Apoptosis induced by ursodeoxycholic acid in human melanoma cells through the mitochondrial pathway

Yu, Hongwei; Fu, Qi‐Rui; Huang, Zhijie; Lin, Jiunn Diann; Chen, Qing‐Xi; Wang, Qin; Shen, Dong‐Yan

doi:10.3892/or.2018.6828

Cited by 16 publications

(21 citation statements)

References 39 publications

(43 reference statements)

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“…Also, anti-proliferative and pro-apoptotic activity of UDCA has been shown in human melanoma M14 cell lines [179]. In M14 cells, UDCA activated the intrinsic pathway of apoptosis and caused G2/M cell cycle arrest.…”

Section: Tudca In Cancermentioning

confidence: 97%

“…In M14 cells, UDCA activated the intrinsic pathway of apoptosis and caused G2/M cell cycle arrest. Simultaneously, UDCA showed little toxicity to normal human cell lines: LO2 hepatocytes and HaCaT keratinocytes [179]. Nevertheless, these results although promising, should be treated with caution since the highly pro-apoptotic potential of UDCA was limited to M14 cells and was not that satisfactory in A375, another melanoma cell line [179].…”

Section: Tudca In Cancermentioning

confidence: 99%

“…Thus, it seems counterintuitive to use chemical chaperones such as TUDCA in cancer research, since their cytoprotective potential would rather benefit in maintaining neoplastic cells instead of eliminating them. Paradoxically, several reports from in-vitro and in-vivo studies inform that TUDCA/UDCA might have some favorable effects in therapy of certain types of cancer [175][176][177][178][179][180][181]. Early studies of the influence of TUDCA on growth of human cholangiocarcinoma Mz-ChA-1 cell line demonstrated that TUDCA suppressed the growth of the Mz-ChA-1 cells due to increased calcium signaling and downstream activation of PKC-α-and MAPK p42/44-dependent pathways [175].…”

Section: Tudca In Cancermentioning

confidence: 99%

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Tauroursodeoxycholate—Bile Acid with Chaperoning Activity: Molecular and Cellular Effects and Therapeutic Perspectives

Kusaczuk

2019

Cells

144

125

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Tauroursodeoxycholic acid (TUDCA) is a naturally occurring hydrophilic bile acid that has been used for centuries in Chinese medicine. Chemically, TUDCA is a taurine conjugate of ursodeoxycholic acid (UDCA), which in contemporary pharmacology is approved by Food and Drug Administration (FDA) for treatment of primary biliary cholangitis. Interestingly, numerous recent studies demonstrate that mechanisms of TUDCA functioning extend beyond hepatobiliary disorders. Thus, TUDCA has been demonstrated to display potential therapeutic benefits in various models of many diseases such as diabetes, obesity, and neurodegenerative diseases, mostly due to its cytoprotective effect. The mechanisms underlying this cytoprotective activity have been mainly attributed to alleviation of endoplasmic reticulum (ER) stress and stabilization of the unfolded protein response (UPR), which contributed to naming TUDCA as a chemical chaperone. Apart from that, TUDCA has also been found to reduce oxidative stress, suppress apoptosis, and decrease inflammation in many in-vitro and in-vivo models of various diseases. The latest research suggests that TUDCA can also play a role as an epigenetic modulator and act as therapeutic agent in certain types of cancer. Nevertheless, despite the massive amount of evidence demonstrating positive effects of TUDCA in pre-clinical studies, there are certain limitations restraining its wide use in patients. Here, molecular and cellular modes of action of TUDCA are described and therapeutic opportunities and limitations of this bile acid are discussed.

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Section: Tudca In Cancermentioning

confidence: 97%

Section: Tudca In Cancermentioning

confidence: 99%

Section: Tudca In Cancermentioning

confidence: 99%

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Tauroursodeoxycholate—Bile Acid with Chaperoning Activity: Molecular and Cellular Effects and Therapeutic Perspectives

Kusaczuk

2019

Cells

144

125

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“…Совсем неожиданной стороной изучения УДХК, этой гидрофильной желчной кислоты с широким спектром биологических функций, явилось недавнее исследование, результаты которого продемонстрировали, что УДХК может эффективно ингибировать пролиферацию двух клеточных линий меланомы человека (M14 и A375), а также зависимость этого эффекта от длительности воздействия и концентрации УДХК [28].…”

Section: роль препаратов урсодезоксихолевой кислотыunclassified

Ursodeoxycholic acid and cancer prevention

Reyzis

2019

Medicinskij sovet

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Along with the great progress in the fight against malignant neoplasms through the improvement of surgical care and the development of chemotherapy, the search for strategies and opportunities to prevent cancer is becoming increasingly important and promising. Early detection and rational treatment of chronic precancerous diseases must be a priority. In this regard, the possible role of ursodeoxycholic acid (UDCA, ursosan, etc.) has been closely studied in recent years. An overview of the role of ursodeoxycholic acid (UDCA) in the prevention of cancer is presented. The pathogenetic basis of this action is the proven normalizing effect of UDCA on bile acid metabolism, microbiome condition and apoptosis. The paper summarizes the latest data on the ability of UDCA to withstand malignization in the liver, throughout the gastrointestinal tract and beyond. These numerous experimental and clinical studies allow us to assert that UDCA drugs, except for the well-known and versatile hepatoprotective effect, can be considered as effective and promising means of cancer prevention throughout the digestive tract and associated organs. Further research into the broad spectrum of UDCA’s ability to prevent gastrointestinal malignization and beyond is reasonable and promising.

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“…The UDCA, derived from the biotransformation of CDCA by intestinal micro ora, is a well-established drug approved for the treatment of primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), with a good safety pro le and minimal side effects even used at high doses [15,16]. Several studies have reported that UDCA exert anti-tumor properties in multiple tumors including melanoma, hepatocellular carcinoma, and colorectal cancer [17][18][19]. However, the preventive effect of UDCA on CRC has been challenged in recent years [20].…”

Section: Introductionmentioning

confidence: 99%

Ursodeoxycholic Acid Suppresses The Malignant Progression of Colorectal Cancer Through TGR5-YAP Axis

Zhang

et al. 2021

Preprint

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Background: The Hippo/YAP pathway plays an important role in the development of cancers. Previous studies have reported that bile acids can activate YAP (Yes Associated Protein) to promote tumorigenesis and tumor progression. Ursodeoxycholic acid (UDCA) is a long-established old drug used for cholestasis treatment. So far, the effect of UDCA on YAP signaling in colorectal cancer (CRC) is not well defined. The study means to explore relationship of UDCA and YAP in CRC.Methods: The effect of UDCA on CRC cells proliferation was examined by MTT and clonogenic assay, western blotting (WB), real-time PCR, seperation of nucleoprotein and cytoplasmic protein and immunofluorescence (IF) assays were used to detect expression of YAP, WB, real-time PCR, GST-pull down assay and rhodamine-labeled phalloidin staining assays were used to detect activity of RhoA. After transfection of YAP5SA plasmids and RhoAV14 plasmids respectively, MTT, clonogenic assay, EdU incorporation assays and WB were performed. WB and ELISA were used to detect activity of cAMP/PKA axis, after blocking cAMP/PKA axis with siRNA and inhibitors, MTT, WB, IF and clonogenic assay were performed to test effect of UDCA on CRC cells. WB, IF and real-time PCR assays were used to detect expression of TGR5 in CRC cells after UDCA treatment, and then TGR5 agonist, TGR5 antagonist and siRNA were used to detect effect of UDCA on CRC cells. AOM/DSS-induced primary model was used to detect effect of UDCA, WB and Immunohistochemistry (IHC) were used to detect expression of related proteins.Results: UDCA suppressed YAP signaling by activating the membrane G‐protein‐coupled bile acid receptor (TGR5). TGR5 mainly regulated cAMP/PKA signaling pathway to inhibit RhoA activity, thereby suppressing YAP signaling. Moreover, the restoration of YAP expression alleviated the inhibitory effect of UDCA on CRC cell proliferation. In AOM/DSS-induced CRC model, UDCA inhibited tumor growth in a concentration-dependent manner and decreased expression of YAP and Ki67.Conclusion: UDCA plays a distinguished role in regulating YAP signaling and CRC growth from the primary bile acids and partial secondary bile acids, demonstrating the importance of maintaining normal intestinal bile acid metabolism in cancer patients. It also presents a potential therapeutic intervention for CRC.

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Apoptosis induced by ursodeoxycholic acid in human melanoma cells through the mitochondrial pathway

Cited by 16 publications

References 39 publications

Tauroursodeoxycholate—Bile Acid with Chaperoning Activity: Molecular and Cellular Effects and Therapeutic Perspectives

Tauroursodeoxycholate—Bile Acid with Chaperoning Activity: Molecular and Cellular Effects and Therapeutic Perspectives

Ursodeoxycholic acid and cancer prevention

Ursodeoxycholic Acid Suppresses The Malignant Progression of Colorectal Cancer Through TGR5-YAP Axis

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