Antitumor activity of gambogic acid on NCI-H1993 xenografts via MET signaling pathway downregulation

Li, Donglei; Yang, Haisheng; Li, Runpu; Wang, Yanli; Li, Dongjie; Ma, Shaolin; Zhang, Xuyu

doi:10.3892/ol.2015.3719

Cited by 12 publications

(4 citation statements)

References 18 publications

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“… 14 Also, GA exhibits anticancer effects on NCI-H1993 xenografts by regulation of the MET signal pathway. 15 GA is a prospective antitumor drug with less toxic effects on the normal tissues, 16 which has been authorized for the treatment of variety of cancer in clinical trials by the Chinese Food and Drug Administration. 17 A Phase IIa clinical study suggests that GA administered at 45 mg/m 2 is safe.…”

Section: Introductionmentioning

confidence: 99%

Combination of gambogic acid with cisplatin enhances the antitumor effects on cisplatin-resistant lung cancer cells by downregulating MRP2 and LRP expression

Zhang¹,

Zhou²,

Yu³

et al. 2016

OTT

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Cisplatin resistance is a main clinical problem of lung cancer therapy. Gambogic acid (GA) could prohibit the proliferation of a variety of human cancer cells. However, the effects of GA on cisplatin-resistant lung cancer are still unclear. The objective of the present study was to find out the antitumor effects of GA on cisplatin-resistant human lung cancer A549/DDP cells and further explore its underlying mechanisms. Cell Counting Kit-8 assay was used to observe the impacts of GA and/or cisplatin on the proliferation of lung cancer cells; flow cytometry was used to detect the effects of GA on cell cycle and apoptosis; Western blot was used to examine the effects of GA on the expression of lung resistance protein (LRP) and multidrug resistance-associated protein 2 (MRP2) protein in A549/DDP cells. Our results showed that GA dose- and time-dependently prohibited the proliferation and induced significant cell apoptosis in A549 and A549/DDP cells. GA also induced G0/G1 arrest in both A549/DDP and A549 cells. Moreover, GA upregulated protein expression level of cleaved caspase-3 and Bax and downregulated protein expression level of pro-caspase-9 and Bcl-2 in time- and dose-dependent way in A549/DDP cells. GA combined with cisplatin enhanced the cells apoptotic rate and reduced the cisplatin resistance index in A549/DDP cells. In addition, GA reduced the MRP2 and LRP protein expression level in A549/DDP cells. GA inhibits the proliferation, induces cell cycle arrest and apoptosis in A549/DDP cells. Combination of GA with cisplatin enhances the antitumor effects on cisplatin-resistant lung cancer cells by downregulating MRP2 and LRP expression.

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Section: Introductionmentioning

confidence: 99%

Combination of gambogic acid with cisplatin enhances the antitumor effects on cisplatin-resistant lung cancer cells by downregulating MRP2 and LRP expression

Zhang¹,

Zhou²,

Yu³

et al. 2016

OTT

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“…GA has also been implicated in several mechanisms of cisplatin resistance (18). Furthermore, it has exhibited detectable effects on patients with lung cancer, colorectal cancer and renal cell carcinoma (19)(20)(21). Thus, GA has been approved for evaluation in a phase II clinical trial for NSCLC in China (approval no.…”

Section: Introductionmentioning

confidence: 99%

Role of gambogic acid and NaI131 in A549/DDP cells

et al. 2016

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Abstract. Resistance to platinum in tumor tissue is a considerable barrier against effective lung cancer treatment. Radionuclide therapy is the primary adjuvant treatment, however, the toxic side effects limit its dosage in the clinical setting. Therefore, the present study aimed to determine whether an NaI 131 radiosensitizer could help reduce the toxic side effects of radionuclide therapy. In vitro experiments were conducted to determine whether NaI 131 can inhibit platinum resistance in A549/DDP cells, which are cisplatin-resistant non-small cell lung cancer cells, and whether gambogic acid (GA) is an effective NaI 131 radiosensitizer. Cell proliferation following drug intervention was analyzed using MTT and isobolographic analysis. Apoptosis was assessed by flow cytometry. In addition, the mechanisms of drug intervention were analyzed by measuring the expression of P-glycoprotein (P-gP), B cell lymphoma 2 (Bcl-2), Bcl2-associated X protein (Bax) and P53 using western blot analysis and immunocytochemistry. According to isobolographic analysis, a low concentration of NaI 131 combined with GA had a synergistic effect on the inhibition of A549/DDP cell proliferation, which was consistent with an increased rate of apoptosis. Furthermore, the overexpression of Bax, and the downregulation of P-gP, P53 and Bcl-2 observed demonstrated the potential mechanism(s) of NaI 131 and GA intervention. NaI 131 may induce apoptosis in A549/DDP cells by regulating apoptosis-related proteins. A low concentration combination of NaI 131 and GA was able to significantly inhibit A549/DDP cell proliferation and induce cell apoptosis. Thus, the two drugs appear to have a synergistic effect on apoptosis of A549/DDP cells.

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“…F 2. GA has been proven to exhibit anti-proliferative effect, induce apoptosis, reverse multidrug resistance and possess anti-angiogenic properties on certain tumors, such as breast, prostate, lung and pancreatic cancer cells 3–8. GA has a unique caged xanthone structure, and has multiple targets, including the Bcl-2 family proteins, redox regulatory proteins, NF-ᴋB, and integrin pathways 9.…”

Section: Introductionmentioning

confidence: 99%

<p>Dimeric c(RGD) peptide conjugated nanostructured lipid carriers for efficient delivery of Gambogic acid to breast cancer</p>

Kebebe¹,

Wu²,

Zhang³

et al. 2019

IJN

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Background and purpose: Gambogic acid (GA) is a natural compound that exhibited a promising multi-target antitumor activity against several types of cancer. However, the clinical application of this drug is limited due to its poor solubility and low tumor cell-specific delivery. In this study, the monomeric and dimeric Cyclo (Arg-Gly-Asp) c(RGD) tumor targeting peptides (c(RGDfK) and E-[c(RGDfK) 2 ]) were used to modify GA loaded nanostructured lipid carriers (NLC) to reduce the limitations associated with GA and improve its antitumor activity. Methods: GA-NLC was prepared by emulsification and solvent evaporation methods and the surface of the NLC was conjugated with the c(RGD) peptides via an amide bond. The formulations were characterized for particle size, morphology and zeta potential, encapsulation efficiency and drug loading. The in-vitro cytotoxicity and cell uptake studies were conducted using 4T1 cell. Furthermore, the in-vivo antitumor activity and bio-distribution study were performed on female BALB/c nude mice. Results: The c(RGD) peptides modified GA-NLC was successfully prepared with the particles size about 20 nm. The HPLC analysis, FT-IR and 1 H-NMR spectra confirmed the successful conjugation of the peptides with the NLC. The in-vitro cytotoxicity study on 4T1 cells revealed that c(RGD) peptides modified GA-NLCs showed significantly higher cytotoxicity at 0.25 and 0.5 µg/mL as compared to unmodified GA-NLC. Furthermore, the cell uptake study demonstrated that better accumulation of E-[c(RGDfK) 2 ] peptides modified NLC in 4T1 cell after 12 h incubation. Moreover, the in-vivo study showed that c(RGD)s functionalized GA-NLC exhibited better accumulation in tumor tissue and tumor growth inhibition. In contrast to the monomeric c(RGD) peptide, the dimeric c(RGD) peptide (E-[c(RGDfK) 2 ]) conjugated GA-NLC showed the improved antitumor activity and tumor targeting ability of GA-NLC. Conclusion: These data provide further support for the potential clinical applications of E-[c(RGDfK) 2 ]-GA-NLC in breast cancer therapy.

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Antitumor activity of gambogic acid on NCI-H1993 xenografts via MET signaling pathway downregulation

Cited by 12 publications

References 18 publications

Combination of gambogic acid with cisplatin enhances the antitumor effects on cisplatin-resistant lung cancer cells by downregulating MRP2 and LRP expression

Combination of gambogic acid with cisplatin enhances the antitumor effects on cisplatin-resistant lung cancer cells by downregulating MRP2 and LRP expression

Role of gambogic acid and NaI131 in A549/DDP cells

<p>Dimeric c(RGD) peptide conjugated nanostructured lipid carriers for efficient delivery of Gambogic acid to breast cancer</p>

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