تجزیهوتحلیل بیوانفورماتیک و بررسی بیان ژن PI3K/AKT در مواجهه با ماده موثره سینامون موجود در گیاه دارچین
محورهای موضوعی :
زیست شناسی سلولی تکوینی گیاهی و جانوری ، تکوین و تمایز ، زیست شناسی میکروارگانیسم
محدثه اسماعیل نژاد چماچایی
1
,
سمیه عطایی جلیسه
2
,
شادی محبوبی
3
1 - گروه زیست شناسی، واحد رشت، دانشگاه آزاد اسلامی، رشت، ایران
2 - گروه زیست شناسی، واحد رشت، دانشگاه آزاد اسلامی، رشت، ایران
3 - گروه زیست شناسی، واحد رشت، دانشگاه آزاد اسلامی، رشت، ایران
تاریخ دریافت : 1401/08/22
تاریخ پذیرش : 1401/10/11
تاریخ انتشار : 1402/09/01
کلید واژه:
In-vitro,
دارچین,
in-silico,
سینامون,
PI3K/AKT,
چکیده مقاله :
دارچین نوعی ادویه ی مقوی است که به خاطر تأثیراتش در سلامت بدن از دیرباز جایگاه ویژه ای در طب سنتی داشته است. امروزه نیز با کشف خواص درمانی گسترده ی آن در بسیاری از کشورها مورد استفاده قرار میگیرد. اجزای اصلی دارچین، از جمله سینامالدئید، می توانند در درمان سرطان سینه نقش داشته باشند. در این مطالعه به بررسی اثر آنتی اکسیدانی و خواص ضد سرطانی ماده موثره موجود در دارچین (سینامون) در سرطان پستان پرداختیم. دوز ماده موثره سینامون به روش تست MTT تعیین و بررسی شد. بررسی اثرات ماده موثره سینامون در مسیر سیگنالینگ PI3K/AKT ، با استفاده از روش داکینگ مولکولی و Real-time PCR انجام شد. نتایج بدین صورت بودند که مقدار دوز ماده موثره معادل با mg/ml093/0 بود و از بین چهار پروتئین مورد نظر ، ژن AKT به دلیل بیشترین و بهترین واکنش در سطح پروتئین انتخاب شد و بیان ژن AKT در حضور سینامون بسیار کم شد. با توجه به اثرات ، فعالیت وخواص آنتی اکسیدانی ماده موثره سینامون با در نظر گرفتن عوارض جانبی آنها در شرایط in vitro و in silico می توان از این ماده موثره گیاه، به عنوان یک مهار کننده مسیر سیگنالینگ PI3K/AKT و همچنین جلوگیری کننده از تومورهای بدخیم استفاده کرد.
چکیده انگلیسی:
Cinnamomum is a type of tonic spice that has had a special place in traditional medicine for a long time due to its effects on body health. Even today, with the discovery of its wide therapeutic properties, it is used in many countries. The main components of Cinnamomum, including cinnamaldehyde, can play a role in the treatment of breast cancer. In this study, we investigated the antioxidant effect and anticancer properties of the active ingredient in cinnamon in breast cancer. The dose of the active ingredient of cinnamon was determined and checked by the MTT test method. The effects of cinnamon active substance on PI3K/AKT signaling pathway were investigated using molecular docking and real-time PCR methods. The results were that the dose of the effective substance was equal to 0.093 mg/ml and among the four proteins, AKT gene was selected due to the highest and best reaction at the protein level and the expression of AKT gene was very low in the presence of cinnamon. According to the effects, activity and antioxidant properties of the active substance of cinnamon, taking into account their side effects in vitro and in silico, this active substance of the plant can be used as an inhibitor of the PI3K/AKT signaling pathway and also it can be used as a Malignant tumor preventer.
منابع و مأخذ:
Sadeghi S, Davoodvandi A, Pourhanifeh MH, Sharifi N, ArefNezhad R, Sahebnasagh R, et al. Anti-cancer effects of cinnamon: Insights into its apoptosis effects. Eur J Med Chem. 2019;178:131–40.
Azamjah N, Soltan-Zadeh Y, Zayeri F. Global trend of breast cancer mortality rate: A 25-year study. Asian Pacific J Cancer Prev. 2019;20(7):2015–20.
Momenimovahed Z, Salehiniya H. Epidemiological characteristics of and risk factors for breast cancer in the world. Breast Cancer Targets Ther. 2019;11:151–64.
Yin L, Duan JJ, Bian XW, Yu SC. Triple-negative breast cancer molecular subtyping and treatment progress. Breast Cancer Res. 2020;22(1):1–13.
Fernández MF, Reina-Pérez I, Astorga JM, Rodríguez-Carrillo A, Plaza-Díaz J, Fontana L. Breast cancer and its relationship with the microbiota. Int J Environ Res Public Health. 2018;15(8):1–20.
Zhang F, Zhang S, Hu Y, Wang N, Wu L, Ding M. Role of PI3K/AKT signaling pathway in proliferation, migration and odontogenic differentiation of human dental pulp stem cells. J Hard Tissue Biol. 2020;29(2):99–104.
Haddadi N, Lin Y, Travis G, Simpson AM, McGowan EM, Nassif NT. PTEN/PTENP1: “Regulating the regulator of RTK-dependent PI3K/Akt signalling”, new targets for cancer therapy. Mol Cancer. 2018;17(1):1–14.
Zhang H, Pan Y zhen, Cheung M, Cao M, Yu C, Chen L, et al. LAMB3 mediates apoptotic, proliferative, invasive, and metastatic behaviors in pancreatic cancer by regulating the PI3K/Akt signaling pathway. Cell Death Dis [Internet]. 2019;10(3). Available from: http://dx.doi.org/10.1038/s41419-019-1320-z
Sarkar B, Ullah A, Islam S, Hossain S. Anticancer potential of medicinal plants from Bangladesh and their effective compounds against cancer. 2019;8(3):827–33.
Nazhvani AD, Sarafraz N, Askari F, Heidari F, Razmkhah M. Anti-Cancer Effects of Traditional Medicinal Herbs on Oral Squamous Cell Carcinoma. 2020;21:479–84.
Arora S, Gusain M, Gunupuru R, Kaushik R, Sinha P, Kumar D. TITLE : CINNAMON : A CLINICAL APPROACH AS MULTIFARIOUS NATURAL REMEDY WITH. 2021;08(03):2331–45.
Alizadeh S, Esmaeili A, Omidi Y. Anti-cancer properties of Escherichia coli Nissle 1917 against HT-29 colon cancer cells through regulation of Bax/Bcl-xL and AKT/ PTEN signaling pathways. Iran J Basic Med Sci. 2020;23(7):886–93.
Sur S, Nakanishi H, Steele R, Ray RB. Depletion of PCAT-1 in head and neck cancer cells inhibits tumor growth and induces apoptosis by modulating c-Myc-AKT1-p38 MAPK signalling pathways. BMC Cancer. 2019;19(1):1–9.
Aghamohammadi D, Fakhari S, Bilehjani E, Hassanzadeh S. The Effects of Honey and Cinnamon Mixture on Improving the Quality of Life in Breast Cancer. Crescent J Med Biol Sci. 2017;4(2):74–9.
Liu Y, An T, Wan D, Yu B, Fan Y, Pei X. Targets and Mechanism Used by Cinnamaldehyde, the Main Active Ingredient in Cinnamon, in the Treatment of Breast Cancer. Front Pharmacol. 2020;11(December):1–12.
Xie GY, Ma J, Guan L, Liu XM, Wang A, Hu CH. Proliferation effects of cinnamon extract on human HeLa and HL-60 tumor cell lines. Eur Rev Med Pharmacol Sci. 2018;22(16):5347–54.
Li H, Prever L, Hirsch E, Gulluni F. Targeting PI3K/AKT/mTOR signaling pathway in breast cancer. Cancers (Basel). 2021;13(14):3517.
Chen B, Jin X, Wang H, Zhou Q, Li G, Lu X. Network Pharmacology, Integrated Bioinformatics, and Molecular Docking Reveals the Anti-Ovarian Cancer Molecular Mechanisms of Cinnamon (Cinnammomum cassia (L.) J.Presl). Natural Product communications. 2022;17(8): 1-12.
_||_
Sadeghi S, Davoodvandi A, Pourhanifeh MH, Sharifi N, ArefNezhad R, Sahebnasagh R, et al. Anti-cancer effects of cinnamon: Insights into its apoptosis effects. Eur J Med Chem. 2019;178:131–40.
Azamjah N, Soltan-Zadeh Y, Zayeri F. Global trend of breast cancer mortality rate: A 25-year study. Asian Pacific J Cancer Prev. 2019;20(7):2015–20.
Momenimovahed Z, Salehiniya H. Epidemiological characteristics of and risk factors for breast cancer in the world. Breast Cancer Targets Ther. 2019;11:151–64.
Yin L, Duan JJ, Bian XW, Yu SC. Triple-negative breast cancer molecular subtyping and treatment progress. Breast Cancer Res. 2020;22(1):1–13.
Fernández MF, Reina-Pérez I, Astorga JM, Rodríguez-Carrillo A, Plaza-Díaz J, Fontana L. Breast cancer and its relationship with the microbiota. Int J Environ Res Public Health. 2018;15(8):1–20.
Zhang F, Zhang S, Hu Y, Wang N, Wu L, Ding M. Role of PI3K/AKT signaling pathway in proliferation, migration and odontogenic differentiation of human dental pulp stem cells. J Hard Tissue Biol. 2020;29(2):99–104.
Haddadi N, Lin Y, Travis G, Simpson AM, McGowan EM, Nassif NT. PTEN/PTENP1: “Regulating the regulator of RTK-dependent PI3K/Akt signalling”, new targets for cancer therapy. Mol Cancer. 2018;17(1):1–14.
Zhang H, Pan Y zhen, Cheung M, Cao M, Yu C, Chen L, et al. LAMB3 mediates apoptotic, proliferative, invasive, and metastatic behaviors in pancreatic cancer by regulating the PI3K/Akt signaling pathway. Cell Death Dis [Internet]. 2019;10(3). Available from: http://dx.doi.org/10.1038/s41419-019-1320-z
Sarkar B, Ullah A, Islam S, Hossain S. Anticancer potential of medicinal plants from Bangladesh and their effective compounds against cancer. 2019;8(3):827–33.
Nazhvani AD, Sarafraz N, Askari F, Heidari F, Razmkhah M. Anti-Cancer Effects of Traditional Medicinal Herbs on Oral Squamous Cell Carcinoma. 2020;21:479–84.
Arora S, Gusain M, Gunupuru R, Kaushik R, Sinha P, Kumar D. TITLE : CINNAMON : A CLINICAL APPROACH AS MULTIFARIOUS NATURAL REMEDY WITH. 2021;08(03):2331–45.
Alizadeh S, Esmaeili A, Omidi Y. Anti-cancer properties of Escherichia coli Nissle 1917 against HT-29 colon cancer cells through regulation of Bax/Bcl-xL and AKT/ PTEN signaling pathways. Iran J Basic Med Sci. 2020;23(7):886–93.
Sur S, Nakanishi H, Steele R, Ray RB. Depletion of PCAT-1 in head and neck cancer cells inhibits tumor growth and induces apoptosis by modulating c-Myc-AKT1-p38 MAPK signalling pathways. BMC Cancer. 2019;19(1):1–9.
Aghamohammadi D, Fakhari S, Bilehjani E, Hassanzadeh S. The Effects of Honey and Cinnamon Mixture on Improving the Quality of Life in Breast Cancer. Crescent J Med Biol Sci. 2017;4(2):74–9.
Liu Y, An T, Wan D, Yu B, Fan Y, Pei X. Targets and Mechanism Used by Cinnamaldehyde, the Main Active Ingredient in Cinnamon, in the Treatment of Breast Cancer. Front Pharmacol. 2020;11(December):1–12.
Xie GY, Ma J, Guan L, Liu XM, Wang A, Hu CH. Proliferation effects of cinnamon extract on human HeLa and HL-60 tumor cell lines. Eur Rev Med Pharmacol Sci. 2018;22(16):5347–54.
Li H, Prever L, Hirsch E, Gulluni F. Targeting PI3K/AKT/mTOR signaling pathway in breast cancer. Cancers (Basel). 2021;13(14):3517.
Chen B, Jin X, Wang H, Zhou Q, Li G, Lu X. Network Pharmacology, Integrated Bioinformatics, and Molecular Docking Reveals the Anti-Ovarian Cancer Molecular Mechanisms of Cinnamon (Cinnammomum cassia (L.) J.Presl). Natural Product communications. 2022;17(8): 1-12.