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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

ALK and ERBB2 Protein Inhibition is Involved in the Prevention of Lung Cancer Development by Vincamine

Author(s): Aarti Verma, Poonam Yadav, Sonu Rajput, Saloni Verma, Sahil Arora, Raj Kumar, Jasvinder Singh Bhatti, Amit Khurana and Umashanker Navik*

Volume 23, Issue 13, 2023

Published on: 19 April, 2023

Page: [1587 - 1595] Pages: 9

DOI: 10.2174/1871520623666230412102532

Price: $65

Abstract

Background: According to the WHO report of 2022, 2.21 million new cases and 1.80 million deaths were reported for lung cancer in the year 2020. Therefore, there is an urgent need to explore novel, safe, and effective therapeutic interventions for lung cancer.

Objective: To find the potential targets of vincamine using a network pharmacology approach and docking studies and to evaluate the anti-cancer effect of vincamine on A549 cell line.

Methods: Hence, in the present study, we explored the anti-cancer potential of vincamine by using network pharmacology, molecular docking, and in vitro approaches. Network pharmacology demonstrated that the most common targets of vincamine are G-protein coupled receptors, cytosolic proteins, and enzymes. Among these targets, two targets, ALK and ERBB2 protein, were common between vincamine and non-small cell lung cancer.

Results: We discovered a link between these two targets and their companion proteins, as well as cancer-related pathways. In addition, a docking investigation between the ligand for vincamine and two targeted genes revealed a strong affinity toward these targeted proteins. Further, the in vitro study demonstrated that vincamine treatment for 72 h led to dosedependent (0-500 μM) cytotoxicity on the A549 lung cancer cell line with an IC50 value of 291.7 μΜ. The wound-healing assay showed that vincamine treatment (150 and 300 μM) significantly inhibited cell migration and invasion. Interestingly, acridine orange/ethidium bromide dual staining demonstrated that vincamine treatment induces apoptosis in A549 cells. Additionally, the dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay showed an increased level of reactive oxygen species (ROS) after the vincamine treatment, indicating ROS-mediated apoptosis in A549 cells.

Conclusion: Altogether, based on our findings, we hypothesize that vincamine-induced apoptosis of lung cancer cells via ALK and ERBB2 protein modulation may be an attractive futuristic strategy for managing lung cancer in combination with chemotherapeutic agents to obtain synergistic effects with reduced side effects.

Keywords: Vincamine, network pharmacology, docking study, lung cancer, ROS, apoptosis

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[1]
WHO. Cancer 2022. Available from: https://www.who.int/news-room/fact-sheets/detail/cancer
[2]
Zheng, M. Classification and pathology of lung cancer. Surg. Oncol. Clin., 2016, 25(3), 447-468.
[PMID: 27261908]
[3]
Amaani, R.; Dwira, S. In Journal of Physics: Conference Series; IOP Publishing, Bristol, UK, 2018, 1073, p. 032042.
[4]
Surya, K.D. Fundamentals of Cancer Detection, Treatment, and Prevention. In: Pharmacology & Pharmaceutical Medicine; Springer Berlin, Heidelberg, pp. 536.
[5]
Brambilla, E.; Gazdar, A. Pathogenesis of lung cancer signalling pathways: Roadmap for therapies. Eur. Respir. J., 2009, 33(6), 1485-1497.
[http://dx.doi.org/10.1183/09031936.00014009] [PMID: 19483050]
[6]
Ou, S.H.I.; Shirai, K. Anaplastic lymphoma kinase (ALK) signaling in lung cancer. Adv. Exp. Med. Biol., 2016, 893, 179-187.
[http://dx.doi.org/10.1007/978-3-319-24223-1_9] [PMID: 26667344]
[7]
Dhyani, P.; Quispe, C.; Sharma, E.; Bahukhandi, A.; Sati, P.; Attri, D.C.; Szopa, A.; Sharifi-Rad, J.; Docea, A.O.; Mardare, I.; Calina, D.; Cho, W.C. Anti-cancer potential of alkaloids: A key emphasis to colchicine, vinblastine, vincristine, vindesine, vinorelbine and vincamine. Cancer Cell Int., 2022, 22(1), 206.
[http://dx.doi.org/10.1186/s12935-022-02624-9] [PMID: 35655306]
[8]
Fandy, T.E.; Abdallah, I.; Khayat, M.; Colby, D.A.; Hassan, H.E. In vitro characterization of transport and metabolism of the alkaloids: Vincamine, vinpocetine and eburnamonine. Cancer Chemother. Pharmacol., 2016, 77(2), 259-267.
[http://dx.doi.org/10.1007/s00280-015-2924-3] [PMID: 26666648]
[9]
Patangrao, R.A.; Kumar, B.A.; Kumar, B.K.; Mekala, L.; Mahesh, K.J.; Neeradi, D.; Durga, V.H.D.; Gadige, A.; Khurana, A. Vincamine, an active constituent of Vinca rosea ameliorates experimentally induced acute lung injury in Swiss albino mice through modulation of Nrf-2/NF-κB signaling cascade. Int. Immunopharmacol., 2022, 108, 108773.
[http://dx.doi.org/10.1016/j.intimp.2022.108773] [PMID: 35453074]
[10]
Al-Rashed, S.; Baker, A.; Ahmad, S.S.; Syed, A.; Bahkali, A.H.; Elgorban, A.M.; Khan, M.S. Vincamine, a safe natural alkaloid, represents a novel anti-cancer agentt. Bioorg. Chem., 2021, 107, 104626.
[http://dx.doi.org/10.1016/j.bioorg.2021.104626] [PMID: 33450545]
[11]
Xie, B.; Lu, H.; Xu, J.; Luo, H.; Hu, Y.; Chen, Y.; Geng, Q.; Song, X.J.J.B.S. Targets of hydroxychloroquine in the treatment of rheumatoid arthritis. A network pharmacology study. Joint Bone Spine, 2021, 88(2), 105099.
[12]
Arora, S.; Joshi, G.; Kalra, S.; Wani, A.A.; Bharatam, P.V.; Kumar, P.; Kumar, R. Knoevenagel/tandem knoevenagel and michael adducts of cyclohexane-1, 3-dione and aryl aldehydes: synthesis, DFT studies, xanthine oxidase inhibitory potential, and molecular modeling. ACS Omega, 2019, 4(3), 4604-4614.
[http://dx.doi.org/10.1021/acsomega.8b03060]
[13]
Tominaga, H.; Ishiyama, M.; Ohseto, F.; Sasamoto, K.; Hamamoto, T.; Suzuki, K.; Watanabe, M.J.A.C. A water-soluble tetrazolium salt useful for colorimetric cell viability assay. Anal. Commun., 1999, 36, 47-50.
[http://dx.doi.org/10.1039/a809656b]
[14]
Li, F.F.; Zhang, H.; Li, J.J.; Cao, Y.N.; Dong, X.; Gao, C.J.M.M.R. Interaction with adipocytes induces lung adenocarcinoma A549 cell migration and tumor growth. Euro. Comm. Invent. NAMs Respirat. Tract. dis., 2018, 18(2), 1973-1980.
[http://dx.doi.org/10.3892/mmr.2018.9226]
[15]
Shrivastava, S.; Jeengar, M.K.; Reddy, V.S.; Reddy, G.B.; Naidu, V.J.E. Anti-cancer effect of celastrol on human triple negative breast cancer: Possible involvement of oxidative stress, mitochondrial dysfunction, apoptosis and PI3K/Akt pathways. Exp. Mol. Pathol., 2015, 98(3), 313-327.
[16]
Kaja, S.; Payne, A.J.; Naumchuk, Y.; Levy, D.; Zaidi, D.H.; Altman, A.M.; Nawazish, S.; Ghuman, J.K.; Gerdes, B.C.; Moore, M.A.J.E.r. Plate reader-based cell viability assays for glioprotection using primary rat optic nerve head astrocytes. Exp. Eye Res., 2015, 138, 159-166.
[http://dx.doi.org/10.1016/j.exer.2015.05.023]
[17]
Fernando, D.; Adhikari, A.; Nanayakkara, C.; de Silva, E.D.; Wijesundera, R.; Soysa, P.J.B.c. Cytotoxic effects of ergone, a compound isolated from Fulviformes fastuosus. BMC Complement. Altern. Med., 2016, 16(1), 484.
[18]
Mortezaee, K.; Salehi, E.; Mirtavoos-mahyari, H.; Motevaseli, E.; Najafi, M.; Farhood, B.; Rosengren, R.J.; Sahebkar, A. Mechanisms of apoptosis modulation by curcumin: Implications for cancer therapy. J. Cell. Physiol., 2019, 234(8), 12537-12550.
[http://dx.doi.org/10.1002/jcp.28122] [PMID: 30623450]
[19]
Buja, L.M.; Eigenbrodt, M.L.; Eigenbrodt, E.H. Apoptosis and necrosis. Basic types and mechanisms of cell death. Arch. Pathol. Lab. Med., 1993, 117(12), 1208-1214.
[PMID: 8250690]
[20]
Dey, P.; Kundu, A.; Chakraborty, H.J.; Kar, B.; Choi, W.S.; Lee, B.M.; Bhakta, T.; Atanasov, A.G.; Kim, H.S. Therapeutic value of steroidal alkaloids in cancer: Current trends and future perspectives. Int. J. Cancer, 2019, 145(7), 1731-1744.
[http://dx.doi.org/10.1002/ijc.31965] [PMID: 30387881]
[21]
Woods, J.R.; Riofski, M.V.; Zheng, M.M.; O’Banion, M.A.; Mo, H.; Kirshner, J.; Colby, D.A. Synthesis of 15-methylene-eburnamonine from (+)-vincamine, evaluation of anti-cancer activity, and investigation of mechanism of action by quantitative NMR. Bioorg. Med. Chem. Lett., 2013, 23(21), 5865-5869.
[http://dx.doi.org/10.1016/j.bmcl.2013.08.095] [PMID: 24055047]
[22]
Sprumont, P.; Lintermans, J. Autoradiographic evidence for passage of vincamine through the blood-brain barrier. Arch. Int. Pharmacodyn. Ther., 1979, 237(1), 42-48.
[PMID: 485685]
[23]
Sullivan, I.; Planchard, D. ALK inhibitors in non-small cell lung cancer: The latest evidence and developments. Ther. Adv. Med. Oncol., 2016, 8(1), 32-47.
[http://dx.doi.org/10.1177/1758834015617355] [PMID: 26753004]
[24]
Arbour, K.C.; Riely, G.J. Diagnosis and treatment of anaplastic lymphoma kinase–positive non–small cell lung cancer. Hematol. Oncol. Clin. North Am., 2017, 31(1), 101-111.
[http://dx.doi.org/10.1016/j.hoc.2016.08.012] [PMID: 27912826]
[25]
Zeng, J.; Ma, W.; Young, R.B.; Li, T. Targeting HER2 genomic alterations in non-small cell lung cancer. J. Nat. Cancer Center, 2021, 1(2), 58-73.
[http://dx.doi.org/10.1016/j.jncc.2021.04.001]
[26]
Yu, X.; Ji, X.; Su, C. HER2-altered non-small cell lung cancer: Biology; Clinicopathologic features, and emerging therapies. Front. Oncol., 2022, 12, 860313.
[27]
Freitas, J.T.; Jozic, I.; Bedogni, B. Wound healing assay for melanoma cell migration. Methods Mol. Biol., 2021, 2265, 65-71.
[http://dx.doi.org/10.1007/978-1-0716-1205-7_4] [PMID: 33704705]
[28]
Yang, S.; Li, X.; Dou, H.; Hu, Y.; Che, C.; Xu, D. Sesamin induces A549 cell mitophagy and mitochondrial apoptosis via a reactive oxygen species-mediated reduction in mitochondrial membrane potential. Korean J. Physiol. Pharmacol., 2020, 24(3), 223-232.
[http://dx.doi.org/10.4196/kjpp.2020.24.3.223]

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