Abstract
Background: Bitter Melon Extract (BME) is widely used for the treatment of various diseases worldwide due to its rich phytochemical and antioxidant content. The well-known anti-cancer drug Paclitaxel (PAC) plays a major role in the treatment of various cancer types such as ovarian, breast, and lung cancer. Technetium-99m (99mTc) radiolabeled paclitaxel is emerging as an imaging probe for breast cancer in vivo. 99mTc labeled compounds have been attracting more scientific attention since the achievement of earlier researches in Nuclear Medicine. People consume several types of diets of plant origin without knowing the interaction with radiolabeled compounds or radiopharmaceuticals.
Objectıve: In the current study, we aimed to monitor the potential effects of the BME on the uptake of 99mTc labeled Paclitaxel (99mTc-PAC) against MCF-7 (ER+) and MDA-MB-231 (ER-) cell lines by using in vitro methods.
Methods: BME was obtained by the extraction of BM seeds by 80% ethanol. PAC was labeled with 99mTc by stannous chloride (SnCl2) as a reducing agent. Cytotoxicity and incorporation assays were performed on MCF-7 and MDA-MB-231 cells within the cell culture studies.
Results: The uptake value of 99mTc-PAC on MCF-7 cells at 240 minutes was 6.20% and BME treated 99mTc- PAC value was 17.39%.
Conclusıon: It is observed that BME treatment has a significant effect on the uptake of 99mTc-PAC on MCF-7 cells which is a known estrogen receptor-positive breast carcinoma cell line. It is concluded that this effect could be due to the estrogen receptor-dependent interaction of BME.
Keywords: Bitter melon extract (BME), technetium-99m (99mTc), Paclitaxel (PAC), MCF-7 (ER+), MDA-MB-231 (ER-) cell lines, estrogen receptor, plant extract interaction.
Graphical Abstract
[1]
Muhammad, N.; Steele, R.; Isbell, T.S.; Philips, N.; Ray, R.B.; Scott Isbell, T.; Philips, N.; Ray, R.B. BITTER MELON EXTRACT INHIBITS BREAST CANCER GROWTH IN PRECLINICAL MODEL BY INDUCING AUTOPHAGIC CELL DEATH. Oncotarget, 2017, 8(39), 66226-66236. [HTTP://DX.DOI.ORG/10.18632/ONCOTARGET.19887]. [PMID: 29029506].
[2]
Olaku, O.; White, J.D. HERBAL THERAPY USE BY CANCER PATIENTS: A LITERATURE REVIEW ON CASE REPORTS. Eur. J. Cancer, 2011, 47(4), 508-514. [HTTP://DX.DOI.ORG/10.1016/J.EJCA.2010.11.018]. [PMID: 21185719].
[3]
Biber Muftuler, F.Z.; Yurt Kilcar, A.; Unak, P. A PERSPECTIVE ON PLANT ORIGIN RADIOLABELED COMPOUNDS, THEIR BIOLOGICAL AFFINITIES AND INTERACTION BETWEEN PLANT EXTRACTS WITH RADIOPHARMACEUTICALS. J. Radioanal. Nucl. Chem., 2015, 306(1), 1-9. [HTTP://DX.DOI.ORG/10.1007/S10967-015-4082-9].
[4]
Barbosa-Filho, J.M.; Alencar, A.A.; Nunes, X.P.; Tomaz, A.C.A.; Sena-Filho, J.G.; Athayde-Filho, P.F.; Silva, M.S.; De Souza, M.F.V.; Da-Cunha, E.V.L. SOURCES OF ALPHA-, BETA-, GAMMA-, DELTA- AND EPSILON-CAROTENES: A TWENTIETH CENTURY REVIEW. Rev. Bras. Farmacogn., 2008, 18(1), 135-154. [HTTP://DX.DOI.ORG/10.1590/S0102-695X2008000100023].
[5]
Bernardo-Filho, M.; Santos-Filho, S.D.; Moura, E.G.; Maiworm, A.I.; Orlando, M.M.C.; Penas, M.E.; Cardoso, V.N.; Bernardo, L.C. 2005.
[7]
Moreno, S.R.F.; Rocha, E.K.; Pereira, M.; Mandarim-Lacerda, C.; Freitas, R.S.; Nascimento, A.L.R.; Carvalho, J.J.; Lima-Filho, G.L.; Dire, G.; Lima, E.A.C. GINKGO BILOBA EXTRACT: EXPERIMENTAL MODEL TO EVALUATE ITS ACTION ON THE LABELING OF BLOOD ELEMENTS WITH TECHNETIUM-99M AND ON THE MORPHOMETRY OF RED BLOOD CELLS. Pak. J. Nutr., 2004, 3, 374-379.
[8]
Nerurkar, P.; Ray, R.B. BITTER MELON: ANTAGONIST TO CANCER. Pharm. Res., 2010, 27(6), 1049-1053. [HTTP://DX.DOI.ORG/10.1007/S11095-010-0057-2]. [PMID: 20198408].
[9]
Pişkin, A.; Altunkaynak, B.Z.; Tümentemur, G.; Kaplan, S.; Yazici, Ö.B.; Hökelek, M. THE BENEFICIAL EFFECTS OF MOMORDICA CHARANTIA (BITTER GOURD) ON WOUND HEALING OF RABBIT SKIN. J. Dermatolog. Treat., 2014, 25(4), 350-357. [HTTP://DX.DOI.ORG/10.3109/09546634.2012.713459]. [PMID: 22812507].
[10]
Dandawate, P.R.; Subramaniam, D.; Padhye, S.B.; Anant, S. BITTER MELON: A PANACEA FOR INFLAMMATION AND CANCER. CH. J. Nat. Med., 2016, 14(2), 81-100. [HTTP://DX.DOI.ORG/10.1016/S1875-5364(16)60002-X].
[11]
Gürlek Kisacik, Ö.; Güneş, Ü.; Yaprakçi, M.V.; Altunbaş, K. EFFECTIVENESS OF BITTER MELON EXTRACT IN THE TREATMENT OF ISCHEMIC WOUNDS IN RATS. Turk. J. Biol., 2018, 42(6), 506-516. [HTTP://DX.DOI.ORG/10.3906/BIY-1804-36]. [PMID: 30983870].
[12]
Wang, P.; Zhu, L.; Sun, D.; Gan, F.; Gao, S.; Yin, Y.; Chen, L. NATURAL PRODUCTS AS MODULATOR OF AUTOPHAGY WITH POTENTIAL CLINICAL PROSPECTS. Apoptosis, 2017, 22(3), 325-356. [HTTP://DX.DOI.ORG/10.1007/S10495-016-1335-1]. [PMID: 27988811].
[13]
Yadav, M.; Lavania, A.; Tomar, R.; Prasad, G.B.K.S.; Jain, S.; Yadav, H. COMPLEMENTARY AND COMPARATIVE STUDY ON HYPOGLYCEMIC AND ANTIHYPERGLYCEMIC ACTIVITY OF VARIOUS EXTRACTS OF EUGENIA JAMBOLANA SEED, MOMORDICA CHARANTIA FRUITS, GYMNEMA SYLVESTRE, AND TRIGONELLA FOENUM GRAECUM SEEDS IN RATS. Appl. Biochem. Biotechnol., 2010, 160(8), 2388-2400. [HTTP://DX.DOI.ORG/10.1007/S12010-009-8799-1]. [PMID: 19904502].
[14]
Jia, S.; Shen, M.; Zhang, F.; Xie, J. RECENT ADVANCES IN MOMORDICA CHARANTIA: FUNCTIONAL COMPONENTS AND BIOLOGICAL ACTIVITIES. Int. J. Mol. Sci., 2017, 18(12), 2555.
[15]
Nagarani, G.; Abirami, A.; Siddhuraju, P. A COMPARATIVE STUDY ON ANTIOXIDANT POTENTIALS, INHIBITORY ACTIVITIES AGAINST KEY ENZYMES RELATED TO METABOLIC SYNDROME, AND ANTI-INFLAMMATORY ACTIVITY OF LEAF EXTRACT FROM DIFFERENT MOMORDICA SPECIES. Food Sci. Hum. Wellness, 2014, 3(1), 36-46. [HTTP://DX.DOI.ORG/10.1016/J.FSHW.2014.02.003].
[16]
Panda, B.C.; Mondal, S.; Devi, K.S.P.; Maiti, T.K.; Khatua, S.; Acharya, K.; Islam, S.S. PECTIC POLYSACCHARIDE FROM THE GREEN FRUITS OF MOMORDICA CHARANTIA (KARELA): STRUCTURAL CHARACTERIZATION AND STUDY OF IMMUNOENHANCING AND ANTIOXIDANT PROPERTIES. Carbohydr. Res., 2015, 401, 24-31. [HTTP://DX.DOI.ORG/10.1016/J.CARRES.2014.10.015]. [PMID: 25464078].
[17]
Raina, K.; Kumar, D.; Agarwal, R. PROMISE OF BITTER MELON (MOMORDICA CHARANTIA) BIOACTIVES IN CANCER PREVENTION AND THERAPY. Semin. Cancer Biol., 2016, 40-41, 116-129. [HTTP://DX.DOI.ORG/10.1016/J.SEMCANCER.2016.07.002]. [PMID: 27452666].
[18]
Mahmoud, M.F.; El Ashry, F.E.Z.Z.; El Maraghy, N.N.; Fahmy, A. STUDIES ON THE ANTIDIABETIC ACTIVITIES OF MOMORDICA CHARANTIA FRUIT JUICE IN STREPTOZOTOCIN-INDUCED DIABETIC RATS. Pharm. Biol., 2017, 55(1), 758-765. [HTTP://DX.DOI.ORG/10.1080/13880209.2016.1275026]. [PMID: 28064559].
[19]
Rashid, M.M.O.; Akhter, K.N.; Chowdhury, J.A.; Hossen, F.; Hussain, M.S.; Hossain, M.T. CHARACTERIZATION OF PHYTOCONSTITUENTS AND EVALUATION OF ANTIMICROBIAL ACTIVITY OF SILVER-EXTRACT NANOPARTICLES SYNTHESIZED FROM MOMORDICA CHARANTIA FRUIT EXTRACT. BMC Complement. Altern. Med., 2017, 17(1), 336. [HTTP://DX.DOI.ORG/10.1186/S12906-017-1843-8]. [PMID: 28651578].
[20]
Saad, D.Y.; Soliman, M.M.; Baiomy, A.A.; Yassin, M.H.; El-Sawy, H.B. EFFECTS OF KARELA (BITTER MELON; MOMORDICA CHARANTIA) ON GENES OF LIPIDS AND CARBOHYDRATES METABOLISM IN EXPERIMENTAL HYPERCHOLESTEROLEMIA: BIOCHEMICAL, MOLECULAR AND HISTOPATHOLOGICAL STUDY. BMC Complement. Altern. Med., 2017, 17(1), 319. [HTTP://DX.DOI.ORG/10.1186/S12906-017-1833-X]. [PMID: 28623919].
[21]
Prashanthi, R.; Mohan, N.; Siva, G. WOUND HEALING PROPERTY OF AQUEOUS EXTRACT OF SEED AND OUTER LAYER OF MOMORDICA CHARANTIA L. ON ALBINO RATS. Indian J. Sci. Technol., 2012, 5(1), 1936-1940. [HTTP://DX.DOI.ORG/10.17485/IJST/2012/V5I1/30961].
[22]
Monteiro, L.O.F.; Fernandes, R.S.; Castro, L.C.; Cardoso, V.N.; Oliveira, M.C.; Townsend, D.M.; Ferretti, A.; Rubello, D.; Leite, E.A.; De Barros, A.L.B. TECHNETIUM-99M RADIOLABELED PACLITAXEL AS AN IMAGING PROBE FOR BREAST CANCER IN VIVO. Biomed. Pharmacother., 2017, 89, 146-151. [HTTP://DX.DOI.ORG/10.1016/J.BIOPHA.2017.02.003]. [PMID: 28222395].
[23]
Siegel, R.L.; Miller, K.D.; Jemal, A. CANCER STATISTICS, 2016. CA Cancer J. Clin., 2016, 66(1), 7-30. [HTTP://DX.DOI.ORG/10.3322/CAAC.21332]. [PMID: 26742998].
[24]
Ray, R.B.; 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. PREVENT. EPIDEMIOL, 2010, 70(5), 1925-1931.
[25]
Vaishampayan, U.; Parchment, R.E.; Jasti, B.R.; Hussain, M. TAXANES: AN OVERVIEW OF THE PHARMACOKINETICS AND PHARMACODYNAMICS. Urology, 1999, 54(6A)(Suppl.), 22-29. [HTTP://DX.DOI.ORG/10.1016/S0090-4295(99)00451-3]. [PMID: 10606281].
[26]
Alaoui, A.E.; Saha, N.; Schmidt, F.; Monneret, C.; Florent, J-C. NEW TAXOL (PACLITAXEL) PRODRUGS DESIGNED FOR ADEPT AND PMT STRATEGIES IN CANCER CHEMOTHERAPY. Bioorg. Med. Chem., 2006, 14(14), 5012-5019. [HTTP://DX.DOI.ORG/10.1016/J.BMC.2006.03.002]. [PMID: 16554162].
[27]
Abraham, S.; Guo, F.; Li, L-S.; Rader, C.; Liu, C.; Barbas, C.F. III; LERNER, R.A.; SINHA, S.C. SYNTHESIS OF THE NEXT-GENERATION THERAPEUTIC ANTIBODIES THAT COMBINE CELL TARGETING AND ANTIBODY-CATALYZED PRODRUG ACTIVATION. Proc. Natl. Acad. Sci. USA, 2007, 104(13), 5584-5589. [HTTP://DX.DOI.ORG/10.1073/PNAS.0700223104]. [PMID: 17372220].
[28]
L.M.; RIONDATO, M.; NADALI, A.; MELE, L.; BANZATO, A.; CAMPORESE, D.; BOCCACCIO, P.; UZUNOV, N.; ROSATO, A.; MAZZI, U. BIOAVAILABILITY OF 99MTC-HA-PACLITAXEL COMPLEX [99MTC-ONCOFID-P] IN MICE USING FOUR DIFFERENT ADMINISTRATION ROUTES. J. Labelled Comp. Radiopharm., 2006, 49, 939-950. [HTTP://DX.DOI.ORG/10.1002/JLCR.1107].
[29]
Aslan, O.; Biber Muftuler, F.Z.; Yurt Kilcar, A.; Ichedef, C.; Unak, P. IN VIVO BIOLOGICAL EVALUATION OF 131 I RADIOLABELED-PACLITAXEL GLUCURONIDE (131 I-PAC-G). Radiochim. Acta, 2012, 100(5), 339-345. [HTTP://DX.DOI.ORG/10.1524/RACT.2012.1922].
[30]
Biber Muftuler, F.Z.; Demir, I.; Ünak, P.; Ichedef, C.; Yurt Kilcar, A. BIOAVAILABILITY OF 99M TC-PACLITAXEL-GLUCURONIDE (99M TC-PAC-G). Radiochim. Acta, 2011, 99(5), 301-306. [HTTP://DX.DOI.ORG/10.1524/RACT.2011.1827].
[31]
Li, C.; Yu, D.F.; Inoue, T.; Yang, D.J.; Tansey, W.; Liu, C.W.; Milas, L.; Hunter, N.R.; Kim, E.E.; Wallace, S. SYNTHESIS, BIODISTRIBUTION AND IMAGING PROPERTIES OF INDIUM-111-DTPA-PACLITAXEL IN MICE BEARING MAMMARY TUMORS. J. Nucl. Med., 1997, 38(7), 1042-1047. [PMID: 9225788].
[34]
Chiampanichayakul, S.; Kataoka, K.; Arimochi, H.; Thumvijit, S.; Kuwahara, T.; Nakayama, H.; Vinitketkumnuen, U.; Ohnishi, Y. INHIBITORY EFFECTS OF BITTER MELON (MOMORDICA CHARANTIA LINN.) ON BACTERIAL MUTAGENESIS AND ABERRANT CRYPT FOCUS FORMATION IN THE RAT COLON. J. Med. Invest., 2001, 48(1-2), 88-96.
[35]
Saeed, F.; Afzaal, M.; Niaz, B.; Arshad, M.U.; Tufail, T.; Hussain, M.B.; Javed, A. BITTER MELON (MOMORDICA CHARANTIA): A NATURAL HEALTHY VEGETABLE. Int. J. Food Prop., 2018, 21(1), 1270-1290. [HTTP://DX.DOI.ORG/10.1080/10942912.2018.1446023].
[36]
Horax, R.; Hettiarachchy, N.; Over, K.; Chen, P.; Gbur, E. EXTRACTION, FRACTIONATION AND CHARACTERIZATION OF BITTER MELON SEED PROTEINS. J. Agric. Food Chem., 2010, 58(3), 1892-1897. [HTTP://DX.DOI.ORG/10.1021/JF902903S]. [PMID: 20052973].
[38]
Santos-Filho, S.D.; Maiworm, A.I.; Presta, G.A.; Paoli, S.; Giani, T.S.; Bernardo-Filho, M. AQUEOUS EXTRACT OF THE MEDICINAL PLANT MENTHA CRISPA ALTERS THE BIODISTRIBUTION OF THE RADIOPHARMACEUTICAL SODIUM PERTECHNETATE IN WISTAR RATS. Med. Chem. Res., 2007, 16(5), 230-237. [HTTP://DX.DOI.ORG/10.1007/S00044-007-9026-7].
[39]
Rocha, G.S.; Pereira, M.O.; Benarroz, M.O.; Frydman, J.N.G.; Rocha, V.C.; Pereira, M.J.; Fonseca, A.S.; Medeiros, A.C.; Bernardo-Filho, M. SUCRALOSE SWEETENER IN VIVO EFFECTS ON BLOOD CONSTITUENTS RADIOLABELING, RED BLOOD CELL MORPHOLOGY AND RADIOPHARMACEUTICAL BIODISTRIBUTION IN RATS. Appl. Radiat. Isot., 2011, 69(1), 46-51. [HTTP://DX.DOI.ORG/10.1016/J.APRADISO.2010.08.009]. [PMID: 20801049].
[40]
Moreno, S.R.F.; Arnobio, A.; De Carvalho, J.J.; Nascimento, L.; Oliveira Timóteo, M.; Olej, B.; Rocha, E.K.; Pereira, M.; Bernardo-Filho, M.; Caldas, L.Q. DE A. THE INGESTION OF A NECTANDRA MEMBRANACEA EXTRACT CHANGES THE BIOAVAILABILITY OF TECHNETIUM-99M RADIOBIOCOMPLEX IN RAT ORGANS. Biol. Res., 2007, 40(2), 131-135. [HTTP://DX.DOI.ORG/10.4067/S0716-97602007000200004]. [PMID: 18064350].
[41]
De, K.; Chandra, S.; Misra, M. EVALUATION OF THE BIOLOGICAL EFFECT OF BRAHMI (BACOPA MONNIERI LINN) EXTRACT ON THE BIODISTRIBUTION OF TECHNETIUM-99M RADIOPHARMACEUTICALS. Life Sci. J., 2008, 5(2), 45-49.
[43]
Hsu, C.; Hsieh, C.L.; Kuo, Y.H.; Huang, C.J. ISOLATION AND IDENTIFICATION OF CUCURBITANE-TYPE TRITERPENOIDS WITH PARTIAL AGONIST/ANTAGONIST POTENTIAL FOR ESTROGEN RECEPTORS FROM MOMORDICA CHARANTIA. J. Agric. Food Chem., 2011, 59(9), 4553-4561. [HTTP://DX.DOI.ORG/10.1021/JF200418G]. [PMID: 21456596].
[44]
Xie, Z.Z.; Li, M.M.; Deng, P.F.; Wang, S.; Wang, L.; Lu, X.P.; Hu, L.B.; Chen, Z.; Jie, H.Y.; Wang, Y.F.; Liu, X.X.; Liu, Z. PARIS SAPONIN-INDUCED AUTOPHAGY PROMOTES BREAST CANCER CELL APOPTOSIS VIA THE AKT/MTOR SIGNALING PATHWAY. Chem. Biol. Interact., 2017, 264, 1-9. [HTTP://DX.DOI.ORG/10.1016/J.CBI.2017.01.004]. [PMID: 28088315].
[45]
Kresty, L.A.; Mallery, S.R.; Stoner, G.D. BLACK RASPBERRIES IN CANCER CLINICAL TRIALS: PAST, PRESENT AND FUTURE. J. Berry Res., 2016, 6(2), 251-261. [HTTP://DX.DOI.ORG/10.3233/JBR-160125]. [PMID: 27594930].
[46]
Moreno, S.R.F.R.F.; Silva, A.L.C.L.C.; Diré, G.; Honeycut, H.; Carvalho, J.J.J.; Nascimento, A.L.L.; Pereira, M.; Rocha, E.K.K.; Oliveira-Timóteo, M.; Arnobio, A.; Olej, B.; Bernardo-Filho, M.; Caldas, L.Q. EFFECT OF ORAL INGESTION OF AN EXTRACT OF THE HERB UNCARIA TOMENTOSA ON THE BIODISTRIBUTION OF SODIUM PERTECHNETATE IN RATS. Braz. J. Med. Biol. Res., 2007, 40(1), 77-80. [HTTP://DX.DOI.ORG/10.1590/S0100-879X2007000100010]. [PMID: 17224999].
[47]
Cekic, B.; Muftuler, F.Z.; Kilcar, A.Y.; Ichedef, C.; Ünak, P. EFFECTS OF BROCCOLI EXTRACT ON BIODISTRIBUTION AND LABELING BLOOD COMPONENTS WITH 99MTC-GH. Acta Cir. Bras., 2011, 26(5), 339-345. [HTTP://DX.DOI.ORG/10.1590/S0102-86502011000500003]. [PMID: 21952655].
[48]
Zora, H.; Muftuler, Z.F.B.; Demir, I.; Yurt Kilcar, A.; Ichedef, C.; Unak, P. EFFECT OF A PLANT ORIGIN DRUG ON THE BIODISTRIBUTION OF 99M TC-DTPA IN WISTAR ALBINO RATS. BRAZILIAN J. PHARMACOGN., 2012, 22(2), 344-349. [HTTP://DX.DOI.ORG/10.1590/S0102-695X2011005000169].
[49]
Sabuncu, B.; Biber Muftuler, F.Z.; Yurt Kilcar, A.; Cekic, B.; Ucar, E.; Unak, P. INTERACTION BETWEEN GREEN TEA EXTRACT AND 99MTC-PERTECHNETATE ON IN VIVO DISTRIBUTION. J. Radioanal. Nucl. Chem., 2014, 300(3), 1021-1026. [HTTP://DX.DOI.ORG/10.1007/S10967-014-3089-Y].
[50]
Uçar, E.; Teksöz, S.; İçhedef, Ç.; Kilçar, A.Y.; Ünak, P. EFFECT OF ROSEMARY (ROSMARINUS OFFICINALIS) EXTRACT ON THE BIODISTRIBUTION OF 99M TC SULPHUR COLLOID AND ON THE RADIOLABELED BLOOD CONSTITUENTS. BRAZILIAN J. PHARMACOGN., 2013, 23(1), 182-185. [HTTP://DX.DOI.ORG/10.1590/S0102-695X2012005000148].
Related Journals
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
Current Bioactive Compounds
Current Cancer Drug Targets
Current Cancer Therapy Reviews
Current Drug Safety
Current Drug Targets
Recent Patents on Anti-Cancer Drug Discovery
Letters in Drug Design & Discovery
Current Drug Discovery Technologies
Current Radiopharmaceuticals
Related Books
Science of Spices and Culinary Herbs - Latest Laboratory, Pre-clinical, and Clinical Studies
Frontiers in Clinical Drug Research - Anti-Cancer Agents
Advances in Organic Synthesis
Frontiers in Natural Product Chemistry
Recent Advances in Analytical Techniques
Frontiers in Drug Design and Discovery
NEOPLASIA and FERTILITY
Therapeutic Use of Plant Secondary Metabolites
Frontiers in Computational Chemistry
Frontiers in Bioactive Compounds
Article Metrics
12