The Chemosensitizing Effect of Portulaca oleracea Methanol Extract on Human Colorectal and Lung Cancer Cells Against Irinotecan
Abstract
Cancer is a major health problem and it has been causing great damage in recent years worldwide. Serious side effects of chemotherapeutics used in cancer treatment make natural products valuable. Combined use of chemotherapy drugs and herbal products is an important approach in reducing side effects and revealing a more effective treatment. In this study, the effects of methanolic extract from Portulaca oleracea (POM) alone and in combination with Irinotecan were investigated against human colorectal carcinoma cell line HCT-116 and human lung adenocarcinoma cell line A549. The antiproliferative/anti-colony formation effects were determined using WST-1 assay and clonogenic assay. Cell death detection Elisa assay was employed to exhibite the triggered apoptosis, and quantitative real time polimerase chain reaction (qRT-PCR) was performed to evaluate the mRNA expression of mTOR, Akt and PTEN genes, which are significant modulators of apoptotic and survival pathways. It was determined that 72 h treatment with increasing concentrations of POM (0-1000 mg mL-1) decreased the viability of HCT116 and A549 cells in a dose-dependent manner. Also, POM and Irinotecan exhibited synergistic effects in both cell lines. The combination of POM and Irinotecan suppressed the colony forming capacity of HCT116 and A549 cells by 84% and 79%, respectively. POM also altered mTOR, Akt and PTEN gene expressions in HCT-116 and A549 carcinoma cells, both alone and in combination with Irinotecan. This study shows that the phytotherapeutic effect of P. oleracea needs to be studied more intensively.
Thanks
The author would like to thank Mr. Yakup Yapar from Faculty of Arts and Sciences, Department of Biology, Bingol University for his kindly efforts in the identification of the plant samples and in the creation of herbarium records.
References
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- Aizpurua‐Olaizola O, Ormazabal M, Vallejo A, Olivares M, Navarro P, Etxebarria N, Usobiaga A 2015. Optimization of supercritical fluid consecutive extractions of fatty acids and polyphenols from Vitis vinifera grape wastes. Journal of food science 80(1): E101-E107.
- Al-Sheddi ES, Farshori NN, Al-Oqail MM, Musarrat J, Al-Khedhairy AA, Siddiqui MA 2015. Portulaca oleracea seed oil exerts cytotoxic effects on human liver cancer (HepG2) and human lung cancer (A-549) cell lines. Asian Pac J Cancer Prev 16(8): 3383-7.
- Borah P, Banik BK 2020. Medicinal plants and their compounds with anticancer properties. In Green Approaches in Medicinal Chemistry for Sustainable Drug Design 759-776.
- Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A 2018. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians 68(6): 394-424.
- Carneiro BA, El-Deiry WS 2020. Targeting apoptosis in cancer therapy. Nature Reviews Clinical Oncology 1-23.
- Chou TC, Talalay P 1984. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Advances in Enzyme Regulation 22: 27–55.
- El-burai H, Alzaharna M, Isleem R, El-Hindi M, Sharif F 2020. Anticancer activity of Rosemary (Rosmarinus officinalis L.) and Oats (Avena sativa L.) Extracts, and their antitumor enhancement of 5-Fluorouracil on Colon Cancer Caco-2 Cell Line. International Journal of Herbal Medicine 8(3): 138-146.
- Erdogan MK, Agca CA, Askın H 2020b. Achillea biebersteinii extracts suppress angiogenesis and enhance sensitivity to 5-fluorouracil of human colon cancer cells via the PTEN/AKT/mTOR pathway in vitro. Asian Pacific Journal of Tropical Biomedicine 10(11): 505-515.
- Erdogan MK, Agca CA, Askin H 2019. Enhanced antiproliferative and apoptotic effects of 5-fluorouracil by combined with Pistacia eurycarpa Extracts on human colorectal cancer cells. Biological Diversity and Conservation 12(1): 27-38.
- Erdogan MK, Gecibesler İH, Behcet L 2020a. Chemical constituents, antioxidant, antiproliferative and apoptotic effects of a new endemic Boraginaceae species: Paracaryum bingoelianum. Results in Chemistry 2: 100032.
- Ferreira CG, Epping M, Kruyt FA, Giaccone G 2002. Apoptosis: target of cancer therapy. Clinical Cancer Research 8(7): 2024-2034.
- Franken NA, Rodermond HM, Stap J, Haveman J, Van Bree C 2006. Clonogenic assay of cells in vitro. Nature protocols 1(5): 2315-2319.
- Gecibesler IH, Erdogan M 2019. A new nutraceutical resource from a rare native plant growing in Turkey and for its spectro-chemical and biological insights: Endemic Diplotaenia bingolensis (Apiaceae). Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 223: 117358.
- Huang H, Wang X, Zhang X, Zhang G, Jinbo M, Wang H, Jiang W 2020. Ganciclovir reduces irinotecan-induced intestinal toxicity by inhibiting NLRP3 activation. Cancer Chemotherapy and Pharmacology 85(1): 195-204.
- Jayathilake AG, Kadife E, Luwor RB, Nurgali K, Su XQ 2019. Krill oil extract suppresses the proliferation of colorectal cancer cells through activation of caspase 3/9. Nutrition & Metabolism 16(1): 1-15.
- Li J, Wang R, Kong Y, Broman MM, Carlock C, Chen L, Liu X 2017. Targeting Plk1 to Enhance Efficacy of Olaparib in Castration-Resistant Prostate Cancer. Molecular Cancer Therapeutics 16(3): 469–479.
- Lim YY, Quah EP 2007. Antioxidant properties of different cultivars of Portulaca oleracea. Food chemistry 103(3): 734-740.
- Livak KJ, Schmittgen TD 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods 25(4): 402-408.
- Luzhetskyy A, Pelzer S, Bechthold A 2007. The future of natural products as a source of new antibiotics. Current opinion in investigational drugs (London, England: 2000) 8(8): 608-613.
- Majolo F, Delwing LKDOB, Marmitt DJ, Bustamante-Filho IC, Goettert MI 2019. Medicinal plants and bioactive natural compounds for cancer treatment: Important advances for drug discovery. Phytochemistry Letters 31: 196-207.
- Mali PY 2015. Assessment of cytotoxicity of Portulaca oleracea Linn. against human colon adenocarcinoma and vero cell line. Ayu 36(4): 432.
- Nemzer B, Al-Taher F, Abshiru N 2020. Phytochemical composition and nutritional value of different plant parts in two cultivated and wild purslane (Portulaca oleracea L.) genotypes. Food Chemistry 126621.
- Newman DJ, Cragg GM 2016. Natural products as sources of new drugs from 1981 to 2014. Journal of natural products 79(3): 629-661.
- Ocana A, Vera-Badillo F, Al-Mubarak M, Templeton AJ, Corrales-Sanchez V, Diez-Gonzalez L, Amir E 2014. Activation of the PI3K/mTOR/AKT pathway and survival in solid tumors: systematic review and meta-analysis. PloS one 9(4): e95219.
- Ojima I 2008. Modern natural products chemistry and drug discovery. Journal of medicinal chemistry 51(9): 2587-2588.
- Rahimi VB, Mousavi SH, Haghighi S, Soheili-Far S, Askari VR 2019. Cytotoxicity and apoptogenic properties of the standardized extract of Portulaca oleracea on glioblastoma multiforme cancer cell line (U-87): a mechanistic study. EXCLI journal 18: 165.
- Rajesh E, Sankari LS, Malathi L, Krupaa JR 2015. Naturally occurring products in cancer therapy. Journal of pharmacy & bioallied sciences 7(Suppl 1): S181.
- Xiang L, Xing D, Wang W, Wang R, Ding Y, Du L 2005. Alkaloids from Portulaca oleracea L. Phytochemistry 66(21): 2595-2601.
- Younes M, Ammoury C, Haykal T, Nasr L, Sarkis R, Rizk S 2020. The selective anti-proliferative and pro-apoptotic effect of A. cherimola on MDA-MB-231 breast cancer cell line. BMC Complementary Medicine and Therapies 20(1): 1-10.
- Zheng GY, Qu LP, Yue XQ, Gu W, Zhang H, Xin HL 2014. Portulacerebroside A induces apoptosis via activation of the mitochondrial death pathway in human liver cancer HCCLM3 cells. Phytochemistry Letters 7: 77-84.
- Zhou YX, Xin HL, Rahman K, Wang SJ, Peng C, Zhang H 2015. Portulaca oleracea L.: a review of phytochemistry and pharmacological effects. BioMed research international 2015.
Portulaca oleracea Metanol Ekstraktının İnsan Kolorektal ve Akciğer Kanseri Hücrelerini Irinotekana Karşı Kemohassaslaştırıcı Etkisi
Abstract
Kanser büyük bir sağlık sorunudur ve son yıllarda dünya çapında büyük zararlara neden olmaktadır. Kanser tedavisinde kullanılan kemoterapötiklerin ciddi yan etkileri, doğal ürünleri değerli kılmaktadır. Kemoterapi ilaçları ile bitkisel ürünlerin birlikte kullanılması, yan etkilerin azaltılması ve daha etkili bir tedavinin ortaya çıkarılmasında önemli bir yaklaşımdır. Bu çalışmada, tek başına ve Irinotekan ile kombinasyon halinde Portulaca oleracea'dan metanol ekstraktının (POM) etkileri, insan kolorektal karsinoma hücre hattı HCT-116 ve insan akciğer adenokarsinom hücre hattı A549'a karşı araştırılmıştır. Antiproliferatif / anti-koloni oluşumu etkileri, WST-1 deneyi ve kloni oluşumu deneyi ile belirlendi. Hücre ölümü tespiti Elisa testi tetiklenen apoptozu göstermek için kullanıldı, ve apoptotik ve hayatta kalma yollarının önemli modülatörleri olan mTOR, Akt ve PTEN genlerinin mRNA ekspresyonunu değerlendirmek için kantitatif gerçek zamanlı polimeraz zincir reaksiyonu (qRT-PCR) yapıldı. Artan POM konsantrasyonları (0-1000 mg mL-1) ile 72 saatlik tedavinin doza bağlı olarak HCT116 ve A549 hücrelerinin canlılığını azalttığı belirlendi. Ayrıca, POM ve Irinotekan, her iki hücre hattında da sinerjik etkiler sergiledi. POM ve Irinotekan kombinasyonu, HCT116 ve A549 hücrelerinin koloni oluşturma kapasitesini sırasıyla % 84 ve % 79 oranında baskıladı. POM ayrıca HCT-116 ve A549 karsinom hücrelerinde mTOR, Akt ve PTEN gen ekspresyonlarını hem tek başına hem de Irinotekan ile kombinasyon halinde değiştirdi. Bu çalışma, P. oleracea'nın fitoterapötik etkisinin daha yoğun olarak araştırılması gerektiğini göstermektedir.
References
- Afolayan FI, Sulaiman KA, Okunade WT 2020. Ethnobotanical survey of plants used in cancer therapy in Iwo and Ibadan, South-Western of Nigeria. Journal of Pharmacy & Pharmacognosy Research 8(5): 346-367.
- Aizpurua‐Olaizola O, Ormazabal M, Vallejo A, Olivares M, Navarro P, Etxebarria N, Usobiaga A 2015. Optimization of supercritical fluid consecutive extractions of fatty acids and polyphenols from Vitis vinifera grape wastes. Journal of food science 80(1): E101-E107.
- Al-Sheddi ES, Farshori NN, Al-Oqail MM, Musarrat J, Al-Khedhairy AA, Siddiqui MA 2015. Portulaca oleracea seed oil exerts cytotoxic effects on human liver cancer (HepG2) and human lung cancer (A-549) cell lines. Asian Pac J Cancer Prev 16(8): 3383-7.
- Borah P, Banik BK 2020. Medicinal plants and their compounds with anticancer properties. In Green Approaches in Medicinal Chemistry for Sustainable Drug Design 759-776.
- Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A 2018. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians 68(6): 394-424.
- Carneiro BA, El-Deiry WS 2020. Targeting apoptosis in cancer therapy. Nature Reviews Clinical Oncology 1-23.
- Chou TC, Talalay P 1984. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Advances in Enzyme Regulation 22: 27–55.
- El-burai H, Alzaharna M, Isleem R, El-Hindi M, Sharif F 2020. Anticancer activity of Rosemary (Rosmarinus officinalis L.) and Oats (Avena sativa L.) Extracts, and their antitumor enhancement of 5-Fluorouracil on Colon Cancer Caco-2 Cell Line. International Journal of Herbal Medicine 8(3): 138-146.
- Erdogan MK, Agca CA, Askın H 2020b. Achillea biebersteinii extracts suppress angiogenesis and enhance sensitivity to 5-fluorouracil of human colon cancer cells via the PTEN/AKT/mTOR pathway in vitro. Asian Pacific Journal of Tropical Biomedicine 10(11): 505-515.
- Erdogan MK, Agca CA, Askin H 2019. Enhanced antiproliferative and apoptotic effects of 5-fluorouracil by combined with Pistacia eurycarpa Extracts on human colorectal cancer cells. Biological Diversity and Conservation 12(1): 27-38.
- Erdogan MK, Gecibesler İH, Behcet L 2020a. Chemical constituents, antioxidant, antiproliferative and apoptotic effects of a new endemic Boraginaceae species: Paracaryum bingoelianum. Results in Chemistry 2: 100032.
- Ferreira CG, Epping M, Kruyt FA, Giaccone G 2002. Apoptosis: target of cancer therapy. Clinical Cancer Research 8(7): 2024-2034.
- Franken NA, Rodermond HM, Stap J, Haveman J, Van Bree C 2006. Clonogenic assay of cells in vitro. Nature protocols 1(5): 2315-2319.
- Gecibesler IH, Erdogan M 2019. A new nutraceutical resource from a rare native plant growing in Turkey and for its spectro-chemical and biological insights: Endemic Diplotaenia bingolensis (Apiaceae). Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 223: 117358.
- Huang H, Wang X, Zhang X, Zhang G, Jinbo M, Wang H, Jiang W 2020. Ganciclovir reduces irinotecan-induced intestinal toxicity by inhibiting NLRP3 activation. Cancer Chemotherapy and Pharmacology 85(1): 195-204.
- Jayathilake AG, Kadife E, Luwor RB, Nurgali K, Su XQ 2019. Krill oil extract suppresses the proliferation of colorectal cancer cells through activation of caspase 3/9. Nutrition & Metabolism 16(1): 1-15.
- Li J, Wang R, Kong Y, Broman MM, Carlock C, Chen L, Liu X 2017. Targeting Plk1 to Enhance Efficacy of Olaparib in Castration-Resistant Prostate Cancer. Molecular Cancer Therapeutics 16(3): 469–479.
- Lim YY, Quah EP 2007. Antioxidant properties of different cultivars of Portulaca oleracea. Food chemistry 103(3): 734-740.
- Livak KJ, Schmittgen TD 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods 25(4): 402-408.
- Luzhetskyy A, Pelzer S, Bechthold A 2007. The future of natural products as a source of new antibiotics. Current opinion in investigational drugs (London, England: 2000) 8(8): 608-613.
- Majolo F, Delwing LKDOB, Marmitt DJ, Bustamante-Filho IC, Goettert MI 2019. Medicinal plants and bioactive natural compounds for cancer treatment: Important advances for drug discovery. Phytochemistry Letters 31: 196-207.
- Mali PY 2015. Assessment of cytotoxicity of Portulaca oleracea Linn. against human colon adenocarcinoma and vero cell line. Ayu 36(4): 432.
- Nemzer B, Al-Taher F, Abshiru N 2020. Phytochemical composition and nutritional value of different plant parts in two cultivated and wild purslane (Portulaca oleracea L.) genotypes. Food Chemistry 126621.
- Newman DJ, Cragg GM 2016. Natural products as sources of new drugs from 1981 to 2014. Journal of natural products 79(3): 629-661.
- Ocana A, Vera-Badillo F, Al-Mubarak M, Templeton AJ, Corrales-Sanchez V, Diez-Gonzalez L, Amir E 2014. Activation of the PI3K/mTOR/AKT pathway and survival in solid tumors: systematic review and meta-analysis. PloS one 9(4): e95219.
- Ojima I 2008. Modern natural products chemistry and drug discovery. Journal of medicinal chemistry 51(9): 2587-2588.
- Rahimi VB, Mousavi SH, Haghighi S, Soheili-Far S, Askari VR 2019. Cytotoxicity and apoptogenic properties of the standardized extract of Portulaca oleracea on glioblastoma multiforme cancer cell line (U-87): a mechanistic study. EXCLI journal 18: 165.
- Rajesh E, Sankari LS, Malathi L, Krupaa JR 2015. Naturally occurring products in cancer therapy. Journal of pharmacy & bioallied sciences 7(Suppl 1): S181.
- Xiang L, Xing D, Wang W, Wang R, Ding Y, Du L 2005. Alkaloids from Portulaca oleracea L. Phytochemistry 66(21): 2595-2601.
- Younes M, Ammoury C, Haykal T, Nasr L, Sarkis R, Rizk S 2020. The selective anti-proliferative and pro-apoptotic effect of A. cherimola on MDA-MB-231 breast cancer cell line. BMC Complementary Medicine and Therapies 20(1): 1-10.
- Zheng GY, Qu LP, Yue XQ, Gu W, Zhang H, Xin HL 2014. Portulacerebroside A induces apoptosis via activation of the mitochondrial death pathway in human liver cancer HCCLM3 cells. Phytochemistry Letters 7: 77-84.
- Zhou YX, Xin HL, Rahman K, Wang SJ, Peng C, Zhang H 2015. Portulaca oleracea L.: a review of phytochemistry and pharmacological effects. BioMed research international 2015.
Details
| Primary Language | English |
|---|---|
| Subjects | Structural Biology |
| Journal Section | RESEARCH ARTICLE |
| Authors | |
| Publication Date | December 31, 2021 |
| Submission Date | January 6, 2021 |
| Acceptance Date | April 1, 2021 |
| Published in Issue | Year 2021Volume: 24 Issue: 6 |
Cited By
In vitro anticancer, antioxidant and enzyme inhibitory potentials of endemic Cephalaria elazigensis var. purpurea with in silico studies
Journal of Biomolecular Structure and Dynamics
https://doi.org/10.1080/07391102.2022.2163700
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