Andrographolide nanophytosomes exhibit enhanced cellular delivery and pro-apoptotic activities in HepG2 liver cancer cells

Abstract

Andrographolide (AG), a major active constituent of Andrographis paniculata, is known to hinder proliferation of several types of cancer cells. However, its poor solubility and cellular permeability restrict its use in clinical applications. In this study, AG-loaded phytosomes (AG-PTMs) were formulated and optimized with respect to particle size using l -α-phosphatidylcholine (PC):AG ratio and sonication time (ST) as independent variables. The optimized formula was prepared at 1:2.7 for AG:PC molar ratio and 4.9 min for ST and exhibited a particle size of 243.7 ± 7.3 nm, polydispersity index (PDI) of 0.310 and entrapment efficiency of 72.20 ± 4.53. Also, the prepared formula showed a slow release of AG over 24-h period. The antiproliferative activity of AG-PTMs was investigated against the liver cancer cell line HepG2. AG-PTMs significantly repressed the growth of HepG2 cells with an IC 50 value of 4.02 ± 0.14 µM. AG uptake by HepG2 cells was significantly enhanced in incubations containing the optimized formula. AG-PTMs also caused G2-M cell cycle phase arrest and increased the fraction of apoptotic cells in pre-G1 phase. These effects were associated with induction of oxidative stress and mitochondrial dysfunction. In addition, AG-PTMs significantly upregulated mRNA expression of BAX and downregulated that of BCL2. Furthermore, AG-PTMs significantly enhanced the concentration of caspase-3 in comparison to raw AG. These data indicate that the phytosomal delivery of AG significantly inhibited HepG2 cell proliferation through enhanced cellular uptake, arresting cell cycle at the G2-M phase and inducing mitochondrial-dependent apoptosis.

New pyrazolylindolin-2-one based coumarin derivatives as anti-melanoma agents: design, synthesis, dual BRAFV600E/VEGFR-2 inhibition, and computational studies

“…These results are consistent with that reported for sorafenib, which significantly inhibits the growth of cancer cells through the accumulation of cells in the pre-G1 phase. 51…”

“…These results are consistent with that reported for sorafenib, which signicantly inhibits the growth of cancer cells through the accumulation of cells in the pre-G1 phase. 51 These ndings shed light on the mode of action of coumarin derivatives as antiproliferative agents (inducing G0/G1 arrest), which differs from the cytotoxic effect of sorafenib (inducing pre-G1 arrest) and highlight the potential use of coumarins as effective anticancer agents in melanoma treatment. This can be explained by the fact that the G1 phase is a phase that precedes DNA replication, in which the cellular conditions inuence cell cycle progression, causing DNA to either rebuild in a cell or initiate apoptosis, and several studies address the role of G0/G1 phase arrest in intensifying cellular apoptosis.…”

Polyphyllin I attenuates the invasion and metastasis via downregulating GRP78 in drug-resistant hepatocellular carcinoma cells

“…Liver cancer is a major contributor to global cancer-related fatalities, especially in advanced stages with a dismal prognosis. Its high aggressiveness and lethality are often compounded by drug resistance issues [ 25 , 26 ]. Sorafenib, a multikinase inhibitor, has long been the first-line treatment for advanced liver cancer.…”

Inflammation, Mitochondria and Natural Compounds Together in the Circle of Trust

“…In the study by Neamatallah et al, HepG2 cells showed an increased uptake of AG in the phytosomal formulation, resulting in cell cycle arrest in the G2-M phase and increased mitochondrial-dependent apoptosis. Indeed, increased ROS production and decreased MMPs were recorded, as well as an increased expression of Bax and caspase-3 and decreased expression of Bcl-2 [ 132 ].…”