Chemical Strategy to Translate Genetic/epigenetic Mechanisms to Breast Cancer Therapeutics

: Breast cancer is the most common type of malignancy among ladies (around 30% of newly diagnosed patients every year). To date, various modern treatment modalities for breast cancer, such as radiotherapy, surgical method, hormonal therapy, and chemotherapeutic drug utilisation, are available. However, adverse drug reactions, therapeutic resistance, metastasis, or cancer reoccurrence chances remain the primary causes of mortality for breast cancer patients. To overcome all the potential drawbacks, we need to investigate novel techniques and strategies previously not considered and treat breast cancer effectively with safety and efficacy. For centuries, we utilise phytochemicals to treat various diseases because of their safety, low-cost & least or no side effects. Recently, naturally produced phytochemicals gain immense attention as potential breast cancer therapeutics because of their ideal characteristics; for instance, they operate via modulating molecular pathways associated with cancer growth and progression. The primary mechanism involves inhibition of cell proliferation, angiogenesis, migration, invasion, increasing anti-oxidant status, initiation of the arrest of the cell cycle, and apoptosis. Remedial viability gets effectively enhanced when phytochemicals work as adjuvants with chemotherapeutic drugs. This comprehensive review revolves around the latest chemopreventive, chemotherapeutic, and chemoprotective treatments with their molecular mechanisms to treat breast cancer by utilising phytochemicals such as vinca alkaloids, resveratrol, curcumin, paclitaxel, silibinin, quercetin, genistein and epigallocatechin gallate. The authors wish to extend the field of phytochemical study for its scientific validity and its druggability.

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An Extract of Taro (Colocasia esculenta) Mediates Potent Inhibitory Actions on Metastatic and Cancer Stem Cells by Tumor Cell-Autonomous and Immune-Dependent Mechanisms

Breast Cancer Basic and Clinical Research ◽

10.1177/11782234211034937 ◽

2021 ◽

Vol 15 ◽

pp. 117822342110349

Author(s):

Namita Kundu ◽

Xinrong Ma ◽

Stephen Hoag ◽

Fang Wang ◽

Ahmed Ibrahim ◽

...

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Tumor Cell ◽

Cell Lines ◽

Nk Cell ◽

Cancer Therapeutics ◽

Colocasia Esculenta ◽

Biologically Active ◽

Tumor Cell Migration

The taro plant, Colocasia esculenta, contains bioactive proteins with potential as cancer therapeutics. Several groups have reported anti-cancer activity in vitro and in vivo of taro-derived extracts (TEs). We reported that TE inhibits metastasis in a syngeneic murine model of Triple-Negative Breast Cancer (TNBC). Purpose: We sought to confirm our earlier studies in additional models and to identify novel mechanisms by which efficacy is achieved. Methods: We employed a panel of murine and human breast and ovarian cancer cell lines to determine the effect of TE on tumor cell viability, migration, and the ability to support cancer stem cells. Two syngeneic models of TNBC were employed to confirm our earlier report that TE potently inhibits metastasis. Cancer stem cell assays were employed to determine the ability of TE to inhibit tumorsphere-forming ability and to inhibit aldehyde dehydrogenase activity. To determine if host immunity contributes to the mechanism of metastasis inhibition, efficacy was assessed in immune-compromised mice. Results: We demonstrate that viability of some, but not all cell lines is inhibited by TE. Likewise, tumor cell migration is inhibited by TE. Using 2 immune competent, syngeneic models of TNBC, we confirm our earlier findings that tumor metastasis is potently inhibited by TE. We also demonstrate, for the first time, that TE directly inhibits breast cancer stem cells. Administration of TE to mice elicits expansion of several spleen cell populations but it was not known if host immune cells contribute to the mechanism by which TE inhibits tumor cell dissemination. In novel findings, we now show that the ability of TE to inhibit metastasis relies on immune T-cell-dependent, but not B cell or Natural Killer (NK)-cell-dependent mechanisms. Thus, both tumor cell-autonomous and host immune factors contribute to the mechanisms underlying TE efficacy. Our long-term goal is to evaluate TE efficacy in clinical trials. Most of our past studies as well as many of the results reported in this report were carried out using an isolation protocol described earlier (TE). In preparation for a near future clinical trial, we have now developed a strategy to isolate an enriched taro fraction, TE-method 2, (TE-M2) as well as a more purified subfraction (TE-M2F1) which can be scaled up under Good Manufacturing Practice (GMP) conditions for evaluation in human subjects. We demonstrate that TE-M2 and TE-M2F1 retain the anti-metastatic properties of TE. Conclusions: These studies provide further support for the continued examination of biologically active components of Colocasia esculenta as potential new therapeutic entities and identify a method to isolate sufficient quantities under GMP conditions to conduct early phase clinical studies.

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The ligand (s) anchored lipobrid nanoconstruct mediated delivery of methotrexate: an effective approach in breast cancer therapeutics

Nanomedicine Nanotechnology Biology and Medicine ◽

10.1016/j.nano.2016.05.008 ◽

2016 ◽

Vol 12 (7) ◽

pp. 2043-2060 ◽

Cited By ~ 17

Author(s):

Neeraj K. Garg ◽

Bhupinder Singh ◽

Varun Kushwah ◽

Rajeev K. Tyagi ◽

Rajeev Sharma ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Therapeutics

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Boron clusters as breast cancer therapeutics

Journal of Inorganic Biochemistry ◽

10.1016/j.jinorgbio.2021.111412 ◽

2021 ◽

pp. 111412

Author(s):

N. Murphy ◽

E. McCarthy ◽

R. Dwyer ◽

P. Farràs

Keyword(s):

Breast Cancer ◽

Cancer Therapeutics ◽

Boron Clusters

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A chemical screen in diverse breast cancer cell lines reveals genetic enhancers and suppressors of sensitivity to PI3K isoform-selective inhibition

Biochemical Journal ◽

10.1042/bj20080639 ◽

2008 ◽

Vol 415 (1) ◽

pp. 97-110 ◽

Cited By ~ 98

Author(s):

Neil E. Torbett ◽

Antonio Luna-Moran ◽

Zachary A. Knight ◽

Andrew Houk ◽

Mark Moasser ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Cancer Therapeutics ◽

Cancer Cell Lines ◽

Genetic Alterations ◽

Breast Cancer Cell Lines ◽

Selective Inhibitors

The PI3K (phosphoinositide 3-kinase) pathway regulates cell proliferation, survival and migration and is consequently of great interest for targeted cancer therapy. Using a panel of small-molecule PI3K isoform-selective inhibitors in a diverse set of breast cancer cell lines, we have demonstrated that the biochemical and biological responses were highly variable and dependent on the genetic alterations present. p110α inhibitors were generally effective in inhibiting the phosphorylation of PKB (protein kinase B)/Akt and S6, two downstream components of PI3K signalling, in most cell lines examined. In contrast, p110β-selective inhibitors only reduced PKB/Akt phosphorylation in PTEN (phosphatase and tensin homologue deleted on chromosome 10) mutant cell lines, and was associated with a lesser decrease in S6 phosphorylation. PI3K inhibitors reduced cell viability by causing cell-cycle arrest in the G1 phase, with multi-targeted inhibitors causing the most potent effects. Cells expressing mutant Ras were resistant to the cell-cycle effects of PI3K inhibition, which could be reversed using inhibitors of Ras signalling pathways. Taken together, our data indicate that these compounds, alone or in suitable combinations, may be useful as breast cancer therapeutics, when used in appropriate genetic contexts.

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