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Anticarcinogenic Properties of Piper longum Linn Extract in Combination with 5-Fluorouracil Chemotherapeutic Drug in Colon (DLD1) and Breast (MDA-MB-231) Cancer Cell Lines: Piper longum L. Exhibits Anticarcinogenic Effects in Both Cancer Cell Lines

Yıl 2025, Cilt: 15 Sayı: 3, 349 - 358, 05.01.2026

Öz

Aim: Piper longum Linn (Piper longum L.) is a mostly used plant in conventional medicine and is well-known for various biological effects. This study investigated the anticancer effects of the extract obtained from P. longum L. on breast and colon cancer cells.
Material and Methods: DLD1 colon and MDA-MB-231 breast cancer and mouse fibroblast L929 as healthy cell line models were treated with Piper longum L. extract at concentrations of 50 μg/ mL, 100 μg/mL and 200 μg/mL. Piper longum L. was also treated in combination with a chemotherapeutic drug, 5-Fluorouracil. The anticancer effects were evaluated using cell viability, apoptotic index, and colony formation assays. In addition, FOXM1, an important transcription factor related to cell proliferation and metastasis, and SIRT2 protein expression were examined, as they are recognized to have both oncogenic and tumour suppressor roles. In addition, SIRT3, which contributes to energy metabolism and cellular homeostasis, and PDH protein levels, which support mitochondrial energy production by converting glycolysis into acetyl-CoA, were analyzed.
Results: The experiments showed that Piper longum L. extract had low cytotoxic effects on L929 cells but significantly reduced cell viability in colon and breast cancer cell lines. Additionally, extract treatment inhibited colony formation and slowed cell proliferation in the tested cell lines. Increased PDH expression and the presence of apoptosis suggest that energy metabolism is targeted, especially in MDA-MB-231 cells. The experiment with the DLD1 cell line indicates that decreased FOXM1 expression reduces cell proliferation.
Conclusion: This study reveals, under in vitro conditions, the antiproliferative and pro-apoptotic effects of Piper longum L. on colon and breast cancer cells, as well as its effects on metabolic pathways.

Kaynakça

  • 1. Hausman, DM. What Is Cancer? Perspectives in Biology and Medicine 2019:62(4):778–784.
  • 2. Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA. et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747–752.
  • 3. Rossi L, Mazzara C, Pagani O. Diagnosis and Treatment of Breast Cancer in Young Women. Current Treatment Options in Oncology. 2019;20(12):86.
  • 4. Bitar SA., El-Sabban M, Doughan S, Abou-Kheir, W. Molecular mechanisms targeting drug-resistance and metastasis in colorectal cancer: Updates and beyond. World Journal of Gastroenterology. 2023;29(9):1395–1426.
  • 5. Zhu G, Pei L, Xia H, Tang Q, Bi F. Role of oncogenic KRAS in the prognosis, diagnosis and treatment of colorectal cancer. Molecular Cancer. 2021;20(1):143.
  • 6. Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, et al. Global Cancer Observatory: Cancer Today. Lyon: International Agency for Research on Cancer. 2020; (https://gco.iarc.fr/ today (Accessed February 2021).
  • 7. de Martel C, Georges D, Bray F, Ferlay J, Clifford GM. Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis. Lancet Glob Health. 2020;8(2):e180–e190.
  • 8. Biswas P, Ghorai M, Mishra T, Gopalakrishnan AV, Roy D, Mane AB, et al. Piper longum L.: A comprehensive review on traditional uses, phytochemistry, pharmacology, and health‐promoting activities. Phytotherapy Research. 2022;36(12):4425–4476.
  • 9. Zaveri M, Khandhar A, Patel S, Patel A. Chemistry and pharmacology of Piper longum L. International journal of pharmaceutical sciences review and research. 2010;5(1):67–76.
  • 10. Chanchal C, Thongam B, Handique PJ. Morphological diversity and characterization of some of the wild Piper species of North East India. Genetic Resources and Crop Evolution. 2015;62:303–313.
  • 11. Yadav V, Krishnan A, Vohora DA. systematic review on Piper longum L.: Bridging traditional knowledge and pharmacological evidence for future translational research. Journal of Ethnopharmacology. 2020;247, 112255.
  • 12. Kumar S, Kamboj J, Suman, Sunil Sharma S. Overview for Various Aspects of the Health Benefits of Piper Longum Linn. Fruit. J Acupunct Meridian Stud. 2011;4(2):134−140.
  • 13. Wang Y, Wang J. W., X. Xiao, Y. Shan, B. Xue, G. Jiang, Q. He, J. Chen, H. G. Xu, R. X. Zhao, K. D. Werle, R. Cui, J. Liang, Y. L. Li, Z. X. Xu. (2013). Piperlongumine induces autophagy by targeting p38 signaling. Cell Death Dis. 2013;4(2013):e824.
  • 14. Patel K, Chowdhury N, Doddapaneni R, Boakye C, Godugu C, Singh M. Piperlongumine for Enhancing Oral Bioavailability and Cytotoxicity of Docetaxel in Triple-Negative Breast Cancer. Journal of pharmaceutical sciences. 2015;104(12):4417–4426.
  • 15. Basak D, Punganuru SR., Srivenugopal KS. Piperlongumine exerts cytotoxic effects against cancer cells with mutant p53 proteins at least in part by restoring the biological functions of the tumor suppressor. Int. J. Oncol. 2016;48(2016):1426–1436.
  • 16. Park JA, Na HH, Jin HO, Kim KC. Increased Expression of FosB through Reactive Oxygen Species Accumulation Functions as Pro-Apoptotic Protein in Piperlongumine Treated MCF7 Breast Cancer Cells. Mol Cells. 2019; 31;42(12):884–892.
  • 17. Kumar S, Agnihotri N. Piperlongumine targets NF-κB and its downstream signaling pathways to suppress tumor growth and metastatic potential in experimental colon cancer. Mol Cell Biochem. 2021;476:1765–1781.
  • 18. Awasthee N, Shekher, A, Rai, Verma SS, Mishra S, Dhasmana A, Gupta SC. Piperlongumine, a piper alkaloid, enhances the efficacy of doxorubicin in breast cancer: Involvement of glucose import, ROS, NF-κB and lncRNAs. Apoptosis: An International Journal on Programmed Cell Death. 2022;27(3-4):261–282.
  • 19. Longley DB, Harkin DP, Johnston PG. 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003;3(5):330–8.
  • 20. Yildiz B, Demirel R, Havadar HB, Yildiz G, Öziç C, Kamiloğlu NN, et al. Blocking SIG1R Along with Low Cadmium Exposure Display Anti-cancer Qualities in Both MCF7 and MDA-MB-231 Cells. Biological Trace Element Research. 2023;202:3588–3600.
  • 21. Ribble D, Goldstein NB, Norris DA, Shellman YG. A simple technique for quantifying apoptosis in 96-well plates. BMC Biotechnol. 2005;5:12.
  • 22. Ozden O, Park SH, Wagner BA, Yong Song H, Zhu Y, Vassilopoulos A, et al. SIRT3 deacetylates and increases pyruvate dehydrogenase activity in cancer cells. Free Radical Biology and Medicine. 2014;76:163–172.
  • 23. Sharma D, Kapri A, Kumar S, Shiri T. Review on Anti-tumor activity, Immunomodulatory and neuromodulatory properties of Piper longum Linn. Journal of Ayurvedic and Herbal Medicine. 2022;8(1):55–60.
  • 24. Sinha A, Patel AS, Kamal P, Patel S, Srivastava A, Kumar S, Tiwari DM. Therapeutic Potential of Piper longum: A Review of Piperine and Piperlongumine in Human Health. Journal of Neonatal Surgery,. 2025;14(19).
  • 25. Fujihashi Y, Jo Kim M, Maneenet J, Awale S. (2023). Piper longum Constituents Induce PANC-1 Human Pancreatic Cancer Cell Death under Nutrition Starvation. Chemistry & Biodiversity. 2023;20(9):e202300280.
  • 26. Tripathi SK, Biswal BK. Piperlongumine, a potent anticancer phytotherapeutic: Perspectives on contemporary status and future possibilities as an anticancer agent. Pharmacological Research. 2020;156:104772.
  • 27. Turrini E, Sestili P, Fimognari C. Overview of the Anticancer Potential of the “King of Spices” Piper nigrum and Its Main Constituent Piperine. Toxins. 2020;12(12):747.
  • 28. Wan Q, Xu J, Zhu C, Liu X, Tu Y, Lei J, Yu J. Alkaloids from Piper longum Exhibit Anti-inflammatory Activity and Synergistic Effects with Chemotherapeutic Agents against Cervical Cancer Cells. J Agric Food Chem. 2023;Jul 12;71(27):10349–10360.
  • 29. Jeon SJ, Choi EY, Han EJ, Lee SW, Moon JM, Jung SH, et al. Piperlongumine induces apoptosis via the MAPK pathway and ERK-mediated autophagy in human melanoma cells. International Journal of Molecular Medicine. 2023;52(6):1–11
  • 30. Ovadje P, Ma D, Tremblay P, Roma A, Steckle M, Guerrero JA, et al. Evaluation of the Efficacy & Biochemical Mechanism of Cell Death Induction by Piper longum Extract Selectively in InVitro and In-Vivo Models of Human Cancer Cells. PLos One. 2014;9(11):e113250.
  • 31. Wang H, Wang Y, Gao H, Wang B, Dou L, Li Y. Piperlongumine induces apoptosis and autophagy in leukemic cells through targeting the PI3K/Akt/mTOR and p38 signaling pathways. Oncology Letters. 2018;15(2):1423–1428.
  • 32. Kung FP, Lim YP, Chao WY, Zhang YS, Yu HI, Tai TS, et al. Piperlongumine, a Potent Anticancer Phytotherapeutic, Induces Cell Cycle Arrest and Apoptosis In Vitro and In Vivo through the ROS/Akt Pathway in Human Thyroid Cancer Cells. Cancers. 2021;13(17):4266.
  • 33. Brix N, Samaga D, Hennel R, Gehr K, Zitzelsberger H, Lauber K. The clonogenic assay: Robustness of plating efficiencybased analysis is strongly compromised by cellular cooperation. Radiation Oncology. 2020;15(1):248.
  • 34. Franken NAP, Rodermond HM, Stap J, Haveman J, van Bree C. Clonogenic assay of cells in vitro. Nature Protocols. 2006;1(5):2315–2319.
  • 35. Lau TS, Chan LKY, Wong ECH, Hui CWC, Sneddon K, Cheung TH, et al. A loop of cancer-stroma-cancer interaction promotes peritoneal metastasis of ovarian cancer via TNFαTGFα-EGFR. Oncogene. 2017;36(25):3576–3587.
  • 36. Yildiz B, Demirel R, Staudacher JJ, Beseren H, Yildiz G, Akpinar AE, et al. SIRT2 deacetylates and decreases the expression of FOXM1 in colon cancer. Journal of Biochemical and Molecular Toxicology. 2024;38(11):e70018.
  • 37. Finley LWS, Carracedo A, Lee J, Souza A, Egia A, Zhang J, et al. SIRT3 Opposes Reprogramming of Cancer Cell Metabolism through HIF1α Destabilization. Cancer Cell. 2011;19(3):416–428.
  • 38. Haigis MC, Deng CX, Finley LWS, Kim HS, Gius D. SIRT3 is a mitochondrial tumor suppressor: A scientific tale that connects aberrant cellular ROS, the Warburg effect, and carcinogenesis. Cancer Research. 2012;72(10):2468–2472

Yıl 2025, Cilt: 15 Sayı: 3, 349 - 358, 05.01.2026

Öz

Kaynakça

  • 1. Hausman, DM. What Is Cancer? Perspectives in Biology and Medicine 2019:62(4):778–784.
  • 2. Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA. et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747–752.
  • 3. Rossi L, Mazzara C, Pagani O. Diagnosis and Treatment of Breast Cancer in Young Women. Current Treatment Options in Oncology. 2019;20(12):86.
  • 4. Bitar SA., El-Sabban M, Doughan S, Abou-Kheir, W. Molecular mechanisms targeting drug-resistance and metastasis in colorectal cancer: Updates and beyond. World Journal of Gastroenterology. 2023;29(9):1395–1426.
  • 5. Zhu G, Pei L, Xia H, Tang Q, Bi F. Role of oncogenic KRAS in the prognosis, diagnosis and treatment of colorectal cancer. Molecular Cancer. 2021;20(1):143.
  • 6. Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, et al. Global Cancer Observatory: Cancer Today. Lyon: International Agency for Research on Cancer. 2020; (https://gco.iarc.fr/ today (Accessed February 2021).
  • 7. de Martel C, Georges D, Bray F, Ferlay J, Clifford GM. Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis. Lancet Glob Health. 2020;8(2):e180–e190.
  • 8. Biswas P, Ghorai M, Mishra T, Gopalakrishnan AV, Roy D, Mane AB, et al. Piper longum L.: A comprehensive review on traditional uses, phytochemistry, pharmacology, and health‐promoting activities. Phytotherapy Research. 2022;36(12):4425–4476.
  • 9. Zaveri M, Khandhar A, Patel S, Patel A. Chemistry and pharmacology of Piper longum L. International journal of pharmaceutical sciences review and research. 2010;5(1):67–76.
  • 10. Chanchal C, Thongam B, Handique PJ. Morphological diversity and characterization of some of the wild Piper species of North East India. Genetic Resources and Crop Evolution. 2015;62:303–313.
  • 11. Yadav V, Krishnan A, Vohora DA. systematic review on Piper longum L.: Bridging traditional knowledge and pharmacological evidence for future translational research. Journal of Ethnopharmacology. 2020;247, 112255.
  • 12. Kumar S, Kamboj J, Suman, Sunil Sharma S. Overview for Various Aspects of the Health Benefits of Piper Longum Linn. Fruit. J Acupunct Meridian Stud. 2011;4(2):134−140.
  • 13. Wang Y, Wang J. W., X. Xiao, Y. Shan, B. Xue, G. Jiang, Q. He, J. Chen, H. G. Xu, R. X. Zhao, K. D. Werle, R. Cui, J. Liang, Y. L. Li, Z. X. Xu. (2013). Piperlongumine induces autophagy by targeting p38 signaling. Cell Death Dis. 2013;4(2013):e824.
  • 14. Patel K, Chowdhury N, Doddapaneni R, Boakye C, Godugu C, Singh M. Piperlongumine for Enhancing Oral Bioavailability and Cytotoxicity of Docetaxel in Triple-Negative Breast Cancer. Journal of pharmaceutical sciences. 2015;104(12):4417–4426.
  • 15. Basak D, Punganuru SR., Srivenugopal KS. Piperlongumine exerts cytotoxic effects against cancer cells with mutant p53 proteins at least in part by restoring the biological functions of the tumor suppressor. Int. J. Oncol. 2016;48(2016):1426–1436.
  • 16. Park JA, Na HH, Jin HO, Kim KC. Increased Expression of FosB through Reactive Oxygen Species Accumulation Functions as Pro-Apoptotic Protein in Piperlongumine Treated MCF7 Breast Cancer Cells. Mol Cells. 2019; 31;42(12):884–892.
  • 17. Kumar S, Agnihotri N. Piperlongumine targets NF-κB and its downstream signaling pathways to suppress tumor growth and metastatic potential in experimental colon cancer. Mol Cell Biochem. 2021;476:1765–1781.
  • 18. Awasthee N, Shekher, A, Rai, Verma SS, Mishra S, Dhasmana A, Gupta SC. Piperlongumine, a piper alkaloid, enhances the efficacy of doxorubicin in breast cancer: Involvement of glucose import, ROS, NF-κB and lncRNAs. Apoptosis: An International Journal on Programmed Cell Death. 2022;27(3-4):261–282.
  • 19. Longley DB, Harkin DP, Johnston PG. 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003;3(5):330–8.
  • 20. Yildiz B, Demirel R, Havadar HB, Yildiz G, Öziç C, Kamiloğlu NN, et al. Blocking SIG1R Along with Low Cadmium Exposure Display Anti-cancer Qualities in Both MCF7 and MDA-MB-231 Cells. Biological Trace Element Research. 2023;202:3588–3600.
  • 21. Ribble D, Goldstein NB, Norris DA, Shellman YG. A simple technique for quantifying apoptosis in 96-well plates. BMC Biotechnol. 2005;5:12.
  • 22. Ozden O, Park SH, Wagner BA, Yong Song H, Zhu Y, Vassilopoulos A, et al. SIRT3 deacetylates and increases pyruvate dehydrogenase activity in cancer cells. Free Radical Biology and Medicine. 2014;76:163–172.
  • 23. Sharma D, Kapri A, Kumar S, Shiri T. Review on Anti-tumor activity, Immunomodulatory and neuromodulatory properties of Piper longum Linn. Journal of Ayurvedic and Herbal Medicine. 2022;8(1):55–60.
  • 24. Sinha A, Patel AS, Kamal P, Patel S, Srivastava A, Kumar S, Tiwari DM. Therapeutic Potential of Piper longum: A Review of Piperine and Piperlongumine in Human Health. Journal of Neonatal Surgery,. 2025;14(19).
  • 25. Fujihashi Y, Jo Kim M, Maneenet J, Awale S. (2023). Piper longum Constituents Induce PANC-1 Human Pancreatic Cancer Cell Death under Nutrition Starvation. Chemistry & Biodiversity. 2023;20(9):e202300280.
  • 26. Tripathi SK, Biswal BK. Piperlongumine, a potent anticancer phytotherapeutic: Perspectives on contemporary status and future possibilities as an anticancer agent. Pharmacological Research. 2020;156:104772.
  • 27. Turrini E, Sestili P, Fimognari C. Overview of the Anticancer Potential of the “King of Spices” Piper nigrum and Its Main Constituent Piperine. Toxins. 2020;12(12):747.
  • 28. Wan Q, Xu J, Zhu C, Liu X, Tu Y, Lei J, Yu J. Alkaloids from Piper longum Exhibit Anti-inflammatory Activity and Synergistic Effects with Chemotherapeutic Agents against Cervical Cancer Cells. J Agric Food Chem. 2023;Jul 12;71(27):10349–10360.
  • 29. Jeon SJ, Choi EY, Han EJ, Lee SW, Moon JM, Jung SH, et al. Piperlongumine induces apoptosis via the MAPK pathway and ERK-mediated autophagy in human melanoma cells. International Journal of Molecular Medicine. 2023;52(6):1–11
  • 30. Ovadje P, Ma D, Tremblay P, Roma A, Steckle M, Guerrero JA, et al. Evaluation of the Efficacy & Biochemical Mechanism of Cell Death Induction by Piper longum Extract Selectively in InVitro and In-Vivo Models of Human Cancer Cells. PLos One. 2014;9(11):e113250.
  • 31. Wang H, Wang Y, Gao H, Wang B, Dou L, Li Y. Piperlongumine induces apoptosis and autophagy in leukemic cells through targeting the PI3K/Akt/mTOR and p38 signaling pathways. Oncology Letters. 2018;15(2):1423–1428.
  • 32. Kung FP, Lim YP, Chao WY, Zhang YS, Yu HI, Tai TS, et al. Piperlongumine, a Potent Anticancer Phytotherapeutic, Induces Cell Cycle Arrest and Apoptosis In Vitro and In Vivo through the ROS/Akt Pathway in Human Thyroid Cancer Cells. Cancers. 2021;13(17):4266.
  • 33. Brix N, Samaga D, Hennel R, Gehr K, Zitzelsberger H, Lauber K. The clonogenic assay: Robustness of plating efficiencybased analysis is strongly compromised by cellular cooperation. Radiation Oncology. 2020;15(1):248.
  • 34. Franken NAP, Rodermond HM, Stap J, Haveman J, van Bree C. Clonogenic assay of cells in vitro. Nature Protocols. 2006;1(5):2315–2319.
  • 35. Lau TS, Chan LKY, Wong ECH, Hui CWC, Sneddon K, Cheung TH, et al. A loop of cancer-stroma-cancer interaction promotes peritoneal metastasis of ovarian cancer via TNFαTGFα-EGFR. Oncogene. 2017;36(25):3576–3587.
  • 36. Yildiz B, Demirel R, Staudacher JJ, Beseren H, Yildiz G, Akpinar AE, et al. SIRT2 deacetylates and decreases the expression of FOXM1 in colon cancer. Journal of Biochemical and Molecular Toxicology. 2024;38(11):e70018.
  • 37. Finley LWS, Carracedo A, Lee J, Souza A, Egia A, Zhang J, et al. SIRT3 Opposes Reprogramming of Cancer Cell Metabolism through HIF1α Destabilization. Cancer Cell. 2011;19(3):416–428.
  • 38. Haigis MC, Deng CX, Finley LWS, Kim HS, Gius D. SIRT3 is a mitochondrial tumor suppressor: A scientific tale that connects aberrant cellular ROS, the Warburg effect, and carcinogenesis. Cancer Research. 2012;72(10):2468–2472
Toplam 38 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Klinik Tıp Bilimleri (Diğer)
Bölüm Araştırma Makalesi
Yazarlar

Sevcan Mercan

Cansu Beytur

Ramazan Demirel

Özkan Özden

Gönderilme Tarihi 31 Mayıs 2025
Kabul Tarihi 11 Ağustos 2025
Yayımlanma Tarihi 5 Ocak 2026
Yayımlandığı Sayı Yıl 2025 Cilt: 15 Sayı: 3

Kaynak Göster

APA Mercan, S., Beytur, C., Demirel, R., Özden, Ö. (2026). Anticarcinogenic Properties of Piper longum Linn Extract in Combination with 5-Fluorouracil Chemotherapeutic Drug in Colon (DLD1) and Breast (MDA-MB-231) Cancer Cell Lines: Piper longum L. Exhibits Anticarcinogenic Effects in Both Cancer Cell Lines. Kafkas Journal of Medical Sciences, 15(3), 349-358.
AMA Mercan S, Beytur C, Demirel R, Özden Ö. Anticarcinogenic Properties of Piper longum Linn Extract in Combination with 5-Fluorouracil Chemotherapeutic Drug in Colon (DLD1) and Breast (MDA-MB-231) Cancer Cell Lines: Piper longum L. Exhibits Anticarcinogenic Effects in Both Cancer Cell Lines. KAFKAS TIP BİL DERG. Ocak 2026;15(3):349-358.
Chicago Mercan, Sevcan, Cansu Beytur, Ramazan Demirel, ve Özkan Özden. “Anticarcinogenic Properties of Piper longum Linn Extract in Combination with 5-Fluorouracil Chemotherapeutic Drug in Colon (DLD1) and Breast (MDA-MB-231) Cancer Cell Lines: Piper longum L. Exhibits Anticarcinogenic Effects in Both Cancer Cell Lines”. Kafkas Journal of Medical Sciences 15, sy. 3 (Ocak 2026): 349-58.
EndNote Mercan S, Beytur C, Demirel R, Özden Ö (01 Ocak 2026) Anticarcinogenic Properties of Piper longum Linn Extract in Combination with 5-Fluorouracil Chemotherapeutic Drug in Colon (DLD1) and Breast (MDA-MB-231) Cancer Cell Lines: Piper longum L. Exhibits Anticarcinogenic Effects in Both Cancer Cell Lines. Kafkas Journal of Medical Sciences 15 3 349–358.
IEEE S. Mercan, C. Beytur, R. Demirel, ve Ö. Özden, “Anticarcinogenic Properties of Piper longum Linn Extract in Combination with 5-Fluorouracil Chemotherapeutic Drug in Colon (DLD1) and Breast (MDA-MB-231) Cancer Cell Lines: Piper longum L. Exhibits Anticarcinogenic Effects in Both Cancer Cell Lines”, KAFKAS TIP BİL DERG, c. 15, sy. 3, ss. 349–358, 2026.
ISNAD Mercan, Sevcan vd. “Anticarcinogenic Properties of Piper longum Linn Extract in Combination with 5-Fluorouracil Chemotherapeutic Drug in Colon (DLD1) and Breast (MDA-MB-231) Cancer Cell Lines: Piper longum L. Exhibits Anticarcinogenic Effects in Both Cancer Cell Lines”. Kafkas Journal of Medical Sciences 15/3 (Ocak2026), 349-358.
JAMA Mercan S, Beytur C, Demirel R, Özden Ö. Anticarcinogenic Properties of Piper longum Linn Extract in Combination with 5-Fluorouracil Chemotherapeutic Drug in Colon (DLD1) and Breast (MDA-MB-231) Cancer Cell Lines: Piper longum L. Exhibits Anticarcinogenic Effects in Both Cancer Cell Lines. KAFKAS TIP BİL DERG. 2026;15:349–358.
MLA Mercan, Sevcan vd. “Anticarcinogenic Properties of Piper longum Linn Extract in Combination with 5-Fluorouracil Chemotherapeutic Drug in Colon (DLD1) and Breast (MDA-MB-231) Cancer Cell Lines: Piper longum L. Exhibits Anticarcinogenic Effects in Both Cancer Cell Lines”. Kafkas Journal of Medical Sciences, c. 15, sy. 3, 2026, ss. 349-58.
Vancouver Mercan S, Beytur C, Demirel R, Özden Ö. Anticarcinogenic Properties of Piper longum Linn Extract in Combination with 5-Fluorouracil Chemotherapeutic Drug in Colon (DLD1) and Breast (MDA-MB-231) Cancer Cell Lines: Piper longum L. Exhibits Anticarcinogenic Effects in Both Cancer Cell Lines. KAFKAS TIP BİL DERG. 2026;15(3):349-58.