4-Hydroxybenzoic acid (4-HBA) enhances the sensitivity of human breast cancer cells to adriamycin as a specific HDAC6 inhibitor by promoting HIPK2/p53 pathway

Wang, Xuna; Wang, Kui-Yang; Yang, Chao; Li, Xueying

doi:10.1016/j.bbrc.2018.08.043

Cited by 42 publications

(23 citation statements)

References 31 publications

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“…This result is consistent with a previous study in which HDAC6 selective inhibitor 4-hydroxybenzoic acid failed to induce significant cell death in MCF-7 cells at concentrations below 20 μM (23). On the other hand, several studies demonstrated that HDAC6 inhibition sensitized the antitumor efficacy of chemotherapeutic drugs such as adriamycin and 5-fluorouracil (23,24). In the present study, we found that LYP-2 and LYP-6 enhanced the antiproliferative effect of bortezomib in MCF-7 cells and this combined treatment demonstrated an additive or synergistic effect.…”

Section: Cell Proliferation Inhibitionsupporting

confidence: 64%

Novel HDAC6 selective inhibitors with 4-aminopiperidine-1- carboxamide as the core structure enhanced growth inhibitory activity of bortezomib in MCF-7 cells

Zhao

Gao

Zhang

et al. 2019

BST

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In epigenetics, histone deacetylases (HDACs) are well validated targets for the development of anticancer drugs. In this work, we reported the design and synthesis of a series of twentytwo novel (E)-N-hydroxycinnamamide-based HDAC inhibitors with 4-aminopiperidine-1-carboxamide as the core structure. Most newly synthesized compounds displayed high inhibition rates toward HDAC at the concentration of 1 μM. Among them, the inhibition rates of compounds LYP-2, LYP-3, LYP-6, and LYP-15 were more than 75%. Furthermore, compounds LYP-2, LYP-3, and LYP-6 potently inhibited the activity of HDAC6 with selectivity over HDAC1. We chose LYP-2 and LYP-6 to test its antiproliferative effect on breast cancer cells MCF-7. Either LYP-2 or LYP-6 alone moderately suppressed the cell growth, but could synergistically enhance the inhibitory effect of bortezomib. These results suggested that combined HDAC6 inhibitor and bortezomib regimen might be an option for breast cancer treatment.

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Section: Cell Proliferation Inhibitionsupporting

confidence: 64%

Novel HDAC6 selective inhibitors with 4-aminopiperidine-1- carboxamide as the core structure enhanced growth inhibitory activity of bortezomib in MCF-7 cells

Zhao

Gao

Zhang

et al. 2019

BST

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“…Contrast to the strong enzyme inhibitory activity, our two compounds MH1-18 and MH1-21 showed moderate activity in suppressing the cell proliferation, with IC 50 values more than 40 μM for the four cancer lines. This result is consistent with the low antiproliferative activity of many known selective HDAC6 inhibitors (20,30). For example, in our previous work, we designed and synthesized three novel HDAC6 inhibitors LYP-2, -3, and -6 with the 4-aminopiperidine-1-carboxamide as the core structure which showed moderate efficacy in suppressing the proliferation of cancer cells (20).…”

Section: (Breast Cancer)supporting

confidence: 82%

Design, synthesis and biological evaluation of 4-piperidin-4-yl-triazole derivatives as novel histone deacetylase inhibitors

Gao

Mou

et al. 2019

BST

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Acetylation as one of the most important covalent modification manners in the field of epigenetics, the level of it is taken control of by two families of enzymes with opposite mechanisms, histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDACs are responsible for removal of the acetyl group from lysine residues in histones and non-histone substrates (1). Till now, 18 isoforms of HDACs have been discovered, and they are divided into four categories based on their sequence similarity and functions: class I (HDAC1, 2, Summary Histone deacetylase is an important member of epigenetics and a well validated target for anti-cancer drug discovery. In this study, we designed and synthesized a series of twenty-one novel hydroxamic acid-based histone deacetylase inhibitors with 4-piperidin-4-yl-triazole as the core skeleton. Most target compounds displayed excellent inhibition rates toward histone deacetylases at the concentration of 1 μM. Among them, the inhibition rates of two compounds MH1-18 and MH1-21 exceeded 90%. Furthermore, these two compounds selectively inhibited the activity of histone deacetylase 6 with low IC 50 values. The high potency of them toward histone deacetylase 6 was rationalized by molecular docking studies. We found that MH1-18 and MH1-21 moderately inhibited the proliferation of four human cancer cell lines SGC-7901, NCI-H226, MCF-7, and HL-60. However, MH1-21 showed potent efficacy in suppressing the migration of MCF-7 cells. Results obtained in the current study shed light on designing potent HDAC6 inhibitors as anti-cancer agents.

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“…[46]. 4 HBA also has anticancer activity in the MCF-7 breast cancer and induced apoptosis from the increased of expression of caspase-3 and PARP Cleavage, which was associated with the promotion of p 53 [47]. Treatment of Firulic acid isolated from Ferula Foetida decreased the viability, increased apoptosis, and suppressed the metastatic potential in breast cancer cell line MDA-MD-231 [48].…”

Section: Resultsmentioning

confidence: 98%

Methanol Extract of Coleus amboinicus (Lour) Exhibited Antiproliferative Activity and Induced Programmed Cell Death in Colon Cancer Cell WiDr

Laila

Fardiaz

Yuliana

et al. 2020

International Journal of Food Science

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Coleus amboinicus(Lour) (CA) has been reported to possess many pharmacological activities. In this study, evaluation of cytotoxicity using brine shrimp lethality bioassay and MTT assay using WiDr cell lines was carried out. The expression of several genes responsible for programmed cell death of the methanol extract of CA was also investigated. The morphology of the cells undergoing apoptosis was detected using Hoechst staining assay. The gene expression of BAX, BCL2, P53, Caspase 1, 7, 8, and 9 of treated samples with different concentrations (10, 15, 25 & 50 µg/ml) were measured with RT PCR. The phytochemical profiles were investigated using LC MS. The results showed that the lethality concentration (LC50) of methanol extract using brine shrimp was 34.545 µg/ml and the extract exhibited good antiproliferative activity against cancer cells WiDr with IC50 value (8.598 ± 2.68 µg/ml) as compared to standard drug 5-fluorouracil (IC50 value 1.839 ± 0.03 µg/ml). There was apoptotic evidences from the morphology of treated cells. The expressions of BAX,P53, and Caspase 9 were upregulated in lower concentration of the extract (10 and 15 µg/ml) but downregulated in higher concentration (25 and 50 µg/ml). BCL2 as anti-apoptotic gene was downregulated in all concentrations. Caspase 1 and Caspase 7 were upregulated in high concentration (25 and 50 µg/ml), but downregulated in lower concentrations. These data provide a mode of cell death for the methanol extract of CA in low concentrations corresponding to apoptosis with intrinsic pathway. Many valuable compounds identified including caffeic acid, rosmarinic acid, malic acid, eicosapentanoic acid, benserazide, alpha-linolenic acid, betaine, Salvanolic B, 4-hydroxibenzoic acid and firulic acid have been previously reported as being active agents against many cancer cells. This study suggested that CA might become an effective ingredient for health-beneficial foods to prevent colon cancer.

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4-Hydroxybenzoic acid (4-HBA) enhances the sensitivity of human breast cancer cells to adriamycin as a specific HDAC6 inhibitor by promoting HIPK2/p53 pathway

Cited by 42 publications

References 31 publications

Novel HDAC6 selective inhibitors with 4-aminopiperidine-1- carboxamide as the core structure enhanced growth inhibitory activity of bortezomib in MCF-7 cells

Novel HDAC6 selective inhibitors with 4-aminopiperidine-1- carboxamide as the core structure enhanced growth inhibitory activity of bortezomib in MCF-7 cells

Design, synthesis and biological evaluation of 4-piperidin-4-yl-triazole derivatives as novel histone deacetylase inhibitors

Methanol Extract of Coleus amboinicus (Lour) Exhibited Antiproliferative Activity and Induced Programmed Cell Death in Colon Cancer Cell WiDr

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