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Quassinoid analogs exert potent antitumor activity via reversible protein biosynthesis inhibition in human colorectal cancer
Biochem Pharmacol. 2023 Apr 26:115564. doi: 10.1016/j.bcp.2023.115564. Online ahead of print.ABSTRACTCellular protein synthesis is accelerated in human colorectal cancer (CRC), and high expression of protein synthesis regulators in CRC patients is associated with poor prognosis. Thus, inhibition of protein synthesis may be an effective therapeutic strategy for CRC. We previously demonstrated that the quassinoid bruceantinol (BOL) had antitumor activity against CRC. Herein, potent tumor growth suppression (>80%) and STAT3 inhibition was observed in two different mouse models following BOL administration. Loss of body and...
Source: Biochemical Pharmacology - April 28, 2023 Category: Drugs & Pharmacology Authors: Ning Wei James Burnett Desirae L Crocker Yixian Huang Song Li Peter Wipf Edward Chu John C Schmitz Source Type: research

An N6-methyladenosine at the transited codon 273 of p53 pre-mRNA promotes the expression of R273H mutant protein and drug resistance of cancer cells.
This study uncovers a novel function of pre-mRNA m6A as a determinant of mutant protein expression in cancer cells heterozygously carrying the TP53 R273H mutation. Suppressing both RNA methylation and ceramide glycosylation might constitute an efficacious and specific approach for targeting TP53 missense mutations coding for a G>A transition, thereby improving cancer treatments. PMID: 30578766 [PubMed - as supplied by publisher]
Source: Biochemical Pharmacology - December 19, 2018 Category: Drugs & Pharmacology Authors: Uddin MB, Roy KR, Hosain SB, Khiste SK, Hill RA, Jois SD, Zhao Y, Tackett AJ, Liu YY Tags: Biochem Pharmacol Source Type: research

Invited submission to the Diamond Jubilee Special Issue of Biochemical PharmacolLeptin induces SIRT1 expression through activation of NF-E2-related factor 2: implications for obesity-associated colon carcinogenesis.
In conclusion, leptin might play a role in colon carcinogenesis by inducing Nrf2-dependent SIRT1 overexpression. PMID: 29427626 [PubMed - as supplied by publisher]
Source: Biochemical Pharmacology - February 7, 2018 Category: Drugs & Pharmacology Authors: Song NY, Lee YH, Na HK, Baek JH, Surh YJ Tags: Biochem Pharmacol Source Type: research

H2S-induced S-sulfhydration of lactate dehydrogenase A (LDHA) stimulates cellular bioenergetics in HCT116 colon cancer cells.
Abstract Cystathionine-β-synthase (CBS) is upregulated and hydrogen sulfide (H2S) production is increased in colon cancer cells. The functional consequence of this response is stimulation of cellular bioenergetics and tumor growth and proliferation. Lactate dehydrogenase A (LDHA) is also upregulated in various colon cancer cells and has been previously implicated in tumor cell bioenergetics and proliferation. In the present study, we sought to determine the potential interaction between the H2S pathway and LDH activity in the control of bioenergetics and proliferation of colon cancer, using the colon cancer line ...
Source: Biochemical Pharmacology - April 9, 2017 Category: Drugs & Pharmacology Authors: Untereiner AA, Oláh G, Módis K, Hellmich MR, Szabo C Tags: Biochem Pharmacol Source Type: research

Platinum(IV) complex LA-12 exerts higher ability than cisplatin to enhance TRAIL-induced cancer cell apoptosis via stimulation of mitochondrial pathway.
Abstract In search for novel strategies in colon cancer treatment, we investigated the unique ability of platinum(IV) complex LA-12 to efficiently enhance the killing effects of tumor necrosis factor-related apoptosis inducing ligand (TRAIL), and compared it with the sensitizing action of cisplatin. We provide the first evidence that LA-12 primes human colon cancer cells for TRAIL-induced cytotoxicity by p53-independent activation of the mitochondrial apoptotic pathway. The cooperative action of LA-12 and TRAIL was associated with stimulation of Bax/Bak activation, drop of mitochondrial membrane potential, caspase...
Source: Biochemical Pharmacology - October 3, 2014 Category: Drugs & Pharmacology Authors: Jelínková I, Safaříková B, Blanářová OV, Skender B, Hofmanová J, Sova P, Moyer MP, Kozubík A, Kolář Z, Ehrmann J, Vaculová AH Tags: Biochem Pharmacol Source Type: research

Role of Hypoxia Inducible Factor-1α in the Regulation of the Cancer-Specific Variant of Organic Anion Transporting Polypeptide 1B3 (OATP1B3), in Colon and Pancreatic Cancer.
Abstract Organic anion transporting polypeptide 1B3 (OATP1B3) was initially considered to be a liver-specific transporter, mediating the uptake of a variety of endogenous and xenobiotic substances. Over the past decade, several investigations reported that OATP1B3 is also expressed across multiple types of cancers. Only recently, our laboratory and others demonstrated the identity of cancer-specific OATP1B3 variants (csOATP1B3) arising from the use of an alternative transcription initiation site, different from the wildtype (WT) OATP1B3 expressed in the normal liver. However, the mechanisms regulating the expressi...
Source: Biochemical Pharmacology - August 4, 2013 Category: Drugs & Pharmacology Authors: Han S, Kim K, Thakkar N, Kim D, Lee W Tags: Biochem Pharmacol Source Type: research