Immunotherapeutic vitamin E nanoemulsion synergies the antiproliferative activity of paclitaxel in breast cancer cells via modulating Th1 and Th2 immune response

Pawar, Vivek K.; Panchal, Samir B.; Singh, Yuvraj; Meher, Jaya Gopal; Sharma, Komal; Singh, Pankaj Kumar; Bora, Himangshu K.; Singh, Atul Kumar; Datta, Dipak; Chourasia, Manish K.

doi:10.1016/j.jconrel.2014.10.010

Cited by 75 publications

(47 citation statements)

References 33 publications

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“…To evaluate whether the robust cytotoxic effect of CFEA observed in-vitro would also result in tumor volume reduction in-vivo , we examined the efficacy of CFEA in a syngenic breast tumor mouse model, previously established in our lab 32 . We have selected 50 mg/kg of body weight oral dose of CFEA for our in-vivo studies by performing initial pharmacokinetic studies of its active components.…”

Section: Resultsmentioning

confidence: 99%

“…We have used 4T1 syngenic mouse model to test the in-vivo efficacy of CFEA as it better mimics human breast cancer in an immune-competent condition. As described previously 32 , mouse breast cancer 4T1 cells (10 6 ) were injected subcutaneously into mammary fat pad on right flank of each 4–6 week old female Balb/c mouse and were allowed to grow palpable tumors. Treatments were given once every day by oral gavage for two weeks.…”

Section: Methodsmentioning

confidence: 99%

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Anti-breast tumor activity of Eclipta extract in-vitro and in-vivo: novel evidence of endoplasmic reticulum specific localization of Hsp60 during apoptosis

Arya

Singh

Yadav³

et al. 2015

Sci Rep

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Major challenges for current therapeutic strategies against breast cancer are associated with drug-induced toxicities. Considering the immense potential of bioactive phytochemicals to deliver non-toxic, efficient anti-cancer therapeutics, we performed bio-guided fractionation of Eclipta alba extract and discovered that particularly the chloroform fraction of Eclipta alba (CFEA) is selectively inducing cytotoxicity to breast cancer cells over non-tumorigenic breast epithelial cells. Our unbiased mechanistic hunt revealed that CFEA specifically activates the intrinsic apoptotic pathway by disrupting the mitochondrial membrane potential, upregulating Hsp60 and downregulating the expression of anti-apoptotic protein XIAP. By utilizing Hsp60 specific siRNA, we identified a novel pro-apoptotic role of Hsp60 and uncovered that following CFEA treatment, upregulated Hsp60 is localized in the endoplasmic reticulum (ER). To our knowledge, this is the first evidence of ER specific localization of Hsp60 during cancer cell apoptosis. Further, our LC-MS approach identified that luteolin is mainly attributed for its anti-cancer activities. Moreover, oral administration of CFEA not only offers potential anti-breast cancer effects in-vivo but also mitigates tumor induced hepato-renal toxicity. Together, our studies offer novel mechanistic insight into the CFEA mediated inhibition of breast cancer and may potentially open up new avenues for further translational research.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Anti-breast tumor activity of Eclipta extract in-vitro and in-vivo: novel evidence of endoplasmic reticulum specific localization of Hsp60 during apoptosis

Arya

Singh

Yadav³

et al. 2015

Sci Rep

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“…Moreover, the PTX nano-emulsion has benefits with increased in-vivo anticancer activity, and associated with lower in vivo toxicity and altered pharmacokinetic profile AUC and MRT were extended. 48,49 In sum, this shows the importance vitamin E in boosting the pharmacological and immunological responses when combined with PTX in breast cancer.…”

mentioning

confidence: 89%

Immunotherapy Options for Cancer

Ananthula

Chowdhury

2017

MOJBB

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Cancer is a heterogeneous disease originated from various parts of the body and characterized mainly based upon the type of cells or tissue it originated from. In early years of cancer research, it was considered that a "magic drug" can be developed to treat all types of cancers. However, this notion was proven wrong through years of research as various forms of cancer emerged that are variant between individuals and are hard to treat or even control. Clonal survival of cancer cells is the major hurdle limiting the therapeutic response in patient. Cancer progression leads to immunocompromised state in patients resulting in fast disease progression and higher susceptibility to infections. Tumor infiltrated T cells, tumor associated macrophages, mesenchymal stem cells and other immune cells support the clonal development in cancer tissue leading to its rapid growth and metastasis. In recent years, immunotherapy of cancer is the major interest among researchers. Chimeric antigen receptor (CAR) T cell therapy, immune check point targeting, or boosting the immune system in patient are the approaches being implemented in cancer immunotherapy. Present review discusses the various immunotherapy options for cancer and explains importance of considering the treatment/prevention with natural compounds.

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“…Taking note, our group has also attempted a slightly altered Vitamin E nanoemulsion of paclitaxel to accentuate inherent anti-proliferative and immune therapeutic activity of Vitamin E. We found that drug loaded nanoemulsion substantially enhanced anticancer activity of paclitaxel by opening up alternative pathways of mitochondrial killing, pharmacokinetic improvement, and immune modulation. Overall safety (measured by serum markers and organ histology) was also improved (Pawar et al, 2014). O/W parenteral lipid nanoemulsion of diclofenac has been investigated for treatment of arthritic conditions.…”

Section: Kinetics Of Drug Releasementioning

confidence: 99%

Nanoemulsion: A brief review on development and application in Parenteral Drug Delivery

Nikam¹,

Patil²,

Patil³

et al. 2018

Adv Pharm J

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An advanced mode of drug delivery system has been developed to overcome the major drawbacks associated with conventional drug delivery systems. This review gives a detailed idea about a nanoemulsion system. Nanoemulsions are nano-sized emulsions, which are manufactured for improving the delivery of active pharmaceutical ingredients. These are the thermodynamically stable isotropic system in which two immiscible liquids are mixed to form a single phase by means of an emulsifying agent, i.e., surfactant and co-surfactant. The droplet size of nanoemulsion falls typically in the range 20-200 nm. Nanoemulsions are biphasic dispersion of two immiscible liquids: either water in oil (W/O) or oil in water (O/W) droplets stabilized by an amphiphilic surfactant. These come across as ultrafine dispersions whose differential drug loading; viscoelastic as well as visual properties can cater to a wide range of functionalities including drug delivery. However there is still relatively narrow in sight regarding development, manufacturing, fabrication and manipulation of nanoemulsions which primarily stems from the fact that conventional aspects of emulsion formation and stabilization only partially apply to nanoemulsions. This general deficiency sets up the premise for current review. We attempt to explore varying intricacies, excipients, manufacturing techniques and their underlying principles, production conditions, structural dynamics, prevalent destabilization mechanisms, and drug delivery applications of nanoemulsions to spike interest of those contemplating a foray in this field.

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Immunotherapeutic vitamin E nanoemulsion synergies the antiproliferative activity of paclitaxel in breast cancer cells via modulating Th1 and Th2 immune response

Cited by 75 publications

References 33 publications

Anti-breast tumor activity of Eclipta extract in-vitro and in-vivo: novel evidence of endoplasmic reticulum specific localization of Hsp60 during apoptosis

Anti-breast tumor activity of Eclipta extract in-vitro and in-vivo: novel evidence of endoplasmic reticulum specific localization of Hsp60 during apoptosis

Immunotherapy Options for Cancer

Nanoemulsion: A brief review on development and application in Parenteral Drug Delivery

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