Synergistic Antitumor and Apoptotic Activity of Sitagliptin or Linagliptin Plus Cisplatin Against A549 Lung Cancer Cells (An Invitro Study)

被引:0
|
作者
Al Khafaji, Ameer M. [1 ]
Bairam, Ahsan F. [1 ]
机构
[1] Univ Kufa, Fac Pharm, Dept Pharmacol & Toxicol, Najaf, Iraq
来源
JOURNAL OF CONTEMPORARY MEDICAL SCIENCES | 2024年 / 10卷 / 03期
关键词
Antitumor; A549 cell line; sitagliptin; linagliptin; MTT assay; DIPEPTIDYL PEPTIDASE-4 INHIBITOR; BCL-2; FAMILY-MEMBERS; COLON-CANCER; RISK; IV;
D O I
10.22317/jcms.v10i3.1555
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: Lung cancer (LC) has the highest mortality rate globally. Most chemotherapeutic medicines now in use are cytotoxic, prompting the search for novel compounds with anticancer properties and improved safety profiles for normal cells. Dipeptidyl peptidase-4 inhibitors have demonstrated anticancer effects and apoptotic properties by specifically inhibiting dipeptidyl peptidase -4, a glycoprotein found in various organs that support the spread of cancer and tumor formation. Based on that, this study aimed to evaluate the cytotoxicity and apoptotic activity of sitagliptin (SITA) and linagliptin (LINA) against the lung cancer cell line (A549) alone and in combination with cisplatin (CP). Methods: A549 cells were categorized into six groups: control (untreated cells), CP-treated cells, SITA-treated cells, LINA-treated cells, CP plus SITA treated cells (1:1 ratio), and CP plus LINA treated cells (1:1 ratio). After 72 hours of incubation, cell viability (or cytotoxicity) and concentration required to inhibit 50% of cell viability (IC50) for each group were determined using an MTT assay. This method is safe and easy to use, has more reproducibility, and is commonly used for cell viability and cytotoxicity tests. Later, A549 cells were cultured in six flasks and exposed to the IC50 for 36 hours. Afterward, the cells were harvested and centrifuged, and the supernatant was removed. The remaining cell pellets were collected and lysed using a lysis buffer to measure B-cell lymphoma type 2 (BCL-2) levels with ELISA test kits. The data was collected and subjected to statistical analysis techniques. Results: MTT assay results determined that SITA and LINA significantly increased A549 cell cytotoxicity compared to the control group (P<0.0001). Moreover, combining SITA or LINA with CP showed markedly increased antitumor efficacy and more significant cytotoxicity directed toward A549 cells. Additionally, these combinations highly reduced IC50 in comparison to monotherapy. Considerably, both drugs showed remarkable apoptotic activity on A549 cells when used alone or combined with CP by decreasing BCL2 levels. Consequently, it potentiates apoptotic effects and cytotoxicity of CP against cancer cells. Interestingly, Lina was more potent than Sita regarding cytotoxicity and apoptotic activity on A549 cells. Conclusion: SITA and Lina exhibited significant cytotoxic and apoptotic effects against A549 cells through the induction of apoptosis. Notably, the results suggest a potential synergistic anticancer impact on CP.
引用
收藏
页码:228 / 234
页数:7
相关论文
共 50 条
  • [21] THE ASSESSMENT OF A549 LUNG CANCER CELLS RESPONSE TO CISPLATIN CONSIDERING CYTOSKELETAL ORGANIZATION
    Szczepanski, Mariusz Andrzej
    Grzanka, Alina
    Litwiniec, Anna
    Gackowska, Lidia
    Kubiszewska, Izabela
    Grzanka, Dariusz
    CYTOMETRY PART B-CLINICAL CYTOMETRY, 2009, 76B (06) : 431 - 432
  • [22] Dehydrobruceine B enhances the cisplatin-induced cytotoxicity through regulation of the mitochondrial apoptotic pathway in lung cancer A549 cells
    Huang, Zhuqing
    Yang, Guotao
    Shen, Tao
    Wang, Xiaoning
    Li, Haizhen
    Ren, Dongmei
    BIOMEDICINE & PHARMACOTHERAPY, 2017, 89 : 623 - 631
  • [23] Synthesis of pyrazole peptidomimetics and their inhibition against A549 lung cancer cells
    Liu, Ying-Rui
    Luo, Ji-Zhuang
    Duan, Pan-Pan
    Shao, Jing
    Zhao, Bao-Xiang
    Miao, Jun-Ying
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2012, 22 (22) : 6882 - 6887
  • [24] Antitumor activity of cobrotoxin in human lung adenocarcinoma A549 cells and transplantation in nude mouse
    He, Jingkang
    Xie, Yan
    Han, Rong
    Qin, Zhenghong
    INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 2014, 34 : S16 - S16
  • [25] Selenium potentiates the antitumor activity of radiation therapy in human A549 lung cancer xenografts
    Yan, G. Y.
    Durrani, F. A.
    Cao, S.
    Park, Y.
    Thompson, G. M.
    Martin, J. L.
    Jaggemauth, W.
    Rustum, Y. M.
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2007, 69 (03): : S597 - S598
  • [26] Antitumor activity of interleukin-18 on A549 human lung cancer cell line
    Xiong, Donglan
    Feng, Rui
    Yang, Sheng
    Lin, Tingyan
    Chen, Xiangqi
    JOURNAL OF CANCER RESEARCH AND THERAPEUTICS, 2019, 15 (07) : 1635 - 1641
  • [27] Apoptotic effect of astaxanthin from white shrimp shells on lung cancer A549 cells
    Tanasawet, Supita
    Sukketsiri, Wanida
    Chonpathompikunlert, Pennapa
    Klaypradit, Wanwimol
    Sroyraya, Morakot
    Hutamekalin, Pilaiwanwadee
    TROPICAL JOURNAL OF PHARMACEUTICAL RESEARCH, 2020, 19 (09) : 1835 - 1842
  • [28] Apoptotic Effect of Cissus Quadrangularis Ethanolic Extract on A549 Human Lung Cancer Cells
    Gurumurthy, Kaviyaselvi
    Raghunandhakumar, S.
    Ezhilarasan, D.
    Lakshmi, T.
    JOURNAL OF COMPLEMENTARY MEDICINE RESEARCH, 2021, 12 (03): : 54 - 60
  • [29] Study on the chemical constituents of various water chestnuts and their activity against anti-lung cancer A549 cells in vitro
    Mao, Zhifang
    Wang, Qing
    Cheng, Faxiu
    Zhang, Zhiyong
    Cary
    Kang, Gongli
    Li, Ying
    PRZEMYSL CHEMICZNY, 2019, 98 (02): : 204 - 207
  • [30] Investigation of the mechanism and apoptotic pathway induced by 4β cinnamido linked podophyllotoxins against human lung cancer cells A549
    Kamal, Ahmed
    Nayak, V. Lakshma
    Bagul, Chandrakant
    Vishnuvardhan, M. V. P. S.
    Mallareddy, Adla
    APOPTOSIS, 2015, 20 (11) : 1518 - 1529