and Anti-Secretory Mechanism

Ma¹,

Salahuddin²

2017

Clin Exp Pharmacol

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“…[ 18,13,19 ] We reported antineoplastic activity of vanillin in vivo in mouse model of breast cancer and in MCF‐7 human breast cancer cell line. [ 20 ] Vanillin exerted antineoplastic effect similar to that of doxorubicin with improved survival and no side effects as seen in doxorubicin treatment. The combination of doxorubicin and vanillin significantly inhibited tumour growth in vivo and in MCF‐7 human breast cancer cell line more than any single drug.…”

Section: Introductionmentioning

confidence: 99%

Modulation of NADPH oxidase and Nrf2/HO-1 pathway by vanillin in cisplatin-induced nephrotoxicity in rats

Younis

Elsherbiny

Shaheen

et al. 2020

Journal of Pharmacy and Pharmacology

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Objectives To investigate the protective effect of vanillin in cisplatin (CP)-induced nephrotoxicity in rats and elucidate the role of nrf-2 and its downstream antioxidant molecules. Methods Rats received vanillin (100 mg/kg orally) for 10 constitutive days and CP (7.5 mg/kg, once, ip) on day 6 of vanillin administration. Key findings Cisplatin suppressed body weight gain, increased serum urea and creatinine and renal malondialdehyde and nitric oxide while decreased renal total antioxidant capacity. Up-regulation of NADPH oxidase-4 (NOX-4) was marked in renal tissue of CP-treated rats along with down-regulation of the antioxidant genes (nuclear factor erythroid 2-related factor2 (NRF2) and haem oxygenase-1 (HO-1)). Increased tumour necrosis factor-a and decreased interleukin-10 with increased myeloperoxidase activity were apparent in renal tissue of CP-treated rats along with marked tubular injury, neutrophil infiltration and increased apoptosis (caspase-3) and some degree of interstitial fibrosis. Vanillin prophylactic administration prevented the deterioration of kidney function, oxidative and nitrosative stress. It also suppressed NOX-4 and up-regulated NRF2 and HO-1 expression in renal tissue. Inflammation, apoptosis and tubular injury were also inhibited by vanillin. Conclusions The antioxidant mechanism by which vanillin protected against CP-induced nephrotoxicity involved the inhibition of NOX-4 along with the stimulation of Nrf2/HO-1 signalling pathway. These in turn inhibited inflammation and apoptosis.

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“…The administration of 150 mg/kg/day F2 in mice significantly reduced tumor volume and tumor weight. Synergism between vanillin and doxorubicin showed similar results in Ehrlich solid tumors ( Elsherbiny et al, 2016 ). In vitro , F2 induced oxidative stress in cancer cells, resulting in intense lipoperoxidation.…”

Section: Discussionmentioning

confidence: 80%

Proanthocyanidin Polymer-Rich Fraction of Stryphnodendron adstringens Promotes in Vitro and in Vivo Cancer Cell Death via Oxidative Stress

et al. 2018

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Cervical cancer is the fourth most common cancer that affects women, mainly through human papilloma virus (HPV) infection with high-risk HPV16 and HPV18. The present study investigated the in vitro anticancer activity and mechanism of action of a proanthocyanidin polymer-rich fraction of Stryphnodendron adstringens (F2) in cervical cancer cell lines, including HeLa (HPV18-positive), SiHa (HPV16-positive), and C33A (HPV-negative) cells, and also evaluated in vivo anticancer activity. In vitro, cell viability was determined by the MTT assay. Cell migration was determined by the wound healing assay. The mechanism of action was investigated by performing ultrastructural analysis and evaluating reactive oxygen species (ROS) production, mitochondrial metabolism, lipoperoxidation, BCL-2 family expression, caspase expression, and DNA and cell membrane integrity. In vivo activity was evaluated using the murine Ehrlich solid tumor model. F2 time- and dose-dependently reduced cell viability and significantly inhibited the migration of cervical cancer cells. HeLa and SiHa cells treated with F2 (IC50) exhibited intense oxidative stress (i.e., increase in ROS and decrease in antioxidant species) and mitochondrial damage (i.e., mitochondrial membrane potential depolarization and a reduction of intracellular levels of adenosine triphosphate). Increases in the Bax/BCL-2 ratio and caspase 9 and caspase 3 expression, were observed, with DNA damage that was sufficient to trigger mitochondria-dependent apoptosis. Cell membrane disruption was observed in C33A cells (IC50 and IC90) and HeLa and SiHa cells (IC90), indicating progress to late apoptosis/necrosis. The inhibition of ROS production by N-acetylcysteine significantly suppressed oxidative stress in all three cell lines. In vivo, F2 significantly reduced tumor volume and weight of the Ehrlich solid tumor, and significantly increased lipoperoxidation, indicating that F2 also induces oxidative stress in the in vivo model. These findings indicate that the proanthocyanidin polymer-rich fraction of S. adstringens may be a potential chemotherapeutic candidate for cancer treatment.

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The synergistic effect between vanillin and doxorubicin in ehrlich ascites carcinoma solid tumor and MCF-7 human breast cancer cell line

Cited by 50 publications

References 30 publications

Gastroprotective Effect of Vanillin on Indomethacin-Induced Gastric Ulcer in Rats: Protective Pathways and Anti-Secretory Mechanism

Gastroprotective Effect of Vanillin on Indomethacin-Induced Gastric Ulcer in Rats: Protective Pathways and Anti-Secretory Mechanism

Modulation of NADPH oxidase and Nrf2/HO-1 pathway by vanillin in cisplatin-induced nephrotoxicity in rats

Proanthocyanidin Polymer-Rich Fraction of Stryphnodendron adstringens Promotes in Vitro and in Vivo Cancer Cell Death via Oxidative Stress

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