A new pyrrole based small molecule from Tinospora cordifolia induces apoptosis in MDA-MB-231 breast cancer cells via ROS mediated mitochondrial damage and restoration of p53 activity

Rashmi, Kothary; Raj, M. Harsha; Paul, Manoj; Girish, K. S.; Salimath, Bharathi P.; Aparna, H. S.

doi:10.1016/j.cbi.2018.12.005

Cited by 33 publications

(28 citation statements)

References 39 publications

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“…Finally, we analyzed the effect of P 4 on the activation of NFAT1, an important calcium-dependent and pro-proliferative transcription factor that acts as checkpoints in the cell cycle [ 49 , 50 , 51 , 52 , 53 ].…”

Section: Resultsmentioning

confidence: 99%

PGRMC1 Inhibits Progesterone-Evoked Proliferation and Ca2+ Entry Via STIM2 in MDA-MB-231 Cells

Cantonero

Salido

Rosado

et al. 2020

IJMS

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Progesterone receptor membrane component 1 (PGRMC1) has been shown to regulate some cancer hallmarks. Progesterone (P4) evokes intracellular calcium (Ca2+) changes in the triple-negative breast cancer cell lines (MDA-MB-231, MDA-MB-468, and BT-20) and in other breast cancer cell lines like the luminal MCF7 cells. PGRMC1 expression is elevated in MDA-MB-231 and MCF7 cells as compared to non-tumoral MCF10A cell line, and PGRMC1 silencing enhances P4-evoked Ca2+ mobilization. Here, we found a new P4-dependent Ca2+ mobilization pathway in MDA-MB-231 cells and other triple-negative breast cancer cells, as well as in MCF7 cells that involved Stromal interaction molecule 2 (STIM2), Calcium release-activated calcium channel protein 1 (Orai1), and Transient Receptor Potential Channel 1 (TRPC1). Stromal interaction molecule 1 (STIM1) was not involved in this novel Ca2+ pathway, as evidenced by using siRNA STIM1. PGRMC1 silencing reduced the negative effect of P4 on cell proliferation and cell death in MDA-MB-231 cells. In line with the latter observation, Nuclear Factor of Activated T-Cells 1 (NFAT1) nuclear accumulation due to P4 incubation for 48 h was enhanced in cells transfected with the small hairpin siRNA against PGRMC1 (shPGRMC1). These results provide evidence for a novel P4-evoked Ca2+ entry pathway that is downregulated by PGRMC1.

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Section: Resultsmentioning

confidence: 99%

PGRMC1 Inhibits Progesterone-Evoked Proliferation and Ca2+ Entry Via STIM2 in MDA-MB-231 Cells

Cantonero

Salido

Rosado

et al. 2020

IJMS

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“…Flavanoids have a chemopreventive role in cancer. Pyrrole-based molecules induced apoptosis and cytotoxic effects [13]. Palmatine showed enhanced antioxidant activity by the increase in the level of antioxidant enzymes and also showed inhibition of lipid peroxidation showing role in detoxification pathway [20].…”

Section: Phytocomponents and Its Mechanism Of Action Against Cancer Cmentioning

confidence: 99%

“…Rashmi KC et al used Tc leaves, due to the presence of bis(2-ethylhexyl)-1H-pyrrole-3,4-dicarboxylate. Some studies have even used the whole plant [13].…”

Section: Parts Of the Tc With Anti-carcinogenic Effectmentioning

confidence: 99%

“…The various phytocomponents identified from the studies analyzed in the systematic review included berberine, new clerodane furanodiptherineglycosidae, elligic acid, kaempferol, N-formylannonain, magnoflorine, jatrorrhizine palmatine, 11-hydroxymustakone, cordifolioside A, tinocordiside, yangambin, anthraquinones, terpenoids, saponins and phenol, pyrrole-based small molecules, quercetin and rutin, arabinogalectian, palmatine, clerodane-derived diterpenoids and hexane fractions. These phytocomponents induced anticancer effect via mitochondrial-mediated apoptosis, cytotoxic activity, mutagenic activity, reduction in tumor size, triggering reactive oxygen species, decreased gene expression of the cell cycle, effectively inhibiting cancer proliferation [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. The mechanism of action of Tc depends on the phytocomponents used.…”

Section: Phytocomponents and Its Mechanism Of Action Against Cancer Cmentioning

confidence: 99%

“…They found phytocomponents of Tc extract having anticancer activity and also observed inhibition of tumor proliferation. Despite promising results, the major limitation of most of the abovementioned studies is that several key aspects, including the complete mechanism of action, signaling, and pharmacological actions were nor clearly delineated [13]. Quercetin and rutin belong to phenolic phytocomponents extracted from Tc showed antiproliferative activity and was confirmed on human breast cancer MDA-MB-231 cells through induction of apoptosis, expression of altered genes and checking for the levels of intracellular ROS.…”

Section: Anti-carcinogenic Effect Of Tc Phytocomponentsmentioning

confidence: 99%

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Effect of Tinospora cordifolia-Derived Phytocomponents on Cancer: A Systematic Review

et al. 2019

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The major cancer therapeutic modalities include surgery, chemotherapy and radiotherapy. Although these treatment regimens have played a significant role in effectively inhibiting cancer, their associated morbidity reduces the overall quality of life. Thus, researchers are striving to identify any alternate therapeutic approach capable of inhibiting cancer without eliciting the added morbidity. Among the alternate cancer therapeutics being researched, much importance is being given to the use of plants due to the presence of a wide variety of anti-carcinogenic compounds. Tinospora cordifolia (Tc) is one such plant and has shown to exhibit anti-carcinogenic properties. The present review aimed to systematically analyze published data on the effect of Tinospora cordifolia-derived phytocomponents on cancer. PubMed, Scopus, Web of Science, Embase and Cochrane library were searched using the keywords Tinospora cordifolia; anticancer; phytocomponents until March 20, 2019. In vivo and in vitro original studies in the English language were included. Of the 342 articles identified, only 25 articles met the selection criteria and were included in the review. Significant anti-carcinogenic properties were exhibited by Tinospora cordifolia-derived phytocompounds including palmative, berberine, new clerodane furanoditerene glycoside, arabinogalactan, phenolic compounds and epoxy cleodane diterpene. No significant side effects have been elicited with its use. Based on the data from the included studies, Tinospora cordifolia could be a natural therapeutic agent for cancer, provided its anti-carcinogenic properties can be elicited consistently at a large scale in clinical trials.

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Caspase‐driven cancer therapies: Navigating the bridge between lab discoveries and clinical applications

Allani,

Akhilesh,

Tiwari

2024

Cell Biochemistry & Function

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Apoptosis is the cell's natural intrinsic regulatory mechanism of normal cells for programmed cell death, which plays an important role in cancer as a classical mechanism of tumor cell death causing minimal inflammation without causing damage to other cells in the vicinity. Induction of apoptosis by activation of caspases is one of the primary targets for cancer treatment. Over the years, a diverse range of natural, synthetic, and semisynthetic compounds and their derivatives have been investigated for their caspase‐mediated apoptosis‐induced anticancer activities. The review aims to compile the preclinical evidence and highlight the critical mechanistic pathways related to caspase‐induced cell apoptosis in cancer treatment. The focus is placed on the key components of the mechanisms, including their chemical nature, and specific attention is given to phytochemicals derived from natural sources and synthetic and semisynthetic compounds. 180+ compounds from the past two decades with potential as anticancer agents are discussed in this review article. By summarizing the current knowledge and advancements in this field, this review provides a comprehensive overview of potential therapeutic strategies targeting apoptosis in cancer cells. The findings presented herein contribute to the ongoing efforts to combat cancer and stimulate further research into the development of effective and targeted anticancer therapies.

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A new pyrrole based small molecule from Tinospora cordifolia induces apoptosis in MDA-MB-231 breast cancer cells via ROS mediated mitochondrial damage and restoration of p53 activity

Cited by 33 publications

References 39 publications

PGRMC1 Inhibits Progesterone-Evoked Proliferation and Ca2+ Entry Via STIM2 in MDA-MB-231 Cells

PGRMC1 Inhibits Progesterone-Evoked Proliferation and Ca2+ Entry Via STIM2 in MDA-MB-231 Cells

Effect of Tinospora cordifolia-Derived Phytocomponents on Cancer: A Systematic Review

Caspase‐driven cancer therapies: Navigating the bridge between lab discoveries and clinical applications

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