Cancer Chemopreventive and Cytotoxic Activities of Isowithametelin from Datura innoxia
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Cancer Chemopreventive and Cytotoxic Activities of Isowithametelin from Datura innoxia Humaira Fatima 1 & Madiha Ahmed 1,2 & Muhammad Waleed Baig 1 Tamara P. Kondratyuk 4 & John M. Pezzuto 4,5 & Ihsan- ul-Haq 1
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Muhammad Nawaz Tahir 3
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Received: 27 April 2020 / Accepted: 8 September 2020 # Sociedade Brasileira de Farmacognosia 2020
Abstract Datura innoxia Mill., Solanaceae, an underexplored ethnomedicinal plant, has been empirically evaluated in the current study for the isolation of bioactive agents. A crude extract of D. innoxia leaves was subjected to normal-phase medium pressure and vacuum liquid chromatography which led to the purification of a withanolide, isowithametelin. The chemical structure was established based on single-crystal X-ray diffraction. Isowithametelin exhibited substantial cytotoxicity against tested human cancer cell lines (breast cancer MCF-7 (ATCC® HTB-22), lung carcinoma LU-1 (human lung carcinoma established in the Department of Surgical Oncology, University of Illinois at Chicago), and prostate adenocarcinoma PC-3 (ATCC® CRL-1435)) with IC50 values of 4.3 ± 0.93, 6.9 ± 1.3, and 0.01 ± 0.001 μg/ml, respectively. It also inhibited nitric oxide production in lipopolysaccharide-activated murine macrophage RAW 264.7 cells (IC50 value of 18.5 ± 1.8 μg/ml) and demonstrated moderate protein kinase inhibition. This work suggests a possible anticancer role of isowithametelin; in vivo studies remain necessary to corroborate in vitro efficacy. Keywords Isowithametelin . Cytotoxicity . TNF-α . Protein kinase inhibition . NF-κB . NO production . Solanaceae
Introduction Withanolides constitute a group of naturally occurring C-28 steroidal lactone triterpenoids assembled on an integral or reorganized ergostane nucleus, in which C-22 and C-26 are oxidized to form a δ-lactone ring. They are abundantly present Electronic supplementary material The online version of this article (https://doi.org/10.1007/s43450-020-00102-9) contains supplementary material, which is available to authorized users. * Ihsan- ul-Haq [email protected] 1
Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan
2
Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University, Islamabad 44000, Pakistan
3
Department of Physics, University of Sargodha, Sargodha, Pakistan
4
Daniel K. Inouye College of Pharmacy, University of Hawaii at Hilo, Hilo, HI 96720, USA
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College of Pharmacy and Health Sciences, Western New England University, 1215 Wilbraham Rd., Springfield, MA 01119-2684, USA
in plants of the family Solanaceae. The basic structure is designated as the withanolide skeleton, i.e., 22-hydroxy ergostane-26-oic acid 26, 22-lactones, which are generally polyoxygenated (Xu et al. 2015). Withanolides are mainly contained in leaves, and their concentration is generally low. Apart from Withania, withanolides are also distributed to other Solanaceous genera including Iochroma, Acnistus, Deprea, Datura, Lycium, Dunalis, Nicandra, Jaborosa,
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