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Punfa, Wanisa,Suzuki, Shugo,Pitchakarn, Pornsiri,Yodkeeree, Supachai,Naiki, Taku,Takahashi, Satoru,Limtrakul, Pornngarm Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.21
Background: The encapsulation of curcumin (Cur) in polylactic-co-glycolic acid (PLGA) nanoparticles (Cur-NPs) was designed to improve its solubility and stability. Conjugation of the Cur-NPs with anti-P-glycoprotein (P-gp) antibody (Cur-NPs-APgp) may increase their targeting to P-gp, which is highly expressed in multidrugresistance (MDR) cancer cells. This study determined whether Cur-NPs-APgp could overcome MDR in a human cervical cancer model (KB-V1 cells) in vitro and in vivo. Materials and Methods: First, we determined the MDR-reversing property of Cur in P-gp-overexpressing KB-V1 cells in vitro and in vivo. Cur-NPs and Cur-NPs-APgp, in the range 150-180 nm, were constructed and subjected to an in vivo pharmacokinetic study compared with Cur. The in vitro and in vivo MDR-reversing properties of Cur-NPs and Cur-NPs-APgp were then investigated. Moreover, the stability of the NPs was determined in various solutions. Results: The combined treatment of paclitaxel (PTX) with Cur dramatically decreased cell viability and tumor growth compared to PTX treatment alone. After intravenous injection, Cur-NPs-APgp and Cur-NPs could be detected in the serum up to 60 and 120 min later, respectively, whereas Cur was not detected after 30 min. Pretreatment with Cur-NPs-APgp, but not with NPs or Cur-NPs, could enhance PTX sensitivity both in vitro and in vivo. The constructed NPs remained a consistent size, proving their stability in various solutions. Conclusions: Our functional Cur-NPs-APgp may be a suitable candidate for application in a drug delivery system for overcoming drug resistance. The further development of Cur-NPs-APgp may be beneficial to cancer patients by leading to its use as either as a MDR modulator or as an anticancer drug.
Anti-P-glycoprotein Conjugated Nanoparticles for Targeting Drug Delivery in Cancer Treatment
Pantiwa Iangcharoen,Wanisa Punfa,Supachai Yodkeeree,Watchara Kasinrerk,Chadarat Ampasavate,Songyot Anuchapreeda,Pornngarm Limtrakul 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.10
Targeting therapeutics to specific sites can enhance the efficacy of drugs, reduce required doses as well as unwanted side effects. In this work, using the advantages of the specific affinity of an immobilized antibody to membrane P-gp in two different nanoparticle formulations were thus developed for targeted drug delivery to multi-drug resistant cervical carcinoma (KB-V1) cells. Further, this was compared to the human drug sensitive cervical carcinoma cell line (KB-3-1) cells. The two nanoparticle preparations were: NP1, anti-P-gp conjugated with poly (DL-lactic-coglycolic acid) (PLGA) nanoparticle and polyethylene glycol (PEG); NP2, anti-P-gp conjugated to a modified poloxamer on PLGA nanoparticles. The cellular uptake capacity of nanoparticles was confirmed by fluorescent microscopy. Comparing with each counterpart core particles, there was a higher fluorescence intensity of the targeted nanoparticles in KBV1 cells compared to KB-3-1 cells suggesting that the targeted nanoparticles were internalized into KB-V1 cells to a greater extent than KB-3-1 cell. The results had confirmed the specificity and the potential of the developed targeted delivery system for overcoming multi-drug resistance induced by overexpression of P-gp on the cell membrane.
Pornngarm Limtrakul,Supachai Yodkeeree,Pornsiri Pitchakarn,Wanisa Punfa 대한지역사회영양학회 2016 Nutrition Research and Practice Vol.10 No.3
BACKGROUND/OBJECTIVES: Several pharmacological properties of red rice extract have been reported including anti-oxidant, anti-tumor, and reduced cancer cell invasion. This study was conducted to evaluate the anti-inflammatory effects of red rice extract on the production of inflammatory mediators in lipopolysaccharide (LPS)-induced Raw 264.7 macrophages. MATERIALS/METHODS: Pro-inflammatory cytokines including tumor necrosis factor-α and interleukin-6 were determined by ELISA and cyclooxygenase-2 and inducible nitric oxide synthase expression was evaluated using western blot analysis. In addition, the signaling pathway controlling the inflammatory cascade such as nuclear factor kappa B (NF-κB), activator proteins-1 (AP-1), and mitogen-activated protein kinase (MAPK) was determined. RESULTS: Our results showed that red rice polar extract fraction (RR-P), but not non-polar extract fraction, inhibited interleukin-6, tumor necrosis factor-α, and nitric oxide production in LPS-induced Raw 264.7 cells. RR-P also reduced the expression of inflammatory enzymes, inducible nitric oxide synthase, and cyclooxygenase-2. In addition, activation of AP-1 and NF-κB transcription factor in the nucleus was abrogated by RR-P. RR-P inhibited the phosphorylation of extracellular signaling-regulated kinase 1/2, c-Jun NH2-terminal kinase, and p38 MAPK signaling responsible for the expression of inflammatory mediators in LPS-stimulated Raw 264.7 cells. Based on chemical analysis, high amounts of proanthocyanidin and catechins were detected in the RR-P fraction. However, only proanthocyanidin reduced NF-κB and AP-1 activation in LPS-activated Raw 264.7 cells. CONCLUSION: These observations suggest that the anti-inflammatory properties of RR-P may stem from the inhibition of pro-inflammatory mediators via suppression of the AP-1, NF-κB, and MAPKs pathways.
Limtrakul, Pornngarm,Yodkeeree, Supachai,Pitchakarn, Pornsiri,Punfa, Wanisa Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.10
Anthocyanin, a phenolic compound, has been reported to have an anti-inflammatory effect against lipopolysaccharide (LPS) induced changes in immune cells. However, little is known about the molecular mechanisms underlying its anti-inflammatory effects. Few research studies have concerned the anti-inflammation properties of colored rice extract as a functional material. Therefore, the purpose of this study was to examine anti-inflammatory effects of the polar fraction of black rice whole grain extracts (BR-WG-P) that features a high anthocyanin content. Our results showed that BR-WG-P significantly inhibited LPS-induced pro-inflammatory mediators, including production of NO and expression of iNOS and COX-2. In addition, secretion of pro-inflammatory cytokines including TNF-${\alpha}$ and IL-6 was also significantly inhibited. Moreover, BR-WG-P and anthocyanin inhibited NF-kB and AP-1 translocation into the nucleus. BR-WG-P also decreased the phosphorylation of ERK, p38 and JNK in a dose dependent manner. These results suggested that BR-WG-P might suppress LPS-induced inflammation via the inhibition of the MAPK signaling pathway leading to decrease of NF-kB and AP-1 translocation. All of these results indicate that BR-WG-P exhibits therapeutic potential associated with the anthocyanin content in the extract for treating inflammatory diseases associated with cancer.