Pharmacological attenuation of melanoma by tryptanthrin pertains to the suppression of MITF-M through MEK/ERK signaling axis

Shabna, Anwar; Antony, Jayesh; Vijayakurup, Vinod; Saikia, Minakshi; Liju, Vijayasteltar Belsamma; Retnakumari, Archana; Amrutha, Nisthul A; Alex, Vijai V; Swetha, Mundanattu; Aiswarya, Sreekumar U.; Jannet, Somaraj; Unni, Uma S.; Sundaram, Sankar; Sherin, D.R.; Anto, Nikhil Ponnoor; Bava, Smitha V.; Sadasivan, C.; Ran, Sophia; Anto, Ruby John

doi:10.1007/s00018-022-04476-y

Cited by 7 publications

(5 citation statements)

References 43 publications

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“…3 TRYP regulated inflammation by modulating the TLR4-MyD88 pathway. 53 Our results indicated that TRYP pretreatment could reduce the expression of TLR4 and MyD88 and inhibit the phosphorylation of IκBα, thereby suppressing the activation of NF-κB p65 into the nucleus. The results of the IF experiments confirmed this.…”

Section: Discussionmentioning

confidence: 99%

“…When TLR4 binds to its corresponding ligand, MyD88 attracts IRAK-4 to the TLRs, activating the IKK complex, which then activates NF-κB . TRYP regulated inflammation by modulating the TLR4-MyD88 pathway . Our results indicated that TRYP pretreatment could reduce the expression of TLR4 and MyD88 and inhibit the phosphorylation of IκBα, thereby suppressing the activation of NF-κB p65 into the nucleus.…”

Section: Discussionmentioning

confidence: 99%

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Exploring the Anti-Inflammatory Effect of Tryptanthrin by Regulating TLR4/MyD88/ROS/NF-κB, JAK/STAT3, and Keap1/Nrf2 Signaling Pathways

Zhu,

Cheng,

et al. 2024

ACS Omega

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Tryptanthrin (TRYP) is the main active ingredient in Indigo Naturalis. Studies have shown that TRYP had excellent anti-inflammatory activity, but its specific mechanism has been unclear. In this work, the differentially expressed proteins resulting from TRYP intervention in LPS-stimulated RAW264.7 cells were obtained based on tandem mass tag proteomics technology. The anti-inflammatory mechanism of TRYP was further validated by a combination of experiments using the LPS-induced RAW264.7 cell model in vitro and the DSS-induced UC mouse model (free drinking 2.5% DSS) in vivo. The results demonstrated that TRYP could inhibit levels of NO, IL-6, and TNF-α in LPS-induced RAW264.7 cells. Twelve differential proteins were screened out. And the results indicated that TRYP could inhibit upregulated levels of gp91phox, p22phox, FcεRIγ, IKKα/β, and p-IκBα and reduce ROS levels in vitro. Besides, after TRYP treatment, the health conditions of colitis mice were all improved. Furthermore, TRYP inhibited the activation of JAK/STAT3, nuclear translocation of NF-κB p65, and promoted the nuclear expression of Nrf2 in vitro and in vivo. This work preliminarily indicated that TRYP might suppress the TLR4/MyD88/ROS/NF-κB and JAK/STAT3 signaling pathways to exert anti-inflammatory effects. Additionally, TRYP could achieve antioxidant effects by regulating the Keap1/ Nrf2 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Exploring the Anti-Inflammatory Effect of Tryptanthrin by Regulating TLR4/MyD88/ROS/NF-κB, JAK/STAT3, and Keap1/Nrf2 Signaling Pathways

Zhu,

Cheng,

et al. 2024

ACS Omega

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“…Since many of the currently available chemotherapeutic agents are phytochemicals, plants can be a potential source for exploring new drugs. Being a group bioprospecting for anticancer natural products, we have reported some potent anticancer molecules [23], [24]. We had previously reported a very effective chemotherapeutic combinatorial regimen of paclitaxel and the phytochemical, curcumin, with remarkably lesser cost as well as side effects, for the treatment of cervical cancer [18,25,26].…”

Section: Discussionmentioning

confidence: 99%

Kaempferide induces apoptosis in cervical cancer by attenuating the HPV oncoproteins, E6 and E7

Nath

Alex

Aiswarya

et al. 2023

Preprint

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Despite the advancement in HPV prevention strategies, cervical cancer is a leading cause of cancer death in women worldwide. The anticancer potential of kaempferide, which was derived from Chromolaena odorata, was previously revealed in our in-vitro study. The current investigation aims to confirm the therapeutic efficacy of the molecule against cervical cancer, in-vitro and in-vivo. In NOD-SCID mice with HeLa Luc+ xenografts, kaempferide significantly increases ROS production resulting in a drastic decrease in the luc activity and growth of cervical tumours. It also exhibits down-regulation of oncoproteins E6, E7 and MDM2 and concurrent up-regulation of p53, p21 and pRb. The degradation of phospho-pRb, along with a strong expression of cleaved PARP, TUNEL positivity and a significant decrease in PCNA expression, confirms apoptotic mode of cell death in the treated tissues. Taken together, our study reveals the antioncogenic potential of kaempferide, which regulates oncoproteins and tumor suppressors accordingly. This is the first report depicting kaempferide as an inhibitor of HPV oncoproteins and hence as a candidate drug molecule against cervical cancer.

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“…11 Subsequently, the study on tryptanthrin alkaloid was discussed in another review article in 2013, where various synthetic methods were applied for the preparation of tryptanthrin. 12a Owing to its pharmacologically aromatic indoloquinazoline moiety with a wide range of biological and pharmacological activities, tryptanthrin has been extensively applied as a parental backbone via the modification of different functional groups for the development of new tryptanthrin derivatives with significant medicinal benefits as antitrypanosomal, 13 antifungal, 14,15 anti-phytopathogenic bacterial, 16 antibacterial, [17][18][19][20][21] anti-MRSA, 22 antiviral, [23][24][25][26] antiangiogenic, 27 anti-inflammatory, [28][29][30][31][32][33][34][35][36][37][38][39] anti-leishmanial, 40,41 antimalarial, 42 antiplasmodial, 43 antiparasitic, 44 antitubercular, [45][46][47] and anti-cancer [48][49][50][51][52][53][54]…”

Section: Introductionmentioning

confidence: 99%

Recent advances of tryptanthrin and its derivatives as potential anticancer agents

Zhou

2024

RSC Med. Chem.

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Pharmacological attenuation of melanoma by tryptanthrin pertains to the suppression of MITF-M through MEK/ERK signaling axis

Cited by 7 publications

References 43 publications

Exploring the Anti-Inflammatory Effect of Tryptanthrin by Regulating TLR4/MyD88/ROS/NF-κB, JAK/STAT3, and Keap1/Nrf2 Signaling Pathways

Exploring the Anti-Inflammatory Effect of Tryptanthrin by Regulating TLR4/MyD88/ROS/NF-κB, JAK/STAT3, and Keap1/Nrf2 Signaling Pathways

Kaempferide induces apoptosis in cervical cancer by attenuating the HPV oncoproteins, E6 and E7

Recent advances of tryptanthrin and its derivatives as potential anticancer agents

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