Bitter Taste Receptors Are Expressed in Human Epithelial Ovarian and Prostate Cancers Cells and Noscapine Stimulation Impacts Cell Survival

Overview

Journal Mol Cell Biochem

Publisher Springer

Specialty Biochemistry

Date 2018 Oct 24

PMID 30350307

Citations 37

Authors

Louis T P Martin

Mark W Nachtigal

Tamara Selman

Elaine Nguyen

Jayme Salsman

Graham Dellaire

Denis J Dupre

Affiliations

Soon will be listed here.

Abstract

Bitter taste receptors (Tas2Rs) are a subfamily of G-protein coupled receptors expressed not only in the oral cavity but also in several extra-oral tissues and disease states. Several natural bitter compounds from plants, such as bitter melon extract and noscapine, have displayed anti-cancer effects against various cancer types. In this study, we examined the prevalence of Tas2R subtype expression in several epithelial ovarian or prostate cancer cell lines, and the functionality of Tas2R14 was determined. qPCR analysis of five TAS2Rs demonstrated that mRNA expression often varies greatly in cancer cells in comparison to normal tissue. Using receptor-specific siRNAs, we also demonstrated that noscapine stimulation of ovarian cancer cells increased apoptosis in ovarian cancer cells in a receptor-dependent, but ROS-independent manner. This study furthers our understanding of the function of Tas2Rs in ovarian cancer by demonstrating that their activation has an impact on cell survival.

Citing Articles

A deadly taste: linking bitter taste receptors and apoptosis.

Miller Z, Carey R, Lee R Apoptosis. 2025; .

PMID: 39979526 DOI: 10.1007/s10495-025-02091-3.

Agonist activation to open the Gα subunit of the GPCR-G protein precoupled complex defines functional agonist activation of TAS2R5.

Yang M, Duy Mac K, Strzelinski H, Hoffman S, Kim D, Kim S Proc Natl Acad Sci U S A. 2024; 121(48):e2409987121.

PMID: 39565310 PMC: 11621838. DOI: 10.1073/pnas.2409987121.

Molecular interplay between the upregulated levels of Sad1 and UNC84 Domain Containing 2 (SUN2) and gene expression in medulloblastoma cells.

Tecalco-Cruz A, Macias-Silva M, Sosa-Garrocho M, Poot-Hernandez A, Peralta-Alvarez C, Ramirez-Jarquin J Mol Biol Rep. 2024; 51(1):1164.

PMID: 39560853 DOI: 10.1007/s11033-024-10078-7.

Extragustatory bitter taste receptors in head and neck health and disease.

Harris J, Lee R, Carey R J Mol Med (Berl). 2024; 102(12):1413-1424.

PMID: 39317733 PMC: 11579162. DOI: 10.1007/s00109-024-02490-0.

Noscapine and Apoptosis in Breast and Other Cancers.

Calaf G, Crispin L, Quisbert-Valenzuela E Int J Mol Sci. 2024; 25(6).

PMID: 38542508 PMC: 10970989. DOI: 10.3390/ijms25063536.

References

Chandrashekar J, Mueller K, Hoon M, ADLER E, Feng L, Guo W . T2Rs function as bitter taste receptors. Cell. 2000; 100(6):703-11. DOI: 10.1016/s0092-8674(00)80706-0. View

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

Zhou J, Gupta K, Yao J, Ye K, Panda D, Giannakakou P . Paclitaxel-resistant human ovarian cancer cells undergo c-Jun NH2-terminal kinase-mediated apoptosis in response to noscapine. J Biol Chem. 2002; 277(42):39777-85. DOI: 10.1074/jbc.M203927200. View

Aneja R, Vangapandu S, Lopus M, Chandra R, Panda D, Joshi H . Development of a novel nitro-derivative of noscapine for the potential treatment of drug-resistant ovarian cancer and T-cell lymphoma. Mol Pharmacol. 2006; 69(6):1801-9. DOI: 10.1124/mol.105.021899. View

Aneja R, Dhiman N, Idnani J, Awasthi A, Arora S, Chandra R . Preclinical pharmacokinetics and bioavailability of noscapine, a tubulin-binding anticancer agent. Cancer Chemother Pharmacol. 2007; 60(6):831-9. DOI: 10.1007/s00280-007-0430-y. View

Schmittgen T, Livak K . Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008; 3(6):1101-8. DOI: 10.1038/nprot.2008.73. View

Barken I, Geller J, Rogosnitzky M . Noscapine inhibits human prostate cancer progression and metastasis in a mouse model. Anticancer Res. 2009; 28(6A):3701-4. View

Kurman R, Shih I . The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory. Am J Surg Pathol. 2010; 34(3):433-43. PMC: 2841791. DOI: 10.1097/PAS.0b013e3181cf3d79. View

Ray R, Raychoudhuri A, Steele R, Nerurkar P . Bitter melon (Momordica charantia) extract inhibits breast cancer cell proliferation by modulating cell cycle regulatory genes and promotes apoptosis. Cancer Res. 2010; 70(5):1925-31. DOI: 10.1158/0008-5472.CAN-09-3438. View

10.

Sung B, Ahn K, Aggarwal B . Noscapine, a benzylisoquinoline alkaloid, sensitizes leukemic cells to chemotherapeutic agents and cytokines by modulating the NF-kappaB signaling pathway. Cancer Res. 2010; 70(8):3259-68. PMC: 2855771. DOI: 10.1158/0008-5472.CAN-09-4230. View

11.

Chougule M, Patel A, Sachdeva P, Jackson T, Singh M . Anticancer activity of Noscapine, an opioid alkaloid in combination with Cisplatin in human non-small cell lung cancer. Lung Cancer. 2010; 71(3):271-82. PMC: 3094914. DOI: 10.1016/j.lungcan.2010.06.002. View

12.

Deshpande D, Wang W, McIlmoyle E, Robinett K, Schillinger R, An S . Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction. Nat Med. 2010; 16(11):1299-304. PMC: 3066567. DOI: 10.1038/nm.2237. View

13.

Singh N, Vrontakis M, Parkinson F, Chelikani P . Functional bitter taste receptors are expressed in brain cells. Biochem Biophys Res Commun. 2011; 406(1):146-51. DOI: 10.1016/j.bbrc.2011.02.016. View

14.

Ferlay J, Shin H, Bray F, Forman D, Mathers C, Parkin D . Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2011; 127(12):2893-917. DOI: 10.1002/ijc.25516. View

15.

Su W, Huang L, Ao Q, Zhang Q, Tian X, Fang Y . Noscapine sensitizes chemoresistant ovarian cancer cells to cisplatin through inhibition of HIF-1α. Cancer Lett. 2011; 305(1):94-9. DOI: 10.1016/j.canlet.2011.02.031. View

16.

Chougule M, Patel A, Jackson T, Singh M . Antitumor activity of Noscapine in combination with Doxorubicin in triple negative breast cancer. PLoS One. 2011; 6(3):e17733. PMC: 3057970. DOI: 10.1371/journal.pone.0017733. View

17.

Carrai M, Steinke V, Vodicka P, Pardini B, Rahner N, Holinski-Feder E . Association between TAS2R38 gene polymorphisms and colorectal cancer risk: a case-control study in two independent populations of Caucasian origin. PLoS One. 2011; 6(6):e20464. PMC: 3107225. DOI: 10.1371/journal.pone.0020464. View

18.

Ru P, Steele R, Nerurkar P, Phillips N, Ray R . Bitter melon extract impairs prostate cancer cell-cycle progression and delays prostatic intraepithelial neoplasia in TRAMP model. Cancer Prev Res (Phila). 2011; 4(12):2122-30. PMC: 3232292. DOI: 10.1158/1940-6207.CAPR-11-0376. View

19.

Chougule M, Patel A, Sachdeva P, Jackson T, Singh M . Enhanced anticancer activity of gemcitabine in combination with noscapine via antiangiogenic and apoptotic pathway against non-small cell lung cancer. PLoS One. 2011; 6(11):e27394. PMC: 3216931. DOI: 10.1371/journal.pone.0027394. View

20.

Li F . Taste perception: from the tongue to the testis. Mol Hum Reprod. 2013; 19(6):349-60. DOI: 10.1093/molehr/gat009. View