Down-Regulation of BAX Gene During Carcinogenesis and Acquisition of Resistance to 5-FU in Colorectal Cancer

Manoochehri, Mehdi; Karbasi, Ashraf; Bandehpour, Mojgan; Kazemi, Bahram

doi:10.1007/s12253-013-9695-0

Cited by 40 publications

(23 citation statements)

References 32 publications

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“…Diverse apoptotic stimuli elevate Bax protein to induce mitochondria‐mediated cell death in oral cancer cells . Low expression of Bax is associated with advanced stage neoplasms, and resistance to chemotherapeutics in colorectal cancer . On the other hand, high expression of Bax is associated with better overall survival and lower recurrence rates in OSCC .…”

Section: Introductionmentioning

confidence: 99%

Role and regulation of proapoptotic Bax in oral squamous cell carcinoma and drug resistance

et al. 2018

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Background: Bax, a proapoptotic protein but its regulation during oral cancer progression and resistance remains elusive. Methods: A total of 127 samples including adjacent normal, primary tumor, and resistance to chemoradiation therapy (RCRT) samples from oral squamous cell carcinoma (OSCC) patients were used. The status of Bax was analyzed at DNA/mRNA/protein levels and the results were correlated with p53 and Akt expression in tissue samples/ cisplatin-resistant oral tongue SCC (SCC9/SCC4-CisR) cell line. Results: Frequent progressive decrease of Bax expression with infrequent promoter methylation, polymorphisms G(-248)A, and mutations was observed in OSCC progression/resistance. Furthermore, by targeting Akt pathway, induction of Bax-dependent cell death was observed and this was further enhanced with nimbolide treatment in SCC9/SCC4-CisR cells. Conclusion: Hence, the Bax gene alteration and its deregulation through p53/Akt pathway are important for OSCC progression and drug resistance. Akt Inhibitor VIII and nimbolide synergistically induce Bax, and it is therefore beneficial for chemosensitizing cisplatin-resistant human OSCC.

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Section: Introductionmentioning

confidence: 99%

Role and regulation of proapoptotic Bax in oral squamous cell carcinoma and drug resistance

et al. 2018

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“…Reduced Bax expression was found to be associated with cisplatin resistance in ovarian carcinoma cells . The Bax gene is downregulated in tumor colorectal cancer cell lines acquiring resistance to 5‐FU compared to wild‐type HT‐29 cells, suggesting that Bax downregulation may serve as a key factor during both colorectal carcinogenesis and cell resistance to 5‐FU . Downregulation of Bax also plays an important role in Zoledronat‐ resistant lung cancer cell lines .…”

Section: Function Of Bax and Its Associated Signalingmentioning

confidence: 99%

Direct Activation of Bax Protein for Cancer Therapy

Liu

Ding

et al. 2015

Medicinal Research Reviews

206

141

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Bax, a central cell death regulator, is an indispensable gateway to mitochondrial dysfunction and a major pro-apoptotic member of the Bcl-2 family proteins that control apoptosis in normal and cancer cells. Dysfunction of apoptosis renders the cancer cell resistant to treatment as well as promotes tumorigenesis. Bax activation induces mitochondrial membrane permeabilization, thereby leading to the release of apoptotic factor cytochrome c and consequently cancer cell death. A number of drugs in clinical use are known to indirectly activate Bax. Intriguingly, recent efforts demonstrate that Bax can serve as a promising direct target for small-molecule drug discovery. Several direct Bax activators have been identified to hold promise for cancer therapy with the advantages of specificity and the potential of overcoming chemo- and radioresistance. Further investigation of this new class of drug candidates will be needed to advance them into the clinic as a novel means to treat cancer.

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“…for example, high-level expression of hent1 correlated with poor clinical response to 5-fu among crc patients (5). BaX downregulation could contribute as an important factor during cell resistance to 5-fu in colon cancer (6). although some progress has been achieved in the past 50 decades, much more efforts are still needed to resolve 5-fu resistance in crc.…”

Section: Introductionmentioning

confidence: 99%

Knockdown of β3GnT8 reverses 5-fluorouracil resistance in human colorectal cancer cells via inhibition the biosynthesis of polylactosamine-type N-glycans

Shen

et al. 2014

International Journal of Oncology

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Abstract. aber rant glycosylation is known to be associated with cancer chemoresistance. β-1,3-n-acetylglucosaminyltransferase (β3gnt)8, which synthesizes polylactosamine on β1-6 branched n-glycans, is dramatically upregulated in colorectal cancer (crc). 5-fluorouracil (5-fu) resistance remains a major obstacle to the chemotherapy of crc. However, little is known with regard to the correlation between 5-fu resistance and the expression of β3gnt8 in crc. in this study, a 5-fu-resistant cell line (SW620/5-fu) was generated, and 50% inhibition concentration (ic50) of 5-fu was determined by Mtt assay. flow cytometry and lectin blot analysis were performed to detect the alteration of polylactosamine structures. Quantitative rt-Pcr and western blot analysis were used to identify and evaluate candidate genes involved in the synthesis of polylactosamine in SW620/5-fu cells. We found polylactosamine chains were significantly increased in SW620/5-fu cells. inhibition of the biosynthesis of polylactosamine by 3'-azidothymidine (aZt) was able to reduce 5-fu tolerance. further studies showed that β3gnt8 expression was also upregulated in 5-fu-resistant cancer cells, and knockdown of β3gnt8 by rna interference reversed 5-fu resistance through, at least partly, by suppressing the formation of polylactosamine. in conclusion, the alteration of β3gnt8 in crc cells correlates with tumor sensitivity to the chemotherapeutic drug and has significant implication for the development of new treatment strategies.

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Down-Regulation of BAX Gene During Carcinogenesis and Acquisition of Resistance to 5-FU in Colorectal Cancer

Cited by 40 publications

References 32 publications

Role and regulation of proapoptotic Bax in oral squamous cell carcinoma and drug resistance

Role and regulation of proapoptotic Bax in oral squamous cell carcinoma and drug resistance

Direct Activation of Bax Protein for Cancer Therapy

Knockdown of β3GnT8 reverses 5-fluorouracil resistance in human colorectal cancer cells via inhibition the biosynthesis of polylactosamine-type N-glycans

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