Comparative computational and experimental analyses of some natural small molecules to restore transcriptional activation function of p53 in cancer cells harbouring wild type and p53Ser46 mutant

Shefrin, Seyad; Sari, Anissa Nofita; Kumar, Vipul; Zhang, Huayue; Meidinnia, Hazna Noor; Kaul, Sunil C.; Wadhwa, Renu; Sundar, Durai

doi:10.1016/j.crstbi.2022.09.002

Cited by 4 publications

(3 citation statements)

References 56 publications

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“…Further, WN docked mortalin onto the p53 binding site, removed mortalin p53 complex and reactivated p53 which results in cell growth arrest in the case of MCF‐7, U2OS, and HT1080 at conc. 5–15 μg/mL (Table 4) (Grover, Priyandoko, et al, 2012; Malik et al, 2021; Shefrin et al, 2022; Vaishnavi et al, 2012). It was demonstrated recently that WA possess the ability to trigger apoptosis in cancer cells by activating the tumor suppressor protein p53, causing inhibition of the cell cycle (Figure 2).…”

Section: Withania Somnifera: Therapeutically Potential Activitiesmentioning

confidence: 99%

Phyto‐therapeutic potential of Withania somnifera: Molecular mechanism and health implications

Yadav,

Tripathi,

Sangwan

2024

Phytotherapy Research

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Withania somnifera, the plant named Indian ginseng, Ashwagandha, or winter cherry, has been used since ancient times to cure various health ailments. Withania somnifera is rich in constituents belonging to chemical classes like alkaloids, saponins, flavonoids, phenolic acids, and withanolides. Several chemotypes were identified based on their phytochemical composition and credited for their multiple bioactivities. Besides, exhibiting neuroprotective, immunomodulatory, adaptogenic, anti‐stress, bone health, plant has shown promising anti‐cancer properties. Several withanolides have been reported to play a crucial role in cancer; they target cancer cells by different mechanisms such as modulating the expression of tumor suppressor genes, apoptosis, telomerase expression, and regulating cell signaling pathway. Though, many treatments are available for cancer; however, to date, no assured reliable cure for cancer is made available. Additionally, synthetic drugs may lead to development of resistance in time; therefore, focus on new and natural drugs for cancer therapeutics may prove a longtime effective alternative. This current report is a comprehensive combined analysis upto 2023 with articles focused on bio‐activities of plant Withania somnifera from various sources, including national and international government sources. This review focuses on understanding of various mechanisms and pathways to inhibit uncontrolled cell growth by W. somnifera bioactives, as reported in literature. This review provides a recent updated status of the W. somnifera on pharmacological properties in general and anti‐cancer in particular and may provide a guiding resource for researchers associated with natural product‐based cancer research and healthcare management.

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Section: Withania Somnifera: Therapeutically Potential Activitiesmentioning

confidence: 99%

Phyto‐therapeutic potential of Withania somnifera: Molecular mechanism and health implications

Yadav,

Tripathi,

Sangwan

2024

Phytotherapy Research

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“…U87, U251, GL26 Akt, mTOR, p70S6K, AMPKα, tuberin [10] MCF7, SUM159, SK-BR-3 WA binds to Cys303 of β-tubulin, αand β-tubulin [11] MDA-MB-231, MCF7 FOXO3a, Bim [12] MDA-MB-231, MCF7 Complex III, Bax, Bak [13] MDA-MB-231, MCF7 Cdk1, Cdc25B/C [14] MDA-MB-231, MCF7 STAT3 [15] MDA-MB-231, MCF7 Proteasome, autophagy [16] MDA-MB-231, MCF7, T-47D ER-α, p53 [17] MDA-MB-231, MCF7, T-47D, MDA-MB-68 p90-ribosomal S6 kinase, extracellular signal-regulated kinase 1/2 [18] MDA-MB-231, MCF7, T-47D, MDA-MB-468 Autophagy [19] HCT116 STAT3 [20] HCT-116, SW-480, SW-620 pS6K, p4E-BP1, Notch signaling [21] HCT116, SW480 Mad2, Cdc20 [22] MDA-1986, JMAR, UM-SCC-2, JHU011 Cell cycle alteration [23] HepG2, SNU449 Keap1, Nrf2 [24] H358, H460 ROS [25] H358, H460 Oxidative stress, lipid peroxidation, increased GSSG/GSH [26] A549 CAMs, Akt, NF-kB [27] A549 PI3K/Akt pathway [28] U-937 MMP, MAPK pathway [29] MDS92, MDS-L, HL-60, THP-1, Jurkat, Ramos HMOX1, LC3A/B [30] MOLT-4, Jurkat, REH, K-562, HeLa, Saos-2, SP2/0 p38-MAPK signaling, ATF-2, HSP27 [31] LY-10, LY-3, SudHL-6, Ramos, Raji, Mino, Jeko Hsp90, NF-kB [32] HSC3, U-2 OS mortalin-p53 interaction [33] PC-3, DU-145, LNCaP c-Fos, HSPA6, Hsp70, c-FLIP(L) [34] Caki STAT3 [35] Caki ROS, Bcl-2, Akt [4] M14, Mel501, SK28, Lu1205 Bcl-2, Bax [36] Tripterygium wilfordii Hook F is a perennial vine that grows in southeast and southern China. The plant has been used widely in traditional Chinese medicine and is also known as "Thunder of God vine" or "Seven-step vine" [37,38].…”

Section: Introductionmentioning

confidence: 99%

“…[ 1 , 2 ]). These studies have identified a large number of proteins and pathways, listed in Table 1 ([ 4 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]; adapted from ref. [ 1 ]), that are affected by WA in different cell types.…”

Section: Introductionmentioning

confidence: 99%

Withaferin A and Celastrol Overwhelm Proteostasis

Vilaboa,

Voellmy

2023

IJMS

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Withaferin A (WA) and celastrol (CEL) are major bioactive components of plants that have been widely employed in traditional medicine. The pleiotropic activities of plant preparations and the isolated compounds in vitro and in vivo have been documented in hundreds of studies. Both WA and CEL were shown to have anticancer activity. Although WA and CEL belong to different chemical classes, our synthesis of the available information suggests that the compounds share basic mechanisms of action. Both WA and CEL bind covalently to numerous proteins, causing the partial unfolding of some of these proteins and of many bystander proteins. The resulting proteotoxic stress, when excessive, leads to cell death. Both WA and CEL trigger the activation of the unfolded protein response (UPR) which, if the proteotoxic stress persists, results in apoptosis mediated by the PERK/eIF-2/ATF4/CHOP pathway or another UPR-dependent pathway. Other mechanisms of cell death may play contributory or even dominant roles depending on cell type. As shown in a proteomic study with WA, the compounds appear to function largely as electrophilic reactants, indiscriminately modifying reachable nucleophilic amino acid side chains of proteins. However, a remarkable degree of target specificity is imparted by the cellular context.

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Natural Coumarin Derivatives Targeting Melanoma

Silva

Nunes

Zhan

et al. 2024

CMC

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In general, a cancerous process starts from uncontrolled cell growth, apoptosis, and rapid proliferation of cellular clones, as well as, reactive oxygen species (ROS) and imbalance of ROS-antioxidant production also could be involved in the genesis of the disease. Cancer has accounted for millions of deaths worldwide every year, representing a relevant threat to human lives. In this context, malignant melanoma represents the most aggressive and deadliest type of cancer, leading to increased rates of patient deaths. Natural active compounds have demonstrated their pharmacological benefits in several different studies. Among these compounds, coumarin analogs have demonstrated promising biological profiles, considering their efficacy and low toxicity. In this context, this phytochemical oxygenated core has been broadly investigated since it presents several biological properties of interest in the medicinal field. Herein, we reported a complete compilation of studies focused on natural coumarins against melanoma, as well as, tyrosinase since it is a cooper-catalyzed oxidase that performs an essential role during melanogenesis (Eu-melanins and Pheo-melanins), which is associated with melanoma. Thus, three different subclasses of natural coumarin were described in detail, such as simple coumarin core, furanocoumarins, pyranocoumarins, and pyrone-substituents. Additionally, insights on tyrosinase have been provided, allowing an overview of some structural/functional aspects of its enzyme, such as the presence of a binuclear type 3 cooper coordination at the binding site of this target, acting as cofactors. Posteriorly, several coumarin-based analogs with anti-tyrosinase activity also were reported and discussed. Finally, we believe that unprecedented review can be a valuable source of information, which can be used to design and develop novel coumarin-based analogs targeting melanoma and also tyrosinase enzyme, contributing to the advances in the field of natural products.

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Comparative computational and experimental analyses of some natural small molecules to restore transcriptional activation function of p53 in cancer cells harbouring wild type and p53Ser46 mutant

Cited by 4 publications

References 56 publications

Phyto‐therapeutic potential of Withania somnifera: Molecular mechanism and health implications

Phyto‐therapeutic potential of Withania somnifera: Molecular mechanism and health implications

Withaferin A and Celastrol Overwhelm Proteostasis

Natural Coumarin Derivatives Targeting Melanoma

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