Efficacy and safety of curcumin in combination with paclitaxel in patients with advanced, metastatic breast cancer: A comparative, randomized, double-blind, placebo-controlled clinical trial

Saghatelyan, Tatul; Tananyan, Armen; Janoyan, Naira; Tadevosyan, A.H.; Petrosyan, Hasmik; Hovhannisyan, Araxia; Hayrapetyan, Lidia; Arustamyan, Mikael; Arnhold, Jürgen; Rotmann, Andre-Robert; Hovhannisyan, Areg; Panossian, Alexander

doi:10.1016/j.phymed.2020.153218

Cited by 116 publications

(116 citation statements)

References 43 publications

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“…Adjuvant therapy involving the use of curcumin with conventional anticancer drugs, including doxorubicin, paclitaxel, cisplatin, etoposide, 5-fluorouracil, docetaxel, mitomycin C, tamoxifen, and cyclophosphamide is reported to enhance the chemotherapeutic effect of the latter. Curcumin acts by reducing transcriptional activation of the Pgp promoter (p65/p50) and inhibition of the CYP enzymes (CYP3A4, CYP2D6) ( Saghatelyana et al, 2020 ) that are involved in drug metabolism. Curcumin also reduced cancer metastasis and suppressed expression of MMP-9, NF-kB, and COX-2 when administered in combination with other chemotherapeutic agents ( Wilken et al, 2011 ; Wang et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Enhancing Bioavailability and Stability of Curcumin Using Solid Lipid Nanoparticles (CLEN): A Covenant for Its Effectiveness

Gupta

Singh

Kaur

et al. 2020

Front. Bioeng. Biotechnol.

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Curcumin, very rightly referred to as "a wonder drug" is proven to be efficacious in a variety of inflammatory disorders including cancers. Antiaging, anti-inflammatory, antioxidant, antitumor, chemosensitizing, P-gp efflux inhibiting, and antiproliferative activity are some of the striking features of curcumin, highlighting its importance in chemotherapy. Curcumin inhibits Bcl-2, Bcl-XL, VEGF, c-Myc, ICAM-1, EGFR, STAT3 phosphorylation, and cyclin D1 genes involved in the various stages of breast, prostate, and gastric cancer proliferation, angiogenesis, invasion, and metastasis. The full therapeutic potential of curcumin however remains under explored mainly due to poor absorption, rapid metabolism and systemic elimination culminating in its poor bioavailability. Furthermore, curcumin is insoluble, unstable at various pH and is also prone to undergo photodegradation. Nanotechnology can help improve the therapeutic potential of drug molecules with compromised biopharmaceutical profiles. Solid lipid nanoparticles (SLNs) are the latest offshoot of nanomedicine with proven advantages of high drug payload, longer shelf life, biocompatibility and biodegradability, and industrial amenability of the production process. We successfully developed CLEN (Curcumin encapsulated lipidic nanoconstructs) containing 15 mg curcumin per ml of the SLN dispersion with highest (till date, to our knowledge) increase in solubility of curcumin in an aqueous system by 1.4 × 10 6 times as compared to its intrinsic solubility of 11 ng/ml and high drug loading (15% w/v with respect to lipid matrix). Zero-order release kinetics observed for CLEN versus first order release for free curcumin establish controlled release nature of the developed CLEN. It showed 69.78 times higher oral bioavailability with respect to free curcumin; 9.00 times higher than a bioavailable marketed formulation (CurcuWIN R). The formulation showed 104, 13.3, and 10-times enhanced stability at pH 6.8, 1.2, and 7.4, respectively. All these factors ensure the efficacy of CLEN in treating cancer and other inflammatory diseases.

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Section: Introductionmentioning

confidence: 99%

Enhancing Bioavailability and Stability of Curcumin Using Solid Lipid Nanoparticles (CLEN): A Covenant for Its Effectiveness

Gupta

Singh

Kaur

et al. 2020

Front. Bioeng. Biotechnol.

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“…Similar effects were observed in a II phase study, where curcumin was tested as complementary treatment of paclitaxel in metastatic and advanced breast cancer. The treatment with both compounds was more efficient compared with paclitaxel-placebo and no toxic effects were observed [83]. As a function of these results, it seems guaranteed that curcumin could be used in combination with the conventional drugs to enhance their efficacy in the future.…”

Section: Curcuminmentioning

confidence: 79%

Status and Challenges of Plant-Anticancer Compounds in Cancer Treatment

et al. 2021

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Nowadays, cancer is one of the deadliest diseases in the world, which has been estimated to cause 9.9 million deaths in 2020. Conventional treatments for cancer commonly involve mono-chemotherapy or a combination of radiotherapy and mono-chemotherapy. However, the negative side effects of these approaches have been extensively reported and have prompted the search of new therapeutic drugs. In this context, scientific community started to look for innovative sources of anticancer compounds in natural sources, including traditional plants. Currently, numerous studies have evaluated the anticancer properties of natural compounds derived from plants, both in vitro and in vivo. In pre-clinical stages, some promising compounds could be mentioned, such as the sulforaphane or different phenolic compounds. On the other hand, some phytochemicals obtained positive results in clinical stages and were further approved for cancer treatment, such as vinca alkaloids or the paclitaxel. Nevertheless, these compounds are not exempt of limitations, such as low solubility, restricted effect on their own, negative side-effects, etc. This review aims to compile the information about the current phytochemicals used for cancer treatment and also promising candidates, main action mechanisms and also reported limitations. In this sense, some strategies to face the limitations have been considered, such as nano-based formulations to improve solubility or chemical modification to reduce toxicity. In conclusion, although more research is still necessary to develop more efficient and safe phytochemical drugs, more of these compounds might be used in future cancer therapies.

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“…Curcumin (from Curcuma longa) and Nigella sativa extracts were mentioned twice, respectively. (Martinez, et al, 2018;Saghatelyan, et al, 2020;Rafati, et al, 2019;Huseini, et al, 2016). Those trials showed encouraging results from respective plants, opening the possibility to explore the efficacy, safety and toxicity deeper into bigger population.…”

Section: Discussionmentioning

confidence: 99%

“…Another less popular compound in Curcuma longa is aromatic turmeron which has been shown to suppress TPA-induced up-regulation of MMP-9 and COX-2 expression by blocking NF-kB, PI3K/Akt, and ERK1/2 signaling in human breast cancer cells (Park, et al, 2012). Aside from the basic research, clinical studies showed that curcumin also had a promising future (Martinez, et al, 2018;Saghatelyan, et al, 2020). Curcuma zanthorrhiza is also known locally in some part of Indonesia as "temulawak".…”

Section: Curcuma Zedoariamentioning

confidence: 99%

Revealing Chemopreventive Potential of Active Constituents from Medicinal Herbs Used in Indonesia for (Metastatic) Breast Cancer with Particular Molecular Targets

Indrasetiawan

Haryanti²,

Meiyanto

2020

Indones J Cancer Chemoprevent

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Breast cancer remains as one of the highest causes of cancer-related deaths in the world, including Indonesia. In spite of following the standard protocol therapy, some patients in developing countries consume medicinal herbs as an alternative, complementary, as well as supportive therapies. Several herbs have been recognized to be used for this purpose. Annona muricata, Curcuma longa, Curcuma zanthorrhiza, Curcuma zedoaria, Phyllanthus urinaria, Gynura procumbens, Garcinia mangostana, Morinda citrifolia, and Nigella sativa are some of the plants used as chemopreventive agents with several formulas. Various types of extracts of Annona muricata show anticancer activities in vitro and in vivo. Curcumin, obtained from Curcuma longa and Curcuma zanthorrhiza, acts as p53 regulator and pro-oxidant in MCF-7 cells and also acts as a fatty acid synthase inhibitor in MDA-MB-231 cells. Xanthorrhizol from Curcuma zanthorrhiza has pro-apoptotic activity via modulation of Bcl-2, p53, and PARP-1 protein levels. Curcuma zedoaria contains curcumenone, curcumenol and curdion, which show pro-apoptotic activity in various cell lines and a cancer-induced mouse model. Corilagin and geraniin from Phyllanthus urinaria have different pro-apoptotic effects, in which, the corilagin-caused apoptotic effect is mediated by extrinsic and mitochondrial pathways, whereas geraniin induces apoptosis via ROS-mediated stimulation, both in MCF-7 cells. Thymoquinone from Nigella sativa has been extensively studied for its anticancer activities in recent years. Plants are cultivated, collected and mixed depending on the use as herbal medicines. Active compounds might be formulated if deemed possible. The development of more potential derivatives is also necessary to produce more optimum anti-cancer agents. In conclusion, Indonesian plants and their active constituents show potential activities to be developed as chemopreventive agents.Keywords: Indonesian medicinal herbs, breast cancer, active constituents, molecular targets

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Efficacy and safety of curcumin in combination with paclitaxel in patients with advanced, metastatic breast cancer: A comparative, randomized, double-blind, placebo-controlled clinical trial

Cited by 116 publications

References 43 publications

Enhancing Bioavailability and Stability of Curcumin Using Solid Lipid Nanoparticles (CLEN): A Covenant for Its Effectiveness

Enhancing Bioavailability and Stability of Curcumin Using Solid Lipid Nanoparticles (CLEN): A Covenant for Its Effectiveness

Status and Challenges of Plant-Anticancer Compounds in Cancer Treatment

Revealing Chemopreventive Potential of Active Constituents from Medicinal Herbs Used in Indonesia for (Metastatic) Breast Cancer with Particular Molecular Targets

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