scholarly journals In Vitro Cell Toxicity and Intracellular Uptake of Doxorubicin Exposed as a Solution or Liposomes: Implications for Treatment of Hepatocellular Carcinoma

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1717
Author(s):  
Fredrik Kullenberg ◽  
Oliver Degerstedt ◽  
Carlemi Calitz ◽  
Nataša Pavlović ◽  
David Balgoma ◽  
...  

Cytostatic effects of doxorubicin in clinically applied doses are often inadequate and limited by systemic toxicity. The main objective of this in vitro study was to determine the anti-tumoral effect (IC50) and intracellular accumulation of free and liposomal doxorubicin (DOX) in four human cancer cell lines (HepG2, Huh7, SNU449 and MCF7). The results of this study showed a correlation between longer DOX exposure time and lower IC50 values, which can be attributed to an increased cellular uptake and intracellular exposure of DOX, ultimately leading to cell death. We found that the total intracellular concentrations of DOX were a median value of 230 times higher than the exposure concentrations after exposure to free DOX. The intracellular uptake of DOX from solution was at least 10 times higher than from liposomal formulation. A physiologically based pharmacokinetic model was developed to translate these novel quantitative findings to a clinical context and to simulate clinically relevant drug concentration–time curves. This showed that a liver tumor resembling the liver cancer cell line SNU449, the most resistant cell line in this study, would not reach therapeutic exposure at a standard clinical parenteral dose of doxorubicin (50 mg/m2), which is serious limitation for this drug. This study emphasizes the importance of in-vitro to in-vivo translations in the assessment of clinical consequence of experimental findings.

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Quang Trung Nguyen ◽  
Phuong Nam Pham Thi ◽  
Nguyen Van Tuyen

Six Fe(III) complexes bearing unsymmetrical salen-type ligands derived from 2-hydroxynaphthaldehyde and substituted salicylaldehydes were synthesized by coordinating the unsymmetrical salen-type ligands with FeCl3.6H2O. The synthetic complexes were characterized by electrospray ionization mass spectra (ESI-MS), effective magnetic moments (μeff), and infrared (IR) and ultraviolet-visible (UV-Vis) spectra. The spectroscopic data are in good agreement with the suggested molecular formulae of the complexes. Their cyclic voltammetric studies in acetonitrile solutions showed that the Fe(III)/Fe(II) reduction processes are electrochemically irreversible. The in vitro cytotoxicity of the obtained complexes was screened on human cancer cell lines KB (a subline of Hela tumor cell line) and HepG2 (a human liver cancer cell line) and a normal human cell line HEK-293 (Human Embryonic Kidney cell line). The results showed that the synthetic Fe(III) complexes are highly cytotoxic and quite selective. The synthetic complexes bearing unsymmetrical salen-type ligands with different substituted groups in the salicyl ring indicate different cytotoxicity.


1998 ◽  
Vol 41 (3) ◽  
pp. 669-674 ◽  
Author(s):  
Takeshi Ebara ◽  
Norio Mitsuhashi ◽  
Yoshihiro Saito ◽  
Tetsuo Akimoto ◽  
Hideo Niibe

2018 ◽  
Vol 18 (17) ◽  
pp. 1483-1493
Author(s):  
Ricardo Imbroisi Filho ◽  
Daniel T.G. Gonzaga ◽  
Thainá M. Demaria ◽  
João G.B. Leandro ◽  
Dora C.S. Costa ◽  
...  

Background: Cancer is a major cause of death worldwide, despite many different drugs available to treat the disease. This high mortality rate is largely due to the complexity of the disease, which results from several genetic and epigenetic changes. Therefore, researchers are constantly searching for novel drugs that can target different and multiple aspects of cancer. Experimental: After a screening, we selected one novel molecule, out of ninety-four triazole derivatives, that strongly affects the viability and proliferation of the human breast cancer cell line MCF-7, with minimal effects on non-cancer cells. The drug, named DAN94, induced a dose-dependent decrease in MCF-7 cells viability, with an IC50 of 3.2 ± 0.2 µM. Additionally, DAN94 interfered with mitochondria metabolism promoting reactive oxygen species production, triggering apoptosis and arresting the cancer cells on G1/G0 phase of cell cycle, inhibiting cell proliferation. These effects are not observed when the drug was tested in the non-cancer cell line MCF10A. Using a mouse model with xenograft tumor implants, the drug preventing tumor growth presented no toxicity for the animal and without altering biochemical markers of hepatic function. Results and Conclusion: The novel drug DAN94 is selective for cancer cells, targeting the mitochondrial metabolism, which culminates in the cancer cell death. In the end, DAN94 has been shown to be a promising drug for controlling breast cancer with minimal undesirable effects.


2014 ◽  
Vol 8 (Suppl 4) ◽  
pp. P22
Author(s):  
Klesia Madeira ◽  
Murilo Cerri ◽  
Renata Daltoé ◽  
Alice Herlinger ◽  
João Filho ◽  
...  

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 805-808
Author(s):  
Ravikumar Raju ◽  
Teja ◽  
Sravanathi P ◽  
Muthu Babu K

Breast cancer is the subsequent foremost reason of cancer death in a woman and ranks as the primary foremost reason of death in India. In its conduct, several measures and recommendation are considered. Homoeopathic medicines are one of the part of a corresponding, and another medicine is utilized for the treatment of cancer. The main purpose of the investigation is to evaluate the anticancer action of homoeopathic arrangements of Asterias rubens  on the basis of the similia principle. We directed an in vitro study using MTT assay to control the result of ultra diluted homoeopathic preparation in contradiction of two human breast glandular cancer cell lines(MCF-7 and MDA-MD- 231), frequently used for the breast cancer treatment, by testing the feasibility of breast cancer (MCF-7 and MDA-MD-231) cell line, with various attenuations of Asterias rubens  at 24 hrs. Multiple comparisons between tested reagents at different concentrations confirmed the significance of the said results. At a dilution of 1:25 6CH and 30CH potency shown superior activity on MCF-7 and no such significant changes on MDA-MD-231 at any dilutions As it fails to offer estrogen receptor(ER) Also progesterone receptor (PR) expression, and also HER2 (human epidermal development variable receptor2) so continuously a triple-negative breast cancer it will be a hostility manifestation for breast cancer with restricted medicine choices. However, further potency needs to be tested. These preliminary significant results warrant further in vitro and in vivo studies to estimate the possible of Asterias rubens  a medicine to treat breast cancer.


Plants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1031 ◽  
Author(s):  
Sameh S. Elhady ◽  
Enas E. Eltamany ◽  
Amera E. Shaaban ◽  
Alaa A. Bagalagel ◽  
Yosra A. Muhammad ◽  
...  

Phytochemical study of Chiliadenus montanus aerial parts afforded six compounds; Intermedeol (1), 5α-hydroperoxy-β-eudesmol (2), 5,7-dihydroxy-3,3’,4’-trimethoxyflavone (3), 5,7,4’-trihydroxy-3,6,3’-trimethoxyflavone (jaceidin) (4), eudesm-11,13-ene-1β,4β,7α-triol (5) and 1β,4β,7β,11-tetrahydroxyeudesmane (6). These compounds were identified based on their NMR spectral data. The isolated compounds were tested for their cytotoxicity against liver cancer cell line (HepG2) and breast cancer cell line (MCF-7). Jaceidin flavonoid (4) exhibited the highest cytotoxic effect in vitro. Therefore, both of jaceidin and C. montanus extract were evaluated for their in vivo anti-tumor activity against Ehrlich’s ascites carcinoma (EAC). Compared to control group, jaceidin and C. montanus extract decreased the tumor weight, improved the histological picture of tumor cells, lowered the levels of VEGF and ameliorate the oxidative stress. Molecular docking and in silico studies suggested that jaceidin was a selective inhibitor of VEGF-mediated angiogenesis with excellent membrane permeability and oral bioavailability.


2011 ◽  
Vol 66 (3-4) ◽  
pp. 143-148 ◽  
Author(s):  
Hossam M. Abdallah ◽  
Shahira M. Ezzat

The aerial parts of Pituranthos tortuosus (Desf.) Benth and Hook (Apiaceae), growing wild in Egypt, yielded 0.8%, 0.6%, and 1.5% (v/w) of essential oil when prepared by hydrodistillation (HD), simultaneous hydrodistillation-solvent (n-pentane) extraction (Lickens- Nickerson, DE), and conventional volatile solvent extraction (preparation of the “absolute”, SE), respectively. GC-MS analysis showed that the major components in the HD sample were β-myrcene (18.81%), sabinene (18.49%), trans-iso-elemicin (12.90%), and terpinen- 4-ol (8.09%); those predominent in the DE sample were terpinen-4-ol (29.65%), sabinene (7.38%), γ-terpinene (7.27%), and β-myrcene (5.53%); while the prominent ones in the SE sample were terpinen-4-ol (15.40%), dill apiol (7.90%), and allo-ocimene (4E,6Z) (6.00%). The oil prepared in each case was tested for its cytotoxic activity on three human cancer cell lines, i.e. liver cancer cell line (HEPG2), colon cancer cell line (HCT116), and breast cancer cell line (MCF7). The DE sample showed the most potent activity against the three human cancer cell lines (with IC50 values of 1.67, 1.34, and 3.38 μg/ml against the liver, colon, and breast cancer cell lines, respectively). Terpinen-4-ol, sabinene, γ-terpinene, and β-myrcene were isolated from the DE sample and subjected to a similar evaluation of cytotoxic potency; signifi cant activity was observed


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