Honokiol nanomicellar formulation produced increased oral bioavailability and anticancer effects in triple negative breast cancer (TNBC)

Abstract

Triple negative breast cancer (TNBC), owing to its aggressive behavior and toxicity associated with available chemotherapy; currently no suitable therapy is available. Honokiol (HNK) is a promising anticancer drug but has poor bioavailability. In the current study, we evaluated the anticancer effects of an oral Honokiol nanomicellar (NM) formulation (size range of 20–40 nm) in vitro against various TNBC cells lines. Cytotoxicity, clonogenic and wound healing assays demonstrated the promising anticancer effects. In vitro Caco-2 permeability studies suggested increased absorption of Honokiol. Compared to HNK-FD, nanomicellar formulations resulted in significant increase in the oral bioavailability. Cmax (4.06 and 3.60-fold) and AUC (6.26 and 5.83-fold) were significantly increased in comparison to oral 40 and 80 mg/kg free drug respectively. Further, anticancer effects of these formulations were studied in BALB/c nude mice transplanted with orthotopic MDA-MB-231 cell induced xenografts. After 4 weeks of daily administration of HNK-NM formulation, significant reduction in the tumor volumes and weights compared to free drug (p < 0.001) treated groups was observed. Surprisingly, in some of the animals (25%), the treatment resulted in complete eradication of tumors. Increased apoptosis and antiangiogenic effect was observed in HNK-NM groups compared to free drug and untreated control animals. This is the first report demonstrating that HNK-FD possesses anticancer effects against TNBC.

Modulation of cerulein‐induced pancreatic inflammation by hydroalcoholic extract of curry leaf (Murraya koenigii)

“…Immunohistochemistry was performed on 5 μm thick sections after deparaffinisation, as per our previously optimized protocol (Godugu, Doddapaneni, & Singh, ; Khurana, Tekula, & Godugu, ; Tekula et al, ). Sections were subjected to dehydration in graded alcohol followed by washing with Tris buffered saline (TBS) and incubation of the sections with proteinase‐K at 37°C for 20 min.…”

Chemosensitizing Effect of Cernumidine Extracted from Solanum cernuum on Bladder Cancer Cells in Vitro

“…In vitro scratch assay was performed to analyze the percentage inhibition of bridging of migration area by cernumidine and cisplatin alone and in combination. The assay was performed following the protocol described by Godugu and co‐workes . In brief, T24 cells (1.25×10 5 cells/well) were seeded in a 24‐well plate and incubated overnight.…”

“…The assay was performed following the protocol described by Godugu and co-workes. [35] In brief, T24 cells (1.25 × 10 5 cells/well) were seeded in a 24-well plate and incubated overnight. In each well at the middle portion, cells were scratched from the substrate using sterile micropipette tip to make a gap.…”

Honokiol: A Review of Its Anticancer Potential and Mechanisms

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