Curcuminoid Analogs Differentially Modulate Nuclear Factor Kappa-Light-Chain-Enhancer, P65 Serine276, Mitogen- and Stress-activated Protein Kinase 1 And MicroRNA 148a Status

Cavaleri, Franco

doi:10.1097/pp9.0000000000000024

Cited by 3 publications

(5 citation statements)

References 55 publications

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“…Most of these phytochemicals are ultimately natural pest control designed to regulate transcriptional events in grazers at multiple pathway nodes as defensive strategies. 66 - 68 Could a plant generate metabolites of these chemicals that serve as escalations of protective pharmacology over thousands of years as a natural survival mechanism—natural selection? Many of the ancient regulatory pathways like the NF-kappa-B Signaling, MAPK Signaling, and Nrf2 Signaling are highly conserved and still managing key cellular processes in a wide range of developed species.…”

Section: Discussionmentioning

confidence: 99%

Study of Drug Targets Associated With Oncogenesis and Cancer Cell Survival and the Therapeutic Activity of Engineered Ashwagandha Extract Having Differential Withanolide Constitutions

Cavaleri,

Chattopadhyay,

Palsule

et al. 2024

Integr Cancer Ther

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Ashwagandha ( Withania somnifera) has gained worldwide popularity for a multitude of health benefits inclusive of cancer-preventive and curative effects. Despite numerous research data supporting the benefits of this wonder herb, the actual use of ashwagandha for cancer treatment in clinics is limited. The primary reason for this is the inconsistent therapeutic outcome due to highly variable composition and constitution of active ingredients in the plant extract impacting ashwagandha’s pharmacology. We investigate here an engineered yield: an ashwagandha extract (Oncowithanib) that has a unique and fixed portion of active ingredients to achieve consistent and effective therapeutic activity. Using the MCF7 cell line, Oncowithanib was studied for its anti-neoplastic efficacy and drug targets associated with cell cycle regulation, translation machinery, and cell survival and apoptosis. Results demonstrate a dose-dependent decline in Oncowithanib-treated MCF7 cell viability and reduced colony-forming ability. Treated cells showed increased cell death as evidenced by enhancement of Caspase 3 enzyme activity and decreased expressions of cell proliferation markers such as Ki67 and Aurora Kinase A. Oncowithanib treatment was also found to be associated with expressional suppression of key cellular kinases such as RSK1, Akt1, and mTOR in MCF7 cells. Our findings indicate that Oncowithanib decreases MCF7 cell survival and propagation, and sheds light on common drug targets that might be good candidates for the development of cancer therapeutics. Further in-depth investigations are required to fully explore the potency and pharmacology of this novel extract. This study also highlights the importance of the standardization of herbal extracts to get consistent therapeutic activity for the disease indication.

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Section: Discussionmentioning

confidence: 99%

Study of Drug Targets Associated With Oncogenesis and Cancer Cell Survival and the Therapeutic Activity of Engineered Ashwagandha Extract Having Differential Withanolide Constitutions

Cavaleri,

Chattopadhyay,

Palsule

et al. 2024

Integr Cancer Ther

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“…After overnight incubation at 4 °C, membranes were probed with goat anti-rabbit secondary antibody (1 :10,000) (Sigma, USA) for 1 h at room temperature and were developed with the chemiluminescent agent western HRP substrate (Millipore, Sigma). Membranes were imaged using Fluor-S ™ MAX MultiImager (Bio-Rad) and quantifed using Quantity One R software [24,35].…”

Section: Hfdpc Clonogenic Activity Assaymentioning

confidence: 99%

“…Nevertheless, because these extracts are ultimately concoctions of multiple bioactive phytochemicals even if the extract is purified, predictability and repeatability can be a problem. An extract of curcumin that is 97% pure curcumin, for instance, will consist of three curcuminoids of homologous structure, nevertheless, bearing differential molecular features that also afford differential pharmacology [ 24 ]. Therefore, if proportions of these actives change the pharmacology changes, the proportions of these constituents will be different from extraction batch to batch based on climate changes, soil type, and agricultural practices that differ in one country or territory over another [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Study of Drug Target Identification and Associated Molecular Mechanisms for the Therapeutic Activity and Hair Follicle Induction of Two Ashwagandha Extracts Having Differential Withanolide Constitutions

Cavaleri,

Chattopadhyay,

Palsule

et al. 2023

Journal of Nutrition and Metabolism

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Background. Ashwagandha extracts play a significant role in traditional Indian medicine to help treat a wide range of disorders from amnesia, erectile dysfunction, neurodegenerative and cardiovascular diseases, cancer, stress, anxiety, and many more. Ashwagandha root is enriched with bioactive plant metabolites of which withanolides are the most important ones. The concentration and constitution of withanolides primarily determine ashwagandha’s potency and pharmacology. Various factors modulate the withanolide constitution in the plant-derived extracts, rendering inconsistent therapeutic efficacy. Standardisation of the extraction protocol and a better understanding of the pharmacology mechanism of different extracts with varied withanolide constitutions is therefore critical for developing reliable, repeatable, and effective ashwagandha-based treatment. Objectives. Here, we work toward defining indication mechanisms for two varieties of ashwagandha extract—ASHWITH (ASH-Ext1) and Regenolide (ASH-Ext2)—with different proprietary withanolide proportions. Methods. ASH-Ext1 was studied for antioxidant signaling modulation using HEK293, HeLa, and A549 cells, and ASH-Ext2 was studied for subcellular drug targets associated with the reactivation and longevity of human hair follicles, using primary human hair follicle dermal papilla cells (HFDPCs). Results. Study findings support the antioxidant activity and Nrf2 signaling modulation by ASH-Ext1 in various cell models. Of note, ASH-Ext2 was found to increase β-catenin and telomerase reverse transcriptase (TERT) protein expression levels in HFDPCs. Conclusion. The results of drug target modulation show us that the withanolide constitution associated with different extraction protocols influences the pharmacological potential of the extract significantly and points to the value of standardisation not only of total withanolide content but also of internal withanolide proportions.

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“…Thus, the role of miR-148a varies in the progression of different kinds of cancers. Interestingly, just like its role in different kinds of cancer progression, miR-148a expression is differently regulated by various curcuminoids [ 48 ]. More specifically, curcumin I (diferuloylmethane) does not affect the miR-148a expression, while curcumin II (desmethoxycurcumin) downregulates, while curcumin III (bisdemethoxycurcumin) upregulates the miR-148a expression [ 48 ].…”

Section: Mirnas and Androgen Signalingmentioning

confidence: 99%

“…Interestingly, just like its role in different kinds of cancer progression, miR-148a expression is differently regulated by various curcuminoids [ 48 ]. More specifically, curcumin I (diferuloylmethane) does not affect the miR-148a expression, while curcumin II (desmethoxycurcumin) downregulates, while curcumin III (bisdemethoxycurcumin) upregulates the miR-148a expression [ 48 ]. Similarly, another study has unraveled the role of several miRNAs, including miR-19a, miR-27a, and miR-133b, in PC progression in LNCaP cells in response to androgen.…”

Section: Mirnas and Androgen Signalingmentioning

confidence: 99%

Targeting androgen receptor signaling with MicroRNAs and Curcumin: a promising therapeutic approach for Prostate Cancer Prevention and intervention

et al. 2021

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Prostate cancer (PC) is a multifactorial disease characterized by the abrogation of androgen receptor signaling. Advancement in microbiology techniques has highlighted the significant role of microRNAs (miRNAs) in the progression of PC cells from an androgen-dependent to an androgen-independent state. At that stage, prostate tumors also fail to respond to currently practiced hormone therapies. So, studies in recent decades are focused on investigating the anti-tumor effects of natural compounds in PC. Curcumin is widely recognized and now of huge prestige for its anti-proliferative abilities in different types of cancer. However, its limited solubility, compatibility, and instability in the aqueous phase are major hurdles when administering. Nanoformulations have proven to be an excellent drug delivery system for various drugs and can be used as potential delivery platforms for curcumin in PC. In this review, a shed light is given on the miRNAs-mediated regulation of androgen receptor (AR) signaling and miRNA-curcumin interplay in PC, as well as on curcumin-based nanoformulations that can be used as possible therapeutic solutions for PC.

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Curcuminoid Analogs Differentially Modulate Nuclear Factor Kappa-Light-Chain-Enhancer, P65 Serine276, Mitogen- and Stress-activated Protein Kinase 1 And MicroRNA 148a Status

Cited by 3 publications

References 55 publications

Study of Drug Targets Associated With Oncogenesis and Cancer Cell Survival and the Therapeutic Activity of Engineered Ashwagandha Extract Having Differential Withanolide Constitutions

Study of Drug Targets Associated With Oncogenesis and Cancer Cell Survival and the Therapeutic Activity of Engineered Ashwagandha Extract Having Differential Withanolide Constitutions

Study of Drug Target Identification and Associated Molecular Mechanisms for the Therapeutic Activity and Hair Follicle Induction of Two Ashwagandha Extracts Having Differential Withanolide Constitutions

Targeting androgen receptor signaling with MicroRNAs and Curcumin: a promising therapeutic approach for Prostate Cancer Prevention and intervention

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