Scorpion Venom-Functionalized Quercetin Phytosomes for Breast Cancer Management: In Vitro Response Surface Optimization and Anticancer Activity against MCF-7 Cells

被引:30
作者
Alhakamy, Nabil A. [1 ,2 ,3 ]
Fahmy, Usama A. [1 ]
Eldin, Shaimaa M. Badr [1 ,4 ]
Ahmed, Osama A. A. [1 ]
Aldawsari, Hibah M. [1 ,2 ]
Okbazghi, Solomon Z. [5 ]
Alfaleh, Mohamed A. [1 ,6 ]
Abdulaal, Wesam H. [7 ]
Alamoudi, Abdulmohsin J. [8 ]
Mady, Fatma M. [9 ]
机构
[1] King Abdulaziz Univ, Fac Pharm, Dept Pharmaceut, Jeddah 21589, Saudi Arabia
[2] King Abdulaziz Univ, Ctr Excellence Drug Res & Pharmaceut Ind, Jeddah 21589, Saudi Arabia
[3] King Abdulaziz Univ, Mohamed Saeed Tamer Chair Pharmaceut Ind, Jeddah 21589, Saudi Arabia
[4] Cairo Univ, Dept Pharmaceut & Ind Pharm, Cairo 11562, Egypt
[5] Alex Pharmaceut, Global Analyt & Pharmaceut Dev, New Haven, CT 06510 USA
[6] King Abdulaziz Univ, King Fahd Med Res Ctr, Vaccines & Immunotherapy Unit, Jeddah 21589, Saudi Arabia
[7] King Abdulaziz Univ, King Fahd Med Res Ctr, Fac Sci, Dept Biochem,Canc & Mutagenesis Unit, Jeddah 21589, Saudi Arabia
[8] King Abdulaziz Univ, Fac Pharm, Dept Pharmacol & Toxicol, Jeddah 21589, Saudi Arabia
[9] Minia Univ, Fac Pharm, Dept Pharmaceut, Al Minya 61519, Egypt
关键词
breast cancer; nanoparticles; apoptosis; nanocomplex; optimization; DRUG-DELIVERY SYSTEMS; PHOSPHOLIPID COMPLEX; NANOPARTICLES; CYTOTOXICITY; APOPTOSIS; RECEPTOR; CHARGE; EXPRESSION; INDUCTION; LIPOSOMES;
D O I
10.3390/polym14010093
中图分类号
O63 [高分子化学(高聚物)];
学科分类号
070305 ; 080501 ; 081704 ;
摘要
Breast cancer is a dangerous type of cancer in women. Quercetin (QRT), a naturally occurring flavonoid, has wide biological effects including antioxidant, anticarcinogenic, anti-inflammatory, antiallergic, and antiviral activities. The anticancer activity is considered the most valuable effect of QRT against several types of cancer, including prostate, liver, lung, colon, and breast cancer. Scorpion venom peptides (SV) has been found to induce apoptosis and aggravate cancer cells, making it a promising anticancer agent. QRT, SV, and Phospholipon(R) 90H (PL) were incorporated in a nano-based delivery platform to assess QRT's cellular uptake and antiproliferative efficacy against a lung cancer cell line derived from human breast cancer cells MCF-7. Several nanovesicles were prepared and optimized, using four-factor Box-Behnken, in an experimental design. The optimized phytosomes showed vesicle size and zeta potential values of 116.9 nm and 31.5 mV, respectively. The IC50 values revealed that MCF-7 cells were significantly more sensitive to the optimized QRT formula than the plain formula and raw QRT. Cell cycle analysis revealed that optimized QRT formula treatment resulted in significant cell cycle arrest at the S phase. The results also indicated that treatment with QRT formula significantly increased caspase-9, Bax, Bcl-2, and p53 mRNA expression, compared with the plain formula and QRT. In terms of the inflammatory markers, the QRT formula significantly reduced the activity of TNF-alpha and NF-kappa B, in comparison with the plain formula and QRT only. Overall, the findings from the study proved that a QRT formulation could be a promising therapeutic approach for the treatment of breast cancer.
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页数:21
相关论文
共 56 条
[1]  
Aguirre L., 2011, The Open Nutraceuticals Journal, V4, DOI DOI 10.2174/1876396001104010189
[2]   Development of an optimized avanafil-loaded invasomal transdermal film: Ex vivo skin permeation and in vivo evaluation [J].
Ahmed, Osama A. A. ;
Badr-Eldin, Shaimaa M. .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2019, 570
[3]  
Akef H, 2017, J CANCER PREV, V22, P40, DOI 10.15430/JCP.2017.22.1.40
[4]   RETRACTED: Optimized Icariin Phytosomes Exhibit Enhanced Cytotoxicity and Apoptosis-Inducing Activities in Ovarian Cancer Cells (Retracted Article) [J].
Alhakamy, Nabil A. ;
Fahmy, Usama A. ;
Badr-Eldin, Shaimaa M. ;
Ahmed, Osama A. A. ;
Asfour, Hani Z. ;
Aldawsari, Hibah M. ;
Algandaby, Mardi M. ;
Eid, Basma G. ;
Abdel-Naim, Ashraf B. ;
Awan, Zuhier A. ;
Alruwaili, Nabil K. ;
Mohamed, Amir I. .
PHARMACEUTICS, 2020, 12 (04)
[5]   Encapsulation of Lovastatin in Zein Nanoparticles Exhibits Enhanced Apoptotic Activity in HepG2 Cells [J].
Alhakamy, Nabil A. ;
Ahmed, Osama A. A. ;
Aldawsari, Hibah M. ;
Alfaifi, Mohammad Y. ;
Eid, Basma G. ;
Abdel-Naim, Ashraf B. ;
Fahmy, Usama A. .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2019, 20 (22)
[6]   A Comparative Study of the Anticancer Activity and PARP-1 Inhibiting Effect of Benzofuran-Pyrazole Scaffold and Its Nano-Sized Particles in Human Breast Cancer Cells [J].
Anwar, Manal M. ;
Abd El-Karim, Somaia S. ;
Mahmoud, Ahlam H. ;
Amr, Abd El-Galil E. ;
Al-Omar, Mohamed A. .
MOLECULES, 2019, 24 (13)
[7]   Optimized semisolid self-nanoemulsifying system based on glyceryl behenate: A potential nanoplatform for enhancing antitumor activity of raloxifene hydrochloride in MCF-7 human breast cancer cells [J].
Badr-Eldin, Shaimaa M. ;
Aldawsari, Hibah M. ;
Ahmed, Osama A. A. ;
Alhakamy, Nabil A. ;
Neamatallah, Thikryat ;
Okbazghi, Solomon Z. ;
Fahmy, Usama A. .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2021, 600
[8]  
Bombardelli E., 1989, Fitoterapia, V60, P1
[9]   Quercetin in Cancer Treatment, Alone or in Combination with Conventional Therapeutics? [J].
Brito, Ana Filipa ;
Ribeiro, Marina ;
Abrantes, Ana Margarida ;
Pires, Ana Salome ;
Teixo, Ricardo Jorge ;
Tralhao, Jose Guilherme ;
Botelho, Maria Filomena .
CURRENT MEDICINAL CHEMISTRY, 2015, 22 (26) :3025-3039
[10]   Induction of death receptor 5 and suppression of survivin contribute to sensitization of TRAIL-induced cytotoxicity by quercetin in non-small cell lung cancer cells [J].
Chen, Wenshu ;
Wang, Xia ;
Zhuang, Jianguo ;
Zhang, Lin ;
Lin, Yong .
CARCINOGENESIS, 2007, 28 (10) :2114-2121