Abnormally high expression of the mammalian de novo lipogenesis (DNL) pathway in various cancer cells promotes cell over-proliferation and resistance to apoptosis. Inhibition key enzymes DNL pathway, namely, ATP citrate lyase, acetyl-CoA carboxylase, fatty acid synthase (FASN) can increase apoptosis without cytotoxicity non-cancerous cells, leading search for presentation novel selective powerful targets therapy. Previous studies reported that epistructured catechins, epigallocatechin...

Calactin, a doubly-linked cardenolide, is commonly found in Apocynaceae family including Calotropis gigantea (L.) Dryand. (Niu jiao gua, C. gigantea). This phytochemical has gained recognition for its potential as an anticancer agent and marker properties. Our previous reports demonstrated the remarkable anti-liver anti-colon cancer activities both vitro vivo of dichloromethane fraction from stem barks (CGD). However, quantitative analysis calactin content CGD by using high-performance...

ABSTRACT Introduction Diterpene lactones in Andrographis paniculata are essential bioactive compounds that contribute to the herb's medicinal properties. The main diterpene A. andrographolide and its derivatives. Spontaneous degradation of leads a short‐term stability casts significant problem storage distribution raw materials products. Objective To determine extracts their transformation dynamics. Materials Methods A 1 H NMR‐based metabolomics workflow HPLC‐based quantitative determination...

The inhibition of the mammalian de novo synthesis long-chain saturated fatty acids (LCFAs) by blocking acid synthase (FASN) enzyme activity in tumor cells that overexpress FASN can promote apoptosis, without apparent cytotoxic to non-tumor cells. present study aimed focus on potent inhibitory effect capsaicin pathway inducing apoptosis HepG2 use as a source for new inhibitor will provide insight into its possible application selective anti-cancer therapy. findings showed promoted well cell...

Conventional chemotherapeutic agents for colorectal cancer (CRC) cause systemic side effects and eventually become less efficacious owing to the development of drug resistance in cells. Therefore, new therapeutic regimens have focused on use natural products. The anticancer activity several parts Calotropis gigantea has been reported; however, its stem bark extract inhibition cell proliferation not yet examined. In this study, C . extract, both alone combination with 5-fluorouracil (5-FU),...

The de novo lipogenesis (DNL) pathway has been identified as a regulator of cancer progression and aggressiveness. Downregulation key enzymes shown to activate apoptosis in cancerous cells. Epigallocatechin gallate (EGCG) inhibits cell proliferation without causing cytotoxicity healthy present study aimed investigate the effects EGCG on promotion associated with DNL inhibition cells, both vitro vivo. We observed that two colorectal lines (HCT116 HT-29) had higher cytotoxic response treatment...

Rationale: The aim of the present study was to assess stability cryopreserved human hepatocytes over 5 years and explore experimental condition-related variables such as seeding density, culture matrix medium, start duration treatment that could potentially affect quality cultures their response cytochrome P450 (CYP) inducers.Results: 63/125 batches were plateable after thawing. Of those, 17 showed reproducible recovery, viability plateability (less than 5% intra-batch variability) up years....

In this paper we report quantitative structure-activity models linking in vivo Drug-Induced Liver Injury (DILI) of organic molecules with some parameters both measured experimentally vitro and calculated theoretically from the molecular structure. At first step, a small database containing information DILI humans was created annotated by observed concerning hepatotoxic effects. Thus, for each compound binary annotation "yes/no" applied to seven endpoints causing different liver pathologies...

Increased expression levels of both mitochondrial citrate transporter (CTP) and plasma membrane (PMCT) proteins have been found in various cancers. The transported citrates by these two provide acetyl-CoA precursors for the de novo lipogenesis (DNL) pathway to support a high rate cancer cell viability development. Inhibition DNL promotes apoptosis without apparent cytotoxic normal cells, leading representation selective powerful targets therapy. present study demonstrates that treatments...

Several fractions of Calotropis gigantea extracts have been proposed to potential anticancer activity in many cancer models. The present study evaluated the C. stem bark liver HepG2 cells and diethylnitrosamine (DEN)-induced primary rats. carcinogenesis model induced by DEN administration has widely used pathophysiological features responses rats that are comparable those seen patients. dichloromethane (CGDCM), ethyl acetate, water obtained from partitioning crude ethanolic extract were...

The cytotoxicity of the ethyl acetate fraction Calotropis gigantea (L.) Dryand. ( C . ) stem bark extract (CGEtOAc) has been demonstrated in many types cancers. This study examined improved cancer therapeutic activity sorafenib when combined with CGEtOAc HepG2 cells. cell viability and migration assays were applied cells treated varying concentrations CGEtOAc, sorafenib, their combination. Flow cytometry was used to determine apoptosis, which corresponded a decline mitochondrial membrane...

Calotropis gigantea stem bark extract, particularly the dichloromethane fraction (CGDCM), demonstrated most potent antiproliferative effects on hepatocellular carcinoma HepG2 and colorectal HCT116 cells. The current study focused enhancing effectiveness of cancer treatment with CGDCM at concentrations close to IC50 in cells by reducing their nutrient supply. (2, 4, 8 μg/mL) for 24 h under glucose conditions 4.5 g/L without fetal bovine serum (FBS) supplementation or starvation (G+/F−), 0 10%...

While higher therapeutic doses of toxic cardiac glycosides derived from Cerbera odollam are frequently employed in cases suicide or homicide, ongoing research is investigating the potential anticancer properties low-concentration extracts obtained fruits C. odollam. The present study aimed to determine enhanced effects and minimize side combining Thailand with sorafenib against HCT116 HepG2 cells. dried powder fresh green was fractionated, its phytochemical contents, including total...

Benzyloxyresorufin-<i>O</i>-dealkylation (BROD) is usually used as a marker of cytochrome P450 (P450) 2B1 in rat. However, some reports show that CYP1A2 also highly implicated. The purpose the present study was to establish bupropion (BUP) hydroxylation, but not BROD, selective vitro CYP2B1 catalytic activity. IC₅₀ for BROD and BUP hydroxylation were equivalent (40.8 ± 4.6 41.8 3.4 μM, respectively) when using liver microsomes from β-naphthoflavone-pretreated rats presence...

The 95% ethanolic extract of the dry powder Calotropis gigantea (C. gigantea) stem bark was separated by fractionation with different solutions to yield 4 fractions: dichloromethane (CGDCM), ethyl acetate (CGEtOAc), and water (CGW). This research focused on CGDCM-induced apoptosis in HepG2 cells IC50 above-IC50 values, which provide useful information for future anticancer applications. CGDCM had lower cytotoxicity normal lung fibroblast IMR-90 than cells. Apoptotic induction mediated...

Suppression of the expression or activities enzymes that are involved in synthesis

Pulmonary arterial hypertension (PAH) is a rare and progressive disease arising from various etiologies pathogenesis. PAH decreases life expectancy due to pulmonary vascular remodeling, elevation of mean pressure, ultimately progresses heart failure. While clinical treatments are available reduce the associated symptoms, complete cure has yet be found. Phosphodiesterase-5 (PDE-5) inhibition been identified as possible intervention point in treatment. The functional vasodilation response...