Oxazine drug-seed induces paraptosis and apoptosis through reactive oxygen species/JNK pathway in human breast cancer cells

Oxazine drug-seed induces paraptosis and apoptosis through reactive oxygen species/JNK pathway in human breast cancer cells Научная публикация

Журнал

Translational Oncology
ISSN: 1944-7124

Вых. Данные

Год: 2024, Том: 49, Номер статьи : 102101, Страниц : DOI: 10.1016/j.tranon.2024.102101

Авторы

Kim Na Young ¹ , Dukanya Dukanya ² , Sethi Gautam ³ , Girimanchanaika Swamy S ² , Yang Jirui ⁴ , Nagaraja Omantheswara ⁵ , Swamynayaka Ananda ⁵ , Vishwanath Divakar ² , Venkantesha Keerthikumara ⁵ , Basappa Shreeja ⁶ , Chinnathambi Arunachalam ⁷ , Alharbi Sulaiman Ali ⁷ , Madegowda Mahendra ⁵ , Sukhorukov Alexey ⁸ , Pandey Vijay ⁹ , Lobie Peter E ¹⁰ , Basappa Basappa ¹¹ , Ahn Kwang Seok ¹²

Организации

1	Department of Science in Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
2	Laboratory of Chemical Biology, Department of Studies in Organic Chemistry, University of Mysore, Manasagangotri, Mysuru-570006, India.
3	Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 16 Medical Drive, 117600, Singapore.
4	Tsinghua Berkeley Shenzhen Institute, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen-518055, Guangdong, China.
5	Department of Studies in Physics, University of Mysore, Manasagangotri, Mysuru-570006, India.
6	Department of Chemistry, BITS-Pilani Hyderabad Campus, Jawahar Nagar, Medchal-500078, India.
7	Department of Botany and Microbiology, College of Science, King Saud University, PO Box-2455, Riyadh 11451, Saudi Arabia.
8	N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect, 47, Moscow, 119991, Russia.
9	Tsinghua Berkeley Shenzhen Institute, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen-518055, Guangdong, China; Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen, International Graduate School, Tsinghua University, Shenzhen-518055, Guangdong, China.
10	Tsinghua Berkeley Shenzhen Institute, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen-518055, Guangdong, China; Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen, International Graduate School, Tsinghua University, Shenzhen-518055, Guangdong, China; Shenzhen Bay Laboratory, Shenzhen 518055, Guangdong, China. Electronic address: pelobie@sz.tsinghua.edu.cn.
11	Laboratory of Chemical Biology, Department of Studies in Organic Chemistry, University of Mysore, Manasagangotri, Mysuru-570006, India. Electronic address: basappa@chemistry.uni-mysore.ac.in.
12	Department of Science in Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea. Electronic address: ksahn@khu.ac.kr.

Small molecule-driven JNK activation has been found to induce apoptosis and paraptosis in cancer cells. Herein pharmacological effects of synthetic oxazine (4aS, 7aS)-3-((4-(4‑chloro-2-fluorophenyl)piperazin-1-yl)methyl)-4-phenyl-4, 4a, 5, 6, 7, 7a-hexahydrocyclopenta[e] [1,2]oxazine (FPPO; BSO-07) on JNK-driven apoptosis and paraptosis has been demonstrated in human breast cancer (BC) MDA-MB231 and MCF-7 cells respectively. BSO-07 imparted significant cytotoxicity in BC cells, induced activation of JNK, and increased intracellular reactive oxygen species (ROS) levels. It also enhanced the expression of apoptosis-associated proteins like PARP, Bax, and phosphorylated p53, while decreasing the levels of Bcl-2, Bcl-xL, and Survivin. Furthermore, the drug altered the expression of proteins linked to paraptosis, such as ATF4 and CHOP. Treatment with N-acetyl-cysteine (antioxidant) or SP600125 (JNK inhibitor) partly reversed the effects of BSO-07 on apoptosis and paraptosis. Advanced in silico bioinformatics, cheminformatics, density Fourier transform and molecular electrostatic potential analysis further demonstrated that BSO-07 induced apoptosis and paraptosis via the ROS/JNK pathway in human BC cells.

Kim N.Y. , Dukanya D. , Sethi G. , Girimanchanaika S.S. , Yang J. , Nagaraja O. , Swamynayaka A. , Vishwanath D. , Venkantesha K. , Basappa S. , Chinnathambi A. , Alharbi S.A. , Madegowda M. , Sukhorukov A. , Pandey V. , Lobie P.E. , Basappa B. , Ahn K.S.
Oxazine drug-seed induces paraptosis and apoptosis through reactive oxygen species/JNK pathway in human breast cancer cells
Translational Oncology. 2024. V.49. 102101 . DOI: 10.1016/j.tranon.2024.102101 OpenAlex

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W4401673290

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