Cytotoxic Activity of Combining Molecular Iodine and Dihydroartemisinin with Methanol Extracts of Carica papaya Linn and Vernonia amygdalina Delile Leaves against MCF-7 and MDA-MB-231 Breast Cancer Cell Lines doi.org/10.26538/tjnpr/v5i3.12

Main Article Content

Jadwiga Nowak
Charles Wambebe
Jackson Mukonzo
Esther Katuura

Abstract

Carica papaya Linn (CP), Vernonia amygdalina Delile (VA), dihydroartemisinin (DHA), molecular iodine (I2) were reported to have antiproliferative and cytotoxic activities on breast cancer, but their anticancer effect once combined had not been explored. This study assessed the cytotoxic effect of combining I2, DHA, methanolic extracts of CP, VA leaves against MCF-7 and MDA-MB-231 breast cancer cell lines. Cytotoxic activity and cell viability of the plant extracts and combinations were determined using trypan blue assay with peripheral blood mononuclear cells(PBMCs) and doxorubicin (DOX) as negative and positive controls respectively. The study used SigmaPlot software to obtain IC50 values and drug interactions were determined using the isobologram and combination index (CI)(Chou-Talalay method).The combination of CP + VA revealed the strongest cytotoxic activity amongst tested combinations and individual extracts with CI < 1 and IC50 = 18.6 ± 2.5 on MCF-7. A combination of CP + VA + DHA with CI >1 was included in the study based on its possible multi-target mechanism of action. The cytotoxic effects of CP + VA, CP + VA + DHA were significantly lower when tested on PBMCs in comparison to activity against breast cancer cells. DOX showed higher cytotoxic activity on PBMCs when compared with the tested combinations. This study suggested CP + VA to be the most efficacious combination with strong antiproliferative effect on MCF-7 and lower toxicity to human PBMCs when compared to DOX. Each of the combination’s components was found to be less cytotoxic against chosen cell lines. 

Downloads

Download data is not yet available.

Article Details

How to Cite
Nowak, J., Wambebe, C., Mukonzo, J., & Katuura, E. (2021). Cytotoxic Activity of Combining Molecular Iodine and Dihydroartemisinin with Methanol Extracts of Carica papaya Linn and Vernonia amygdalina Delile Leaves against MCF-7 and MDA-MB-231 Breast Cancer Cell Lines: doi.org/10.26538/tjnpr/v5i3.12. Tropical Journal of Natural Product Research (TJNPR), 5(3), 485-493. https://tjnpr.org/index.php/home/article/view/730
Section
Articles

How to Cite

Nowak, J., Wambebe, C., Mukonzo, J., & Katuura, E. (2021). Cytotoxic Activity of Combining Molecular Iodine and Dihydroartemisinin with Methanol Extracts of Carica papaya Linn and Vernonia amygdalina Delile Leaves against MCF-7 and MDA-MB-231 Breast Cancer Cell Lines: doi.org/10.26538/tjnpr/v5i3.12. Tropical Journal of Natural Product Research (TJNPR), 5(3), 485-493. https://tjnpr.org/index.php/home/article/view/730

References

Akram M, Iqbal M, Daniyal M, Khan AU. Awareness and current knowledge of breast cancer. Bio res. 2017; 50(1):33.

Apuri S. Neoadjuvant and Adjuvant Therapies for Breast Cancer. Southern Med J. 2017; 110(10):638-642.

Lukong KE, Ogunbolude Y, Kamdem JP. Breast cancer in Africa: prevalence, treatment options, herbal medicines, and socioeconomic determinants. Breast Cancer Res and Treat. 2017; 166(2):351-365.

Pezzani R, Salehi B, Vitalini S, Iriti M, Zuñiga FA, SharifiRad J, Martorell M, Martins N. Synergistic effects of plant derivatives and conventional chemotherapeutic agents: An update on the cancer perspective. Medicina. 2019;55(4):110.

Boyd MR. The NCI in vitro anticancer drug discovery screen. In Anticancer drug development guide 1997. 23-42 p.

Likhitwitayawuid K, Angerhofer CK, Cordell GA, Pezzuto JM, Ruangrungsi N. Cytotoxic and antimalarial bisbenzylisoquinolme alkaloids from Stephania erecta. J Nat Prod. 1993; 56(1):30-38.

Mensah ML, Komlaga G, Forkuo AD, Firempong C, Anning AK, Dickson RA. Toxicity and safety implications of herbal medicines used in Africa. Herb Med. IntechOpen. 2019. 63-86 p.

Chou TC. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer res. 2010; 70(2):440-446.

Pinnamaneni R. Nutritional and medicinal value of papaya (Carica papaya Linn.). World J Pharm and Pharmaceut Sci. 2017; 6(8):2559-2578.

Saha S and Giri TK. Breaking the Barrier of Cancer through Papaya Extract and their Formulation. Anti-Cancer Agents in Med Chem (Formerly Current Med Chem-Anti-Cancer Agents). 2019; 19(13):1577-1587.

Rahmani AH and Aldebasi YH. Potential role of carica papaya and their active constituents in the prevention and treatment of diseases. Int J Pharm Pharm Sci. 2016; 8(1):11-15.

Kaur D, Kaur N, Chopra A. A comprehensive review on phytochemistry and pharmacological activities of Vernonia amygdalina. J Pharmacogn and Phytochem. 2019;8(3):2629-2636.

Wong FC, Woo CC, Hsu A, Tan BK. The anti-cancer activities of Vernonia amygdalina extract in human breast cancer cell lines are mediated through caspase-dependent and p53-independent pathways. PLoS One. 2013;8(10):e78021.

Singh NP and Panwar VK. Case report of a pituitary macroadenoma treated with artemether. Integrative cancer therapies. 2006; 5(4):391-394.

Luo H, Vong CT, Chen H, Gao Y, Lyu P, Qiu L, Zhao M, Liu Q, Cheng Z, Zou J, Yao P. Naturally occurring anticancer compounds: shining from Chinese herbal medicine. Chinese med. 2019; 14(1):48.

Jiang C, Li S, Li Y, Bai Y. Anticancer effects of dihydroartemisinin on human esophageal cancer cells in vivo. Analy cell pathology. 2018; 2018:7.

Feng MX, Hong JX, Wang Q, Fan YY, Yuan CT, Lei XH, Zhu M, Qin A, Chen HX, Hong D. Dihydroartemisinin prevents breast cancer-induced osteolysis via inhibiting both breast cancer cells and osteoclasts. Sci reports. 2016; 6:19074.

Zhao J, Pan Y, Li X, Zhang X, Xue Y, Wang T, Zhao S, Hou Y. Dihydroartemisinin and curcumin synergistically induce apoptosis in SKOV3 cells via upregulation of MiR-124 targeting midkine. Cell Physiol and Biochem. 2017;43(2):589-601.

Kaczor T. Iodine and cancer: a summary of the evidence to date. Nat Med J. 2014; 6(6).

Kato N. Suppressive effect of iodine preparations on proliferation of DMBA-induced breast cancer in rat. J Jpn Soc Cancer Ther. 1994; 29:582.

Shrivastava A, Tiwari M, Sinha RA, Kumar A, Balapure AK, Bajpai VK, Sharma R, Mitra K, Tandon A, Godbole MM. Molecular iodine induces caspase-independent apoptosis in human breast carcinoma cells involving the mitochondria-mediated pathway. J Bio Chem. 2006; 281(28):19762-19771.

Stoddard II FR, Brooks AD, Eskin BA, Johannes GJ. Iodine alters gene expression in the MCF7 breast cancer cell line: evidence for an anti-estrogen effect of iodine. Inter J med sci. 2008; 5(4):189.

Li S, So TH, Tang G, Tan HY, Wang N, Ng BF, Chan CK, Yu EC, Feng Y. Chinese Herbal Medicine for Reducing Chemotherapy-Associated Side-Effects in Breast Cancer Patients: A Systematic Review and Meta-Analysis. Frontiers in Oncology. 2020; 10: 599073.

Shahid U. Herbal treatment strategies for breast cancer. OMICS group of ebooks. 2013.

Grady D. Uganda fights stigma and poverty to take on breast cancer. The New York Times. 2013; 10:15.

Kiwanuka F. Complementary and alternative medicine use: influence of patients’ satisfaction with medical treatment among breast cancer patients at Uganda Cancer Institute. Advances in Biosci and Clin Med. 2018; 6(1):24-29.

MoH. Annual health sector performance report. Kampala: Ministry of Health. 2011.

Rockwell S, Liu Y, Higgins SA. Alteration of the effects of cancer therapy agents on breast cancer cells by the herbal medicine black cohosh. Breast Cancer Res and Treat. 2005;90(3):233-239.

Holliday DL and Speirs V. Choosing the right cell line for breast cancer research. Breast cancer research. 2011;13(4):1-7.

Patil T, Patil S, Patil A, Patil S. Carica papaya leaf extracts–An Ethnomedicinal boon. Inter J Pharmacogn and Phytochem Res. 2014; 6(2):260-265.

Rockwell S, Liu Y, Higgins SA. Alteration of the effects of cancer therapy agents on breast cancer cells by the herbal medicine black cohosh. Breast cancer Res and treat. 2005;90(3):233-239.

Noor Atiqah AA, Maisarah AM, Asmah R. Comparison of antioxidant properties of tamarillo (Cyphomandra betacea), cherry tomato (Solanumly copersicum var. cerasiform) and tomato (Lyopersicon esulentum). Inter Food Res J. 2014;21(6):2355-2362.

Wong FC, Woo CC, Hsu A, Tan BK. The anti-cancer activities of Vernonia amygdalina extract in human breast cancer cell lines are mediated through caspase-dependent and p53-independent pathways. PLoS One. 2013;8(10):e78021.

Zhao J, Pan Y, Li X, Zhang X, Xue Y, Wang T, Zhao S, Hou Y. Dihydroartemisinin and curcumin synergistically induce apoptosis in SKOV3 cells via upregulation of MiR-124 targeting midkine. Cellular Physiol and Biochem. 2017;43(2):589-601.

Lai HC, Singh NP, Sasaki T. Development of artemisinin compounds for cancer treatment. Investigate new drugs. 2013; 31(1):230-246.

Borges CV, Minatel IO, Gomez-Gomez HA, Lima GP. Medicinal plants: Influence of environmental factors on the content of secondary metabolites. In Medicinal Plants and Environmental Challenges [Online]. 2017 [cited 13 Jan. 2021]. Available from: http://hdl.handle.net/11449/175954

American Cancer Society. Breast cancer facts & figures 2017–2018. American Cancer Society Inc.: Atlanta, 2017.

Yedjou CG and Tchounwou P. Mechanisms of Vernonia amygdalina-induced apoptosis of human breast adenocarcinoma (MCF-7) cells. Cancer Res. 2014; 74:127.

Efferth T and Koch E. Complex interactions between phytochemicals. The multi-target therapeutic concept of phytotherapy. Current drug targets. 2011; 12(1):122-132.

Lin NU, Vanderplas A, Hughes ME, Theriault RL, Edge SB, Wong Y, Blayney DW, Niland JC, Winer EP, Weeks JC. Clinicopathological features and sites of recurrence according to breast cancer subtype in the National Comprehensive Cancer Network (NCCN). J Clin Oncology.

; 27(15):543.

Van Vuuren S and Viljoen, A. Plant-based antimicrobial studies–methods and approaches to study the interaction between natural products. Planta medica. 2011; 77(11):1168-1182.

Wagner H and Ulrich-Merzenich G. Synergy research: approaching a new generation of phytopharmaceuticals. Phytomedicine. 2009; 16(2-3):97-110.

Pemovska T, Bigenzahn JW, Superti-Furga G. Recent advances in combinatorial drug screening and synergy scoring. Current opinion in pharmacol. 2018; 42:102-110.

Tang J, Wennerberg K, Aittokallio T. What is synergy? The Saariselkä agreement revisited. Frontiers in pharmacology. 2015; 6:181.

Berenbaum MC. What is synergy?. Pharmacol reviews. 1989; 41(2):93-141.

Rather MA, Bhat BA, Qurishi MA. Multicomponent phytotherapeutic approach gaining momentum: Is the “one drug to fit all” model breaking down?. Phytomedicine. 2013; 21(1):1-4.