@article{c9800d1c6af249a8a75b8549c7a76159,
title = "Identification of withaferin a as a potential candidate for anti-cancer therapy in non-small cell lung cancer",
abstract = "Low response rate and recurrence are common issues in lung cancer; thus, identifying a potential compound for these patients is essential. Utilizing an in silico screening method, we identified withaferin A (WA), a cell-permeable steroidal lactone initially extracted from Withania somnifera, as a potential anti–lung cancer and anti–lung cancer stem-like cell (CSC) agent. First, we demonstrated that WA exhibited potent cytotoxicity in several lung cancer cells, as evidenced by low IC50 values. WA concurrently induced autophagy and apoptosis and the activation of reactive oxygen species (ROS), which plays an upstream role in mediating WA-elicited effects. The increase in p62 indicated that WA may modulate the autophagy flux followed by apoptosis. In vivo research also demonstrated the anti-tumor effect of WA treatment. We subsequently demonstrated that WA could inhibit the growth of lung CSCs, decrease side population cells, and inhibit lung cancer spheroid-forming capacity, at least through downregulation of mTOR/STAT3 signaling. Furthermore, the combination of WA and chemotherapeutic drugs, including cisplatin and pemetrexed, exerted synergistic effects on the inhibition of epidermal growth factor receptor (EGFR) wild-type lung cancer cell viability. In addition, WA can further enhance the cytotoxic effect of cisplatin in lung CSCs. Therefore, WA alone or in combination with standard chemotherapy is a potential treatment option for EGFR wild-type lung cancer and may decrease the occurrence of cisplatin resistance by inhibiting lung CSCs.",
keywords = "Connectivity map, Non-small-cell lung cancer, Synergistic effect, Withaferin A",
author = "Hsu, {Jade H.M.} and Chang, {Peter M.H.} and Cheng, {Tai Shan} and Kuo, {Yu Lun} and Wu, {Alexander T.H.} and Tran, {Thu Ha} and Yang, {Yun Hsuan} and Chen, {Jing Ming} and Tsai, {Yu Chen} and Chu, {Yeh Shiu} and Huang, {Tse Hung} and Huang, {Chi Ying F.} and Lai, {Jin Mei}",
note = "Funding Information: This research was supported by a grant from Taiwan Clinical Oncology Research Foundation, Taipei Veterans General Hospital (V107C-005), and the Ministry of Science and Technology (MOST), Taiwan (MOST-106-2627-M-075-001) to Peter Mu-Hsin Chang, Chang-Gung Memorial Hospital Research Foundation(CMRPG2C0491-2, CMRPG2D0091-2, and CMRPG2G0332), and MOST 107-2320-B-182A-007 to T. H. Huang, Chang-Gung Memorial Hospital Research Foundation (CMRPG2G0332) and MOST 107-2320-B-010-040-MY3 to Chi-Ying F. Huang, and MOST-106-2627-M-030-001, MOST-107-2627-M-030-001 to Jin-Mei Lai. Funding Information: Acknowledgment: This work was financially supported by the Brain Research Center, National Yang-Ming University from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan. Funding Information: Funding: This research was supported by a grant from Taiwan Clinical Oncology Research Foundation, Taipei Veterans General Hospital (V107C-005), and the Ministry of Science and Technology (MOST), Taiwan (MOST-106-2627-M-075-001) to Peter Mu-Hsin Chang, Chang-Gung Memorial Hospital Research Foundation (CMRPG2C0491-2, CMRPG2D0091-2, and CMRPG2G0332), and MOST107-2320-B-182A-007 to T. H. Huang, Chang-Gung Memorial Hospital Research Foundation (CMRPG2G0332) and MOST107-2320-B-010-040-MY3 to Chi-Ying F. Huang, and MOST-106-2627-M-030-001, MOST-107-2627-M-030-001 to Jin-Mei Lai. Publisher Copyright: {\textcopyright} 2019 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2019",
month = jul,
day = "1",
doi = "10.3390/cancers11071003",
language = "English",
volume = "11",
journal = "Cancers",
issn = "2072-6694",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "7",
}