Bitter melon juice targets molecular mechanisms underlying gemcitabine resistance in pancreatic cancer cells

International Journal of Oncology

Volumn 46, Issue 4, 2015, Pages 1849-1857

  Somasagara, Ranganatha R ^a   Deep, Gagan ^a,b   Shrotriya, Sangeeta ^a   Patel, Manisha ^a   Agarwal, Chapla ^a,b   Agarwal, Rajesh ^a,b  

^a UNIVERSITY OF COLORADO   (United States)

^b UNIVERSITY OF COLORADO CANCER CENTER   (United States)

Author keywords

Bitter melon juice; Natural products; Pancreatic cancer

Indexed keywords

2 (2 AMINO 3 METHOXYPHENYL)CHROMONE; 8 [4 (1 AMINOCYCLOBUTYL)PHENYL] 9 PHENYL 1,2,4 TRIAZOLO[3,4 F][1,6]NAPHTHYRIDIN 3(2H) ONE; ADENOSINE TRIPHOSPHATE; GEMCITABINE; GLUCOSE TRANSPORTER 1; GLUCOSE TRANSPORTER 4; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; MOMORDICA CHARANTIA EXTRACT; PROTEIN KINASE B; PROTEIN KINASE B INHIBITOR; UVOMORULIN; ANTINEOPLASTIC AGENT; CADHERIN; DEOXYCYTIDINE; PLANT EXTRACT;

APOPTOSIS; ARTICLE; AUTOPHAGY; CANCER INHIBITION; CANCER RESISTANCE; CANCER SURVIVAL; CELL DEATH; CELL METABOLISM; CELL STRUCTURE; CELL SURVIVAL; CELL VIABILITY; CELLULAR PARAMETERS; CONTROLLED STUDY; DRUG EFFICACY; DRUG MECHANISM; EXTRACELLULAR ACIDIFICATION RATE; GLUCOSE TRANSPORT; GLYCOLYSIS; HUMAN; HUMAN CELL; MOMORDICA CHARANTIA; OXIDATIVE PHOSPHORYLATION; OXYGEN CONSUMPTION RATE; PANCREAS CANCER; PANCREATIC CANCER CELL LINE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; SPINDLE CELL; ANALOGS AND DERIVATIVES; CHEMISTRY; DRUG EFFECTS; DRUG RESISTANCE; GENE EXPRESSION REGULATION; METABOLISM; OXYGEN CONSUMPTION; PANCREATIC NEOPLASMS; TUMOR CELL LINE;

ANTINEOPLASTIC AGENTS; CADHERINS; CELL LINE, TUMOR; CELL SURVIVAL; DEOXYCYTIDINE; DRUG RESISTANCE, NEOPLASM; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; MAP KINASE SIGNALING SYSTEM; MOMORDICA CHARANTIA; OXYGEN CONSUMPTION; PANCREATIC NEOPLASMS; PLANT EXTRACTS;

EID: 84923115597     PISSN: 10196439     EISSN: 17912423     Source Type: Journal    
DOI: 10.3892/ijo.2015.2885     Document Type: Article

References (42)

1. GUILLERMET-GUIBERT J, DAVENNE L, PCHEJETSKI D, SAINT-LAURENT N, BRIZUELA L, GUILBEAU-FRUGIER C, DELISLE MB, CUVILLIER O, SUSINI C and BOUSQUET C: Targeting the sphingolipid metabolism to defeat pancreatic Cancer Cell resistance to the chemothera-peutic gemcitabine drug. Mol Cancer Ther 8: 809-820, 2009.
2. HUANWEN W, ZHIYONG L, XIAOHUA S, XINYU R, KAI W and TONGHUA L: Intrinsic chemoresistance to gemcitabine is associated with constitutive and laminin-induced phosphorylation of faK in pancreatic Cancer Cell lines. Mol Cancer 8: 125, 2009.
3. DI MARCO M, DI CICILIA R, MACCHINI M, NOBILI E, VECCHIARELLI S, BRANDI G and BIASCO G: Metastatic pancreatic cancer: Is gemcitabine still the best standard treatment? (review). Oncol rep 23: 1183-1192, 2010.
4. KAGAWA S, TAKANO S, YOSHITOMI H, et al: Akt/mtor signaling pathway is crucial for gemcitabine resistance induced by Annexin II in pancreatic Cancer cells. J Surg Res 178: 758-767, 2012.
5. SZAKÁCS G, PATERSON JK, LUDWIG JA, BOOTH-GENTHE C and GOTTESMAN MM: Targeting multidrug resistance in cancer. Nat Rev Drug Discov 5: 219-234, 2006.
6. FANCIULLI M, BRUNO T, GIOVANNELLI A, GENTILE F P, DI PADOVA M, RUBIU O and FLORIDI A: Energy metabolism of human loVo colon carcinoma cells: Correlation to drug resistance and infuence of lonidamine. Clin Cancer Res 6: 1590-1597, 2000.
7. ZHOU M, ZHAO Y, DING Y, et al: Warburg effect in chemo-sensitivity: Targeting lactate dehydrogenase-a re-sensitizes taxol-resistant Cancer cells to taxol. Mol Cancer 9: 33, 2010.
8. VIVANCO I and SAWYERS CL: The phosphatidylinositol 3-kinase aKt pathway in human cancer. Nat Rev Cancer 2: 489-501, 2002.
9. TOKUNAGA E, OKI E, EGASHIRA A, SADANAGA N, MORITA M, KAKEJI Y and MAEHARA Y: Deregulation of the akt pathway in human cancer. Curr Cancer Drug targets 8: 27-36, 2008.
10. MCCUBREY JA, STEELMAN LS, CHAPPELL WH, et al: Roles of the raf/MeK/erK pathway in Cell growth, malignant transformation and drug resistance. Biochim Biophys Acta 1773: 1263-1284, 2007.
11. ELSTROM RL, BAUER DE, BUZZAI M, et al: Akt stimulates aerobic glycolysis in Cancer cells. Cancer Res 64: 3892-3899, 2004.
12. GOTTLOB K, MAJEWSKI N, KENNEDY S, KANDEL E, ROBEY RB and HAY N: Inhibition of early apoptotic events by akt/PKB is dependent on the frst committed step of glycolysis and mitochondrial hexokinase. genes Dev 15: 1406-1418, 2001.
13. PLAS DR, TALAPATRA S, EDINGER AL, RATHMELL JC and THOMPSON CB: Akt and Bcl-xl promote growth factor-independent survival through distinct effects on mitochondrial physiology J Biol chem 276: 12041-12048, 2001.
14. MAJEWSKI N, NOGUEIRA V, BHASKAR P, R OY P R, SKEEN JE, GOTTLOB K, CHANDEL NS, THOMPSON CB, ROBEY E B and HAY N: Hexokinase-mitochondria interaction mediated by akt is required to inhibit apoptosis in the presence or absence of Bax and Bak Mol Cell 16: 819-830, 2004
15. HUANG WC and HUNG MC: Induction of akt activity by chemotherapy confers acquired resistance. J formos Med assoc 108: 180-194, 2009
16. DUXBURY MS,. TO H, ZINNER MJ, ASHLEY SW and WHANG EE: Sirna directed against c-Src enhances pancreatic adenocarcinoma Cell gemcitabine chemosensitivity J am coll Surg 198: 953-959, 2004
17. RIBCHOK-ANUN S, ADISAKWATTANA S, YAO CY, SANGVANICH P, ROENGSUMRAN S and HSU WH: Slow acting protein extract from fruit pulp of Momordica charantia with insulin secretagogue and insulinomimetic activities. Biol Pharm Bull 29: 1126-1131, 2006.
18. GANGULY C, DE S and DAS S: Prevention of carcinogen-induced mouse skin papilloma by whole fruit aqueous extract of Momordica charantia. Eur J Cancer Prev 9: 283-288, 2000.
19. CLAFIN AJ, VESELY DL, HUDSON JL, BAGWELL CB, LEHOTAY DC, LO TM, FLETCHER MA, BLOCK NL and LEVEY GS: Inhibition of growth and guanylate cyclase activity of an undifferentiated prostate adenocarcinoma by an extract of the balsam pear (Momordica charantia abbreviata). Proc Natl Acad Sci uSa 75: 989-993, 1978.
20. NAGASAWA H, WATANABE K and INATOMI H: Effects of bitter melon (Momordica charantia l.) or ginger rhizome (Zingiber offfnale rosc) on spontaneous mammary tumorigenesis in SHn mice. Am J chin Med 30: 195-205, 2002.
21. SINGH A, SINGH SP and BAMEZAI R: Momordica charantia (Bitter gourd) peel, pulp, seed and whole fruit extract inhibits mouse skin papillomagenesis. Toxicol Lett 94: 37-46, 1998.
22. WENG JR, BAI LY, CHIU CF, HU JL, CHIU SJ and WU CY: Cucurbitane triterpenoid from Momordica charantia induces apoptosis and autophagy in breast Cancer cells, in part, through peroxisome proliferator-activated receptor γ activation. evid Based complement alternat Med 2013: 935675, 2013.
23. KWATRA D, SUBRAMANIAM D, RAMAMOORTHY P, STANDING D, MORAN E, VELAYUTHAM R, MITRA A, UMAR S and ANANT S: Methanolic extracts of bitter melon inhibit colon Cancer stem cells by affecting energy homeostasis and autophagy. evid Based complement alternat Med 2013: 702869, 2013.
24. HSIAO PC, LIAW CC, HWANG SY, CHENG HL, ZHANG LJ, SHEN CC, HSU FL and KUO CC H: Antiproliferative and hypoglycemic cucur-bitane-type glycosides from the fruits of Momordica charantia. J a gric food chem 61: 2979-2986, 2013.
25. LIMTRAKUL P, KHANTAMAT O and PINTHA K: Inhibition of P-glyco-protein activity and reversal of Cancer multidrug resistance by Momordica charantia extract. Cancer chemother Pharmacol 54: 525-530, 2004
26. KAUR M, DEEP G, JAIN AK, RAINA K, AGARWAL C, WEMPE MF and AGARWAL R: Bitter melon juice activates cellular energy sensor AMP-activated protein kinase causing apoptotic death of human pancreatic carcinoma cells. Carcinogenesis 34: 1585-1592, 2013.
27. AGARWAL C, TYAGI A, KAUR M and AGARWAL R: Silibinin inhibits constitutive activation of Stat3, and causes caspase activation and apoptotic death of human prostate carcinoma Du145 cells. Carcinogenesis 28: 1463-1470, 2007
28. WU M, NEILSON A, SWIFT AL, et al: Multiparameter metabolic analysis reveals a close link between attenuated mitochondrial bioenergetic function and enhanced glycolysis dependency in human tumor cells. Am J Physiol Cell Physiol 292: C125-c136, 2007
29. BRAND MD and NICHOLLS DG: Assessing mitochondrial dysfunction in cells. Biochem J 435: 297-312, 2011.
30. POTTER VR and REIF AE: Inhibition of an electron transport component by antimycin n. J Biol Chem 194: 287-297, 1952.
31. KASUYA K, TSUCHIDA A, NAGAKAWA C, SUZUKI M, ABE Y, ITOI T, SERIZAWA H, NAGAO T, SHIMAZU M and AOKI T: Hypoxia-inducible factor-1α expression and gemcitabine chemotherapy for pancreatic cancer. Oncol rep 26: 1399-1406, 2011.
32. ZHAO Y, BUTLER EB and TAN M: Targeting cellular metabolism to improve Cancer therapeutics. Cell Death Dis 4: E532, 2013.
33. GAO T, FURNARI F and NEWTON AC: PHlPP: A phosphatase that directly dephosphorylates akt, promotes apoptosis, and suppresses tumor growth. Mol Cell 18: 13-24, 2005.
34. GAO AM, KE Z P, SHI F, SUN GC and CHEN H: Chrysin enhances sensitivity of Bel-7402/aDM cells to doxorubicin by suppressing Pi3K/akt/nrf2 and erK/nrf2 pathway. chem Biol interact 206: 100-108, 2013.
35. SIEGEL R, NAISHADHAM D and JEMAL A: Cancer statistics, 2012. ca Cancer J Clin 62: 10-29, 2012.
36. TANG D, OKADA H, RULAND J, LIU L, STAMBOLIC V, MAK TW and INGRAM AJ: Akt is activated in response to an apoptotic signal. J Biol chem 276: 30461-30466, 2001.
37. JEONG EK, LEE SY, JEON HM, JU MK, KIM CH and KANG HS: Role of extracellular signal-regulated kinase (erK)1/2 in multi-cellular resistance to docetaxel in Mcf-7 cells. Int J Oncol 37: 655-661, 2010.
38. MIRMOHAMMADSADEGH A, MOTA R, GUSTRAU A, HASSAN M, NAMBIAR S, MARINI A, BOJAR H, TANNAPFEL A and HENGGE UR: Erk1/2 is highly phosphorylated in melanoma metastases and protects melanoma cells from cisplatin-mediated apoptosis. J Invest Dermatol 127: 2207-2215, 2007.
39. SONG J, QU Z, GUO X, ZHAO Q, ZHAO X, GAO L, SUN K, SHEN F, WU M and WEI L: Hypoxia-induced autophagy contributes to the chemoresistance of hepatocellular carcinoma cells. autophagy 5: 1131-1144, 2009.
40. SUI X, CHEN R, WANG Z, et al: Autophagy and chemotherapy resistance: A promising therapeutic target for Cancer treatment. Cell Death Dis 4: E838, 2013.
41. CAREW JS, NAWROCKI ST, KAHUE CN, ZHANG H, YANG C, CHUNG L, HOUGHTON JA, HUANG P, GILES FJ and CLEVELAND JL: Targeting autophagy augments the Anticancer activity of the histone deacetylase inhibitor SaHa to overcome Bcr-abl-mediated drug resistance. Blood 110: 313-322, 2007.
42. YANG ZJ, CHEE CE, HUANG S and SINICROPE FA: The role of autophagy in cancer: Therapeutic implications. Mol Cancer Ther 10: 1533-1541, 2011.