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Novel 1,3,4-oxadiazole Targets STAT3 Signaling to Induce Antitumor Effect in Lung Cancer

Molecular Biomedicine Laboratory, Postgraduate Department of Studies and Research in Biotechnology, Sahyadri Science College, Kuvempu University, Shivamogga, Karnataka 577203, India
Laboratory of Chemical Biology, Department of Studies in Organic Chemistry, University of Mysore, Manasagangotri, Mysore, Karnataka 570006, India
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612, USA
Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
Adichunchanagiri Institute for Molecular Medicine, AIMS Campus, B. G. Nagar, Nagamangala Taluk, Mandya District 571448, India
Department of Studies in Molecular Biology, University of Mysore, Manasagangotri, Mysore, Karnataka 570006, India
Institution of Excellence, Vijnana Bhavan, University of Mysore, Mysore 570006, India
Authors to whom correspondence should be addressed.
These authors contributed equally.
Biomedicines 2020, 8(9), 368;
Received: 15 June 2020 / Revised: 6 August 2020 / Accepted: 7 August 2020 / Published: 21 September 2020
Lung cancer is the leading type of malignancy in terms of occurrence and mortality in the global context. STAT3 is an oncogenic transcription factor that is persistently activated in many types of human malignancies, including lung cancer. In the present report, new oxadiazole conjugated indazoles were synthesized and examined for their anticancer potential in a panel of cancer cell lines. Among the new compounds, 2-(3-(6-chloro-5-methylpyridin-3-yl)phenyl)-5-(1-methyl-1H-indazol-3-yl)-1,3,4-oxadiazole (CHK9) showed consistently good cytotoxicity towards lung cancer cells with IC50 values ranging between 4.8–5.1 µM. The proapoptotic effect of CHK9 was further demonstrated by Annexin-FITC staining and TUNEL assay. In addition, the effect of CHK9 on the activation of STAT3 in lung cancer cells was examined. CHK9 reduced the phosphorylation of STAT3Y705 in a dose-dependent manner. CHK9 had no effect on the activation and expression of JAK2 and STAT5. It also reduced the STAT3-dependent luciferase reporter gene expression. CHK9 increased the expression of proapoptotic (p53 and Bax) proteins and decreased the expression of the antiapoptotic (Bcl-2, Bcl-xL, BID, and ICAM-1) proteins. CHK9 displayed a significant reduction in the number of tumor nodules in the in vivo lung cancer model with suppression of STAT3 activation in tumor tissues. CHK9 did not show substantial toxicity in the normal murine model. Overall, CHK9 inhibits the growth of lung cancer cells and tumors by interfering with the STAT3 signaling pathway. View Full-Text
Keywords: lung cancer; antitumor; STAT3; apoptosis lung cancer; antitumor; STAT3; apoptosis
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MDPI and ACS Style

Malojirao, V.H.; Girimanchanaika, S.S.; Shanmugam, M.K.; Sherapura, A.; Dukanya; Metri, P.K.; Vigneshwaran, V.; Chinnathambi, A.; Alharbi, S.A.; Rangappa, S.; Mohan, C.D.; Basappa; Prabhakar, B.T.; Rangappa, K.S. Novel 1,3,4-oxadiazole Targets STAT3 Signaling to Induce Antitumor Effect in Lung Cancer. Biomedicines 2020, 8, 368.

AMA Style

Malojirao VH, Girimanchanaika SS, Shanmugam MK, Sherapura A, Dukanya, Metri PK, Vigneshwaran V, Chinnathambi A, Alharbi SA, Rangappa S, Mohan CD, Basappa, Prabhakar BT, Rangappa KS. Novel 1,3,4-oxadiazole Targets STAT3 Signaling to Induce Antitumor Effect in Lung Cancer. Biomedicines. 2020; 8(9):368.

Chicago/Turabian Style

Malojirao, Vikas H., Swamy S. Girimanchanaika, Muthu K. Shanmugam, Ankith Sherapura, Dukanya, Prashant K. Metri, Vellingiri Vigneshwaran, Arunachalam Chinnathambi, Sulaiman A. Alharbi, Shobith Rangappa, Chakrabhavi D. Mohan, Basappa, Bettadathunga T. Prabhakar, and Kanchugarakoppal S. Rangappa 2020. "Novel 1,3,4-oxadiazole Targets STAT3 Signaling to Induce Antitumor Effect in Lung Cancer" Biomedicines 8, no. 9: 368.

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