Investigation of the acetic acid stress response in with mutated H3 residues.

Enhanced levels of acetic acid reduce the activity of yeast strains employed for industrial fermentation-based applications. Therefore, unraveling the genetic factors underlying the regulation of the tolerance and sensitivity of yeast towards acetic acid is imperative for optimising various industrial processes. In this communication, we have attempted to decipher the acetic acid stress response of the previously reported acetic acid-sensitive histone mutants.

Cantharidin downregulates PSD1 expression and inhibits autophagic flux in yeast cells.

Cantharidin is a terpenoid compound of insect origin, naturally produced by male blister beetles as an antipredatory mechanism. Cantharidin has anticancer properties, which are attributed to its ability to induce cell cycle arrest, DNA damage, MAPK signaling pathway, and apoptosis. Cantharidin has been reported to induce apoptosis in triple-negative breast cancer cells by suppressing autophagy via downregulation of Beclin 1 expression and autophagosome formation.

ABC transporter Pdr5 is required for cantharidin resistance in Saccharomyces cerevisiae.

Cantharidin is a potent anti-cancer drug and is known to exert its cytotoxic effects in several cancer cell lines. Although we have ample knowledge about its mode of action, we still know a little about cantharidin associated drug resistance mechanisms which dictates the efficacy and cytotoxic potential of this drug. In this direction, in the present study we employed Sacharomyces cerevisiae as a model organism and screened mutants of pleiotropic drug resistance network of genes for their susceptibility to cantharidin.

Modulation of ruthenium anticancer drugs analogs with tolfenamic acid: Reactivity, biological interactions and growth inhibition of yeast cell.

We synthesized two ruthenium(II) complexes: trans,trans-[Ru(im)(tfa)] (1) and trans,trans‑[Ru(in)(tfa)] (2) where im = 1H‑imidazole, in = 1H‑indazole and tfa = tolfenamic acid, a potential nonsteroidal anti-inflammatory drug (NSAID). The NSAID was opted as bioactive ligand to understand its synergistic therapeutic effect in structurally analogous Ru(II)-compounds with KP418 (imidazolium trans‑[tetrachloridobis(1H‑imidazole)ruthenate(III)]) and KP1019 (indazolium trans‑[tetrachloridobis(1H‑indazole)ruthenate(III)]). The complexes were studied using various analytical methods and structure was determined by X-ray crystallography.

Modifying Chromatin by Histone Tail Clipping.

Post-translational modifications (PTMs) of histone proteins play a crucial role in the regulation of chromatin structure and functions. Studies in the last few decades have revealed the significance of histone PTMs in key cellular processes including DNA replication, repair, transcription, apoptosis and cell cycle regulation. The PTMs on histones are carried out by chromatin modifiers, which are reversible in nature.

A systematic assessment of chemical, genetic, and epigenetic factors influencing the activity of anticancer drug KP1019 (FFC14A).

KP1019 ([trans-RuCl(1H-indazole)]; FFC14A) is one of the promising ruthenium-based anticancer drugs undergoing clinical trials. Despite the pre-clinical and clinical success of KP1019, the mode of action and various factors capable of modulating its effects are largely unknown. Here, we used transcriptomics and genetic screening approaches in budding yeast model and deciphered various genetic targets and plethora of cellular pathways including cellular signaling, metal homeostasis, vacuolar transport, and lipid homeostasis that are primarily targeted by KP1019.