Potent effect of 5‐HPBR, a butanoate derivative of 4‐HPR, on cell growth and apoptosis in cancer cells

Han, Han; Kwon, Youn-Ja; Park, Si-Ho; Kim, Eun-Joo; Rho, Young-Soy; Sin, Hong‐Sig; Um, Soo‐Jong

doi:10.1002/ijc.11643

Cited by 9 publications

(3 citation statements)

References 26 publications

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“…In ACC, we found that five metabolic signaling pathways enriched in low-TMB group (Table 2 ). Among that, butanoate has served as an anticancer ingredient [ 20 ], and its metabolism pathway has been found to be disrupted in breast cancer patients [ 21 ]. Therefore, butanoate metabolism has been regarded as an approach to differentiate cancer patients from healthy individuals [ 21 ].…”

Section: Resultsmentioning

confidence: 99%

Tumor mutational burden presents limiting effects on predicting the efficacy of immune checkpoint inhibitors and prognostic assessment in adrenocortical carcinoma

Guan

Zhang

et al. 2022

BMC Endocr Disord

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Background Adrenocortical carcinoma (ACC) is a highly malignant urologic cancer and tends to metastasize. Although immune checkpoint inhibitors (ICIs) bring a glimmer of light to conquer ACC, only a fraction of patients have benefit from ICIs treatment. It is well known that tumor mutational burden (TMB) is closely associated with the efficacy and response rate of immunotherapy. However, its roles in ACC were not investigated. Methods Using somatic mutations data of 92 ACC samples in TCGA database, we calculated their TMB values by the ‘maftools’ package in R software (Ver 3.6.3). To explore the roles of TMB in ICIs therapy, we have addressed this issue from three perspectives. First, the effects of TMB levels on tumor immune microenvironment (TIM) were analyzed through CIBERSORT algorithm, ssGSEA method and TIMER web server. Second, we investigated the expressive correlations between TMB level and five pivotal immune checkpoints based on Pearson coefficient. Third, the difference in TIDE score between high- and low-TMB groups was compared. The prognostic value of TMB was also evaluated. Besides, GSEA was performed to determine the changes in the activities of signaling pathways caused by TMB. Results TMB values in ACC samples were not high. The average of total mutation counts in each sample was only 21.5. High TMB could lead metabolic reprogramming and poor survival outcomes. However, it was unable to affect the infiltration levels of lymphocytes, and failed to facilitate the activities of immune-related pathways. Regarding immune checkpoints (ICs), only PD-L1 upregulation could result in a good prognosis, and TMB level did not correlate with the expressions of other ICs except for LAG3. There was no significant difference in TIDE score between high- and low-TMB groups. Combining the present results and previous study, we speculated that inadequate stimulation for neoantigens formation, intrinsic immune-resistance and special genomic alterations were three possible reasons for TMB limiting functions in TIM and ICIs. Besides, TMB was toughly applied in clinical practice due to its high cost of determination and non-universal definition of high TMB. Conclusions TMB presents limiting effects on prediction for ICIs efficacy and prognostic assessment for ACC patients.

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Section: Resultsmentioning

confidence: 99%

Tumor mutational burden presents limiting effects on predicting the efficacy of immune checkpoint inhibitors and prognostic assessment in adrenocortical carcinoma

Guan

Zhang

et al. 2022

BMC Endocr Disord

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“…However, cleavages of caspases 3 and 8 were evident in PLC/PRF/5 and CaSki cells. 36 Activation of caspase 3 was observed within 6 h after treatment of HL-60 cells with kinetin riboside. 3 For HepG2 cells, treatment with different doses of kinetin riboside had resulted in cell death but not the activation of active caspase 3.…”

Section: Discussionmentioning

confidence: 98%

Inhibitory effect of kinetin riboside in human heptamoa, HepG2

et al. 2009

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Cytokinins ribosides such as kinetin riboside are a class of plant hormone that were first identified as factors that promote cell division and have since been implicated in many other aspects of plant growth and development. From the data obtained from cell cycle analysis with flow cytometry, the in vitro growth inhibition of human heptamoa, HepG2 cells with kinetin riboside was mediated by causing G2/M cell cycle arrest and cell death. At the same time, treatment with various doses of kinetin riboside in HepG2 cells did not result in a population of cells positive for the active caspase 3. Differentially expressed proteins in the mitochondria of HepG2 cells with cell death induced by kinetin riboside were investigated. Without the use of stable isotope labeling, the proposed method using LC/MSMS provided a rapid approach to study the differentially expressed proteins in the mitochondria due to the cell death induced by kinetin riboside in HepG2 cells. The ability of kinetin riboside to induce cell death and attenuate G1 to S transition is probably a consequence of its ability to interfere with several components in the mitochondria. Hence, it was proposed that the cell death caused by kinetin riboside in HepG2 cells affected a network of proteins involved in cell death and electron transport.

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“…The potent inhibitory effect of 5-HPBR was suggested to be mediated by apoptosis but the exact mechanism appears to differ among cancer cell types. 11 Another example of a bioactive butanoate derivative is the novel bioactive compound, 3-hydroxy, 2-methoxy-sodium butanoate, isolated from the leaves of Clerodendrum phlomidis. This compound displayed considerably potent anti-inflammatory and anti-arthritic effects.…”

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confidence: 99%