Cytotoxicity of Tanshinone IIA combined with Taxol on drug‐resist breast cancer cells MCF‐7 through inhibition of Tau

Lin, Hui; Zheng, Luya; Xie, Bin; Cui, Binbin; Xia, Aixiao; Zx, Lin; Zhou, Peng

doi:10.1002/ptr.6014

Cited by 23 publications

(18 citation statements)

References 32 publications

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“…Tanshinone IIA (Tan IIA), an effective active ingredient of Salvia miltiorrhiza, is often used clinically for the treatment of ischemic heart disease because of its pharmacological actions such as improving coronary circulation (Jiang et al, ), lowering blood lipids (Kang et al, ), inhibiting platelet aggregation and thrombus formation (Li, Yang, & Zhao, ), retarding development of arteriosclerosis (Adams, Wang, Yang, & Lien, ), decreasing inflammatory reaction (Fan et al, ), and etc. In addition, many studies have shown that Tan IIA has antitumor effects and can kill a variety of cancer cells, including breast cancer cells (Lin et al, ), gastric cancer cells (Chen, Shi, Liu, & Zhong, ), colon cancer cells (Liu et al, ), prostate cancer cells (Won et al, ), and etc. Because one of the main toxic side effects of Dox is cardiotoxicity, and TanIIA not only has antitumor activity but also cardiovascular protective effect, therefore, we combined Dox with Tan IIA to assess the effect of Tan IIA on the toxic side effects of Dox while evaluating its effect on the anti‐breast cancer activity of Dox and to investigate the possible mechanism of the effect of Tan IIA on the anti‐breast cancer activity of Dox.…”

Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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Combination of tanshinone IIA and doxorubicin possesses synergism and attenuation effects on doxorubicin in the treatment of breast cancer

Li¹,

Liu

Zhao³

et al. 2019

Phytotherapy Research

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Doxorubicin (Dox) is a first‐line drug for breast cancer chemotherapy. However, with the prolongation of chemotherapy cycle, breast cancer cells are increasingly tempt to resist Dox, and meanwhile, high cumulative dose of Dox brings enhancing toxic side effects, and these effects may lead to chemotherapy failure. Hence, it is necessary to search an agent in combination medication with Dox, which can not only enhance the chemosensitivity of Dox but also reduce the toxic side effects. Tanshinone IIA (Tan IIA) is reported to have antitumor activity in addition to its cardiovascular protective effects. We employed human breast cancer MCF‐7 and MCF‐7/dox cells in order to assess whether Tan IIA might perform such function. Our in vitro studies showed that Tan IIA could enhance the sensitivity of breast cancer cells to Dox through inhibiting the PTEN/AKT pathway and downregulating the expression of efflux ABC transporters including P‐gp, BCRP, and MRP1. In addition, our in vivo studies showed Tan IIA enhanced the chemotherapeutic effect of Dox against breast cancer while reducing its toxic side effects including weight loss, myelosuppression, cardiotoxicity, and nephrotoxicity. Therefore, Tan IIA could be used as a novel agent combined with Dox in breast cancer therapy.

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Combination of tanshinone IIA and doxorubicin possesses synergism and attenuation effects on doxorubicin in the treatment of breast cancer

Li¹,

Liu

Zhao³

et al. 2019

Phytotherapy Research

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“…For example, Tau was shown to regulate the MT-dependent migration of cancer cells (Breuzard et al, 2019). Finally, similar to stathmin, Tau level of expression modulates clinical MT-targeting agent efficiencies, such as taxanes or vinca alkaloids (Rouzier et al, 2005; Li et al, 2013; Smoter et al, 2013; Malesinski et al, 2015; Lin et al, 2018).…”

Section: Perspectivesmentioning

confidence: 99%

Role of Tau as a Microtubule-Associated Protein: Structural and Functional Aspects

Barbier

Zejneli

Martinho

et al. 2019

Front. Aging Neurosci.

385

248

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Microtubules (MTs) play a fundamental role in many vital processes such as cell division and neuronal activity. They are key structural and functional elements in axons, supporting neurite differentiation and growth, as well as transporting motor proteins along the axons, which use MTs as support tracks. Tau is a stabilizing MT associated protein, whose functions are mainly regulated by phosphorylation. A disruption of the MT network, which might be caused by Tau loss of function, is observed in a group of related diseases called tauopathies, which includes Alzheimer’s disease (AD). Tau is found hyperphosphorylated in AD, which might account for its loss of MT stabilizing capacity. Since destabilization of MTs after dissociation of Tau could contribute to toxicity in neurodegenerative diseases, a molecular understanding of this interaction and its regulation is essential.

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“…Clinically, the patients with PTX chemoresistance show over expression of MAPT significantly [24]. Identification of MAPT inhibitors and their use in cancer treatment along with PTX improve the treatment results in the either case, PTX sensitive and resistant tumor [25,26].…”

Section: Introductionmentioning

confidence: 99%

Virtual screening of MAP-Tauprotein inhibitors fromSemecarpus anacardiumLinn. leaf extract for cancer prevention

Singh

Ranjan

Tripathi

et al. 2020

Preprint

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Semecarpus anacardium is a well known Indian medicinal plant with various medicinalproperties like hypoglycemic, antioxidant, anticancer, anti-inflammatory, anti-geriatric, antimicrobial and hair growth promoter, etc. The molecular mechanism of metabolites from fruiting bodies of S. anacardium against cancer has been described but anticancerous properties in its leaves are still unknown. The leaves were extracted in petroleum ether, ethyl acetate and methanol and assayed for anticancer activity using MTT assay. The active extract was evaluated for mode of cell death induction using EtBr-AO double staining and analyzed for phytochemical constituents using GC-MS, followed by molecular docking studies for exploration of possibility for anticancer agents and Drugability. In this study, ethyl acetate extract of leaf was found potent cytotoxic in MCF-7 cells and also induced apoptosis. It has also found the SLE is safe for normal cells. The molecular docking studies were done to explore the probable mechanism of action of the extract which showed 9 compounds are targeting the microtubule-associated protein tau (MAPT). MAPT promotes assembling and prevents disassembling to arrest the cell cycle. The overexpression of MAPT induces chemoresistance to cancerous cells against conventional drugs like paclitaxel. We have identified 17 compounds from ethyl acetate extract of S. anacardium leaves and drawn its chemical structure by using chembiodraw software to transform into pdb format. Further, the compounds have been subjected for molecular docking study to investigate its interactive efficiency with MAPT protein. The compound 13 had higher interactive potential to MAPT with binding energy -31.75 kcal/mol and lowest binding energy (-15.44 kcal/mol) was observed in compound 6. The present study suggested that the compounds from leaves of S. anacardium could be alternative approach of conventional drug for cancer treatment with cost effective and less side effect.

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Cytotoxicity of Tanshinone IIA combined with Taxol on drug‐resist breast cancer cells MCF‐7 through inhibition of Tau

Cited by 23 publications

References 32 publications

Combination of tanshinone IIA and doxorubicin possesses synergism and attenuation effects on doxorubicin in the treatment of breast cancer

Combination of tanshinone IIA and doxorubicin possesses synergism and attenuation effects on doxorubicin in the treatment of breast cancer

Role of Tau as a Microtubule-Associated Protein: Structural and Functional Aspects

Virtual screening of MAP-Tauprotein inhibitors fromSemecarpus anacardiumLinn. leaf extract for cancer prevention

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