Coloaded Nanoparticles of Paclitaxel and Piperlongumine for Enhancing Synergistic Antitumor Activities and Reducing Toxicity

Liu, Qi; Zhao, Di; Zhu, Xiaojie; Chen, Huili; Yang, Yue; Xu, Jiaqiu; Zhang, Qing; Fan, Ali; Li, Ning; Guo, Chaorui; Kong, Ying; Lu, Yang; Chen, Xijing

doi:10.1016/j.xphs.2017.05.027

Cited by 19 publications

(12 citation statements)

References 36 publications

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“…Historically, much attention has been given to this molecule after its cytotoxicity and ability to induce the production of reactive oxygen species (ROS) selectively in cancer cells were published by Raj et al [ 12 ]. Later, the anticancer potential of piplartine and its analogs, alone or in combination, including combination with paclitaxel, cisplatin, gemcitabine and curcumin, have been extensively explored [ 10 , 16 , 19 – 21 ]. These studies reported the ability of piplartine to induce apoptosis and/or autophagy through modulation of the PI3K/Akt/mTOR, NF-κB, JAK1,2/STAT3 and/or JNK pathways in cancer cells [ 14 , 15 , 22 – 24 ].…”

Section: Introductionmentioning

confidence: 99%

Novel piplartine-containing ruthenium complexes: synthesis, cell growth inhibition, apoptosis induction and ROS production on HCT116 cells

Irs

et al. 2017

Oncotarget

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Piplartine (piperlongumine) is a plant-derived molecule that has been receiving intense interest due to its anticancer characteristics that target the oxidative stress. In the present paper, two novel piplartine-containing ruthenium complexes [Ru(piplartine)(dppf)(bipy)](PF6)2 (1) and [Ru(piplartine)(dppb)(bipy)](PF6)2 (2) were synthesized and investigated for their cellular and molecular responses on cancer cell lines. We found that both complexes are more potent than metal-free piplartine in a panel of cancer cell lines on monolayer cultures, as well in 3D model of cancer multicellular spheroids formed from human colon carcinoma HCT116 cells. Mechanistic studies uncovered that the complexes reduced the cell growth and caused phosphatidylserine externalization, internucleosomal DNA fragmentation, caspase-3 activation and loss of the mitochondrial transmembrane potential on HCT116 cells. Moreover, the pre-treatment with Z-VAD(OMe)-FMK, a pan-caspase inhibitor, reduced the complexes-induced apoptosis, indicating cell death by apoptosis through caspase-dependent and mitochondrial intrinsic pathways. Treatment with the complexes also caused a marked increase in the production of reactive oxygen species (ROS), including hydrogen peroxide, superoxide anion and nitric oxide, and decreased reduced glutathione levels. Application of N-acetyl-cysteine, an antioxidant, reduced the ROS levels and apoptosis induced by the complexes, indicating activation of ROS-mediated apoptosis pathway. RNA transcripts of several genes, including gene related to the cell cycle, apoptosis and oxidative stress, were regulated under treatment. However, the complexes failed to induce DNA intercalation. In conclusion, the complexes are more potent than piplartine against different cancer cell lines and are able to induce caspase-dependent and mitochondrial intrinsic apoptosis on HCT116 cells by ROS-mediated pathway.

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Section: Introductionmentioning

confidence: 99%

Novel piplartine-containing ruthenium complexes: synthesis, cell growth inhibition, apoptosis induction and ROS production on HCT116 cells

Irs

et al. 2017

Oncotarget

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“…Recent studies have demonstrated that overexpression of HK2 was involved in chemotherapy resistance in human cancers. Given the effect of PL on HK-2, which may further help us to understand the mechanism why PL has the synergistic effect to promote the anti-tumor effect of chemotherapy drugs, such as cisplatin and 5-Fu [59,60]. Briefly, the present study identified PL as a novel therapeutic agent to regulate glycolysis in NSCLC cells and could provide a new option for clinical combination treatment of NSCLC.…”

Section: Discussionmentioning

confidence: 75%

Repression of Hexokinases II-Mediated Glycolysis Contributes to Piperlongumine-Induced Tumor Suppression in Non-Small Cell Lung Cancer Cells

Zhou

Yu³

et al. 2019

Int. J. Biol. Sci.

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Deregulation of glycolysis is a common phenomenon in human non-small cell lung cancer (NSCLC). In the present study, we reported the natural compound, piperlongumine, has a profound anti-tumor effect on NSCLC via regulation of glycolysis. Piperlongumine suppressed the proliferation, colony formation and HK2-mediated glycolysis in NSCLC cells. We demonstrated that exposure to piperlongumine disrupted the interaction between HK2 and VDAC1, induced the activation of the intrinsic apoptosis signaling pathway. Moreover, our results revealed that piperlongumine down-regulated the Akt signaling, exogenous overexpression of constitutively activated Akt1 in HCC827 and H1975 cells significantly rescued piperlongumine-induced glycolysis suppression and apoptosis. The xenograft mouse model data demonstrated the pivotal role of suppression of Akt activation and HK2-mediated glycolysis in mediating the in vivo antitumor effects of piperlongumine. The expression of HK2 was higher in malignant NSCLC tissues than that of the paired adjacent tissues, and was positively correlated with poor survival time. Our results suggest that HK2 could be used as a potential predictor of survival and targeting HK2 appears to be a new approach for clinical NSCLC prevention or treatment.

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“…The three natural molecules were found to reduce the toxicity issues in animal studies. The researchers have synthesized the individual NPs of Q, P and C [34][35][36]. The combinatorial approach of action of more than one molecules on cancer was quite good in few studies [37].…”

Section: Distribution Of Quercetin Piperlongumine and Curcumin In DImentioning

confidence: 99%

Combinatorial Approach of poly-D, L-lactide Encapsulated Quercetin, Piperlongumine and Curcumin Inhibits Tumour Growth in Balb/c Mice, the Colon Cancer Model

Chaudhary

2021

Preprint

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Colon cancer has become an extreme danger to human lives due to high frequency and mortality around the world. The natural formulations based on the nanoparticles have been found promising in terms of cost, procedure and side effects. In this study, for the first time, three natural molecules- quercetin, piperlongumine and curcumin were encapsulated in biodegradable poly-D,L-lactide nanoparticles to check their anticancer potential against the colon cancer (DMH-DSS). The pure molecules, blank and loaded nanoparticles were given to the colon cancer model (BALB/c mice) and evaluated the anticancer potential of the nano-formulations. Ficus benghalensis (Banyan) coated nanoparticles maintained the detectable concentration of quercetin, piperlongumine and curcumin in colon even in liver, kidney and serum after 8 h of administration. In case of sugar coated NPs, quercetin, piperlongumine and curcumin were detected in colon, kidney and liver. Further, it was found that the coating of nanoparticles surface with leaf extract and dextrose sugar enhanced the potential of the formulation. This newly synthesized formulation can have the potential to be explored further as anticancer drug against the colon cancer.

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Coloaded Nanoparticles of Paclitaxel and Piperlongumine for Enhancing Synergistic Antitumor Activities and Reducing Toxicity

Cited by 19 publications

References 36 publications

Novel piplartine-containing ruthenium complexes: synthesis, cell growth inhibition, apoptosis induction and ROS production on HCT116 cells

Novel piplartine-containing ruthenium complexes: synthesis, cell growth inhibition, apoptosis induction and ROS production on HCT116 cells

Repression of Hexokinases II-Mediated Glycolysis Contributes to Piperlongumine-Induced Tumor Suppression in Non-Small Cell Lung Cancer Cells

Combinatorial Approach of poly-D, L-lactide Encapsulated Quercetin, Piperlongumine and Curcumin Inhibits Tumour Growth in Balb/c Mice, the Colon Cancer Model

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