In conclusion, methanol leaves extract of C. nutans exhibited the highest cytotoxic activity against liver cancer cells (Hep-G2). There is a possibility that herb-drug interaction could occur with C. nutans through inhibitory effects on CYP3A4. Additionally, inhibition of C. nutans on CYP2E1 could show anti-carcinogenesis effects in human liver microsomes.

No abstract

Several studies have shown that the mammalian target of rapamycin (mTOR) inhibitor; everolimus (EV) improves patient survival in several types of cancer. However, the meaningful efficacy of EV as a single agent for the treatment of colorectal cancer (CRC) has failed to be proven in multiple clinical trials. Combination therapy is one of the options that could increase the efficacy and decrease the toxicity of the anticancer therapy. This study revealed that the β-cyclodextrin (β-CD):FGF7 complex has the potential to improve the antiproliferative effect of EV by preventing FGF receptor activation and by enhancing EV cellular uptake and intracellular retention. Molecular docking techniques were used to investigate the possible interaction between EV, β-CD, and FGF7. Molecular docking insights revealed that β-CD and EV are capable to form a stable inclusion complex with FGF at the molecular level. The aqueous solubility of the inclusion complex was increased (3.1 ± 0.23 μM) when compared to the aqueous solubility of pure EV (1.7 ± 0.16 μM). In addition, the in vitro cytotoxic activity of a FGF7:β-CD:EV complex on Caco-2 cell line was investigated using real-time xCELLigence technology. The FGF7:β-CD:EV complex has induced apoptosis of Caco-2 cells and shown higher cytotoxic activity than the parent drug EV. With the multitargets effect of β-CD:FGF7 and EV, the antiproliferative effect of EV was remarkably improved as the IC 50 value of EV was reduced from 9.65 ± 1.42 to 1.87 ± 0.33 μM when compared to FGF7:β-CD:EV complex activity. In conclusion, the findings advance the understanding of the biological combinational effects of the β-CD:FGF7 complex and EV as an effective treatment to combat CRC.

No abstract

Background: Recombinant human keratinocyte growth factor (rHuKGF) is a protein used to treat oral mucositis caused by radio and chemotherapy in patients with hematologic malignancy. The rHuKGF is available in the form of intravenous bolus injection. In this study, new formulation of rHuKGF-loaded chitosan nanoparticles was developed to improve patient compliance. Methods: Chitosan nanoparticles (CNPs) loaded with rHuKGF were prepared by ionic gelation method. The tripolyphosphate (TPP) cross-linked with chitosan molecules at pH >5.0 and form the nanoparticles. An infrared spectroscopic technique was conducted to confirm the formation of nanoparticles as a result of ionotropic interaction between TPP and chitosan. Zeta Sizer was used to determine the size, polydispersity index (PdI) and zeta potential of the prepared nanoparticles. The morphological characteristics of CNPs were measured by field emission scanning electron microscope. During the formation of CNPs, the rHuKGF was entrapped in the nanoparticles. The loading capacity of rHuKGF in CNPs was observed to be dependent on how much amount of rHuKGF/TPP solution was added to convert all the chitosan molecules to form nanoparticles. A double beam UV/Vis spectroscopic method was used to detect the formation of these rHuKGF loaded CNPs based on their optical properties. Results: The produced rHuKGF-loaded CNPs were colorless, cloudy, and positively charged monodisperse with a spherical shape. The prepared CNPs have particles size of 119 ± 74.62 nm, surface charge of +20.3 ± 6.46 mV and 0.217 polydispersity index. The shape of prepared CNPs was found to be spherical using field emission scanning electron microscope (FESEM). The interfacial polyelectrolyte complexation between TPP and chitosan was confirmed by comparing the FTIR spectra of TPP, chitosan, physical mixture of chitosan and TPP and CNPs. The loading capacity of the rHuKGF in CNPs was found to be 93.3 ± 2.02%. The formation of rHuKGF loaded CNPs was detected by double beam UV/Vis Spectroscopy at 232.2 nm. Conclusion: The results of the current work were utilized for designing a continuous monitoring and detection system for the formation of CNPs. The outcomes of this technique are useful to avoid the loss of rHuKGF during nanoparticle formation and improving the loading capacity of CNPs.