Plant-Derived Natural Products in Cancer Research: Extraction, Mechanism of Action, and Drug Formulation

Talib, Wamidh H.; Alsalahat, Izzeddin; Daoud, Safa; Abutayeh, Reem Fawaz; Mahmod, Asma Ismail

doi:10.3390/molecules25225319

Cited by 77 publications

(40 citation statements)

References 715 publications

(876 reference statements)

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“…Constituted by a mixture of proteases together with some other enzymes and proteins, there are some evidence of potential benefits of bromelain in cancer treatment 29 . In our study, we evaluate the antiproliferative effect of the free and nanoencapsulated commercial bromelain in a panel of eight human tumor cell lines of different histological or genetic origins and one human non-tumor cell line (Table 1 , Fig.…”

Section: Resultsmentioning

confidence: 99%

In vitro performance of free and encapsulated bromelain

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Figueiredo

et al. 2021

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For centuries, bromelain has been used to treat a range of ailments, even though its mechanism of action is not fully understood. Its therapeutic benefits include enzymatic debridement of the necrotic tissues of ulcers and burn wounds, besides anti-inflammatory, anti-tumor, and antioxidant properties. However, the protease is unstable and susceptible to self-hydrolysis over time. To overcome the stability issues of bromelain, a previous study formulated chitosan-bromelain nanoparticles (C-B-NP). We evaluated the optimized nanoformulation for in vitro antioxidant, cell antiproliferative activities and cell migration/proliferation in the scratch assay, comparing it with free bromelain. The antioxidant activity of free bromelain was concentration and time-dependent; after encapsulation, the activity level dropped, probably due to the slow release of protein from the nanoparticles. In vitro antiproliferative activity was observed in six tumor cell lines for free protein after 48 h of treatment (glioma, breast, ovarian, prostate, colon adenocarcinoma and chronic myeloid leukemia), but not for keratinocyte cells, enabling its use as an active topical treatment. In turn, C-B-NP only inhibited one cell line (chronic myeloid leukemia) and required higher concentrations for inhibition. After 144 h treatment of glioma cells with C-B-NP, growth inhibition was equivalent to that promoted by the free protein. This last result confirmed the delayed-release kinetics of the optimized formulation and bromelain integrity. Finally, a scratch assay with keratinocyte cells showed that C-B-NP achieved more than 90% wound retraction after 24 h, compared to no retraction with the free bromelain. Therefore, nanoencapsulation of bromelain with chitosan conferred physical protection, delayed release, and wound retraction activity to the formulation, properties that favor topical formulations with a modified release. In addition, the promising results with the glioma cell line point to further studies of C-B-NP for anti-tumor treatments.

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Section: Resultsmentioning

confidence: 99%

In vitro performance of free and encapsulated bromelain

Ataide

Cefali

Figueiredo

et al. 2021

Sci Rep

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“…The phosphorylation of p62 correlates autophagy with the Nrf2/kelch-like ECH-associated protein 1 (Keap-1) signaling pathway. When autophagy is compromised, the competition between p62 accumulation and Nrf2 combination with keap-1 leads to the nuclear translocation of Nrf2 dissociation, promoting the continuous activation of the Nrf2 signal pathway and p62 accumulation, while the p62-Keap-1 complex is isolated in autophagosomes and degraded by autophagy [ 165 ]. Specifically, unlike pancreatic cancer PANC1 cells, in PaCa44 cells, mutant p53 stabilizes through its interaction with HSP90, activating the positive feedback loop between Nrf2 and p62, and thereby inducing chemotherapy resistance to apigenin, as shown in Figure 3 B [ 42 ].…”

Section: Targeting Autophagy Regulates Mdrmentioning

confidence: 99%

Autophagy: Mechanisms and Therapeutic Potential of Flavonoids in Cancer

et al. 2021

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Autophagy, which is a conserved biological process and essential mechanism in maintaining homeostasis and metabolic balance, enables cells to degrade cytoplasmic constituents through lysosomes, recycle nutrients, and survive during starvation. Autophagy exerts an anticarcinogenic role in normal cells and inhibits the malignant transformation of cells. On the other hand, aberrations in autophagy are involved in gene derangements, cell metabolism, the process of tumor immune surveillance, invasion and metastasis, and tumor drug-resistance. Therefore, autophagy-targeted drugs may function as anti-tumor agents. Accumulating evidence suggests that flavonoids have anticarcinogenic properties, including those relating to cellular proliferation inhibition, the induction of apoptosis, autophagy, necrosis, cell cycle arrest, senescence, the impairment of cell migration, invasion, tumor angiogenesis, and the reduction of multidrug resistance in tumor cells. Flavonoids, which are a group of natural polyphenolic compounds characterized by multiple targets that participate in multiple pathways, have been widely studied in different models for autophagy modulation. However, flavonoid-induced autophagy commonly interacts with other mechanisms, comprehensively influencing the anticancer effect. Accordingly, targeted autophagy may become the core mechanism of flavonoids in the treatment of tumors. This paper reviews the flavonoid-induced autophagy of tumor cells and their interaction with other mechanisms, so as to provide a comprehensive and in-depth account on how flavonoids exert tumor-suppressive effects through autophagy.

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“…Emodin is most widely isolated from the Rheum palmatum (Chinese rhubarb, family: Polygonaceae) roots and rhizomes. It is also existed in Polygonum multiflorum (Chinese knotweed), Polygonum cuspidatum (Asian knotweed), Cassia obtusifolia (Chinese senna, family: Fabaceae), Aloe vera (family: Asphodelaceae), Aspergillus wentii, and Aspergillus ochraceus [ 206 , 207 , 208 , 209 ]. Emodin (1,3,8-trihydroxy-6-methyl-anthraquinone) is a natural derivative of anthraquinone [ 210 ].…”

Section: Natural Products Targeting Diabetes and Cancermentioning

confidence: 99%

Diabetes and Cancer: Metabolic Association, Therapeutic Challenges, and the Role of Natural Products

et al. 2021

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Cancer is considered the second leading cause of death worldwide and in 2018 it was responsible for approximately 9.6 million deaths. Globally, about one in six deaths are caused by cancer. A strong correlation was found between diabetes mellitus and carcinogenesis with the most evident correlation was with type 2 diabetes mellitus (T2DM). Research has proven that elevated blood glucose levels take part in cell proliferation and cancer cell progression. However, limited studies were conducted to evaluate the efficiency of conventional therapies in diabetic cancer patients. In this review, the correlation between cancer and diabetes will be discussed and the mechanisms by which the two diseases interact with each other, as well as the therapeutics challenges in treating patients with diabetes and cancer with possible solutions to overcome these challenges. Natural products targeting both diseases were discussed with detailed mechanisms of action. This review will provide a solid base for researchers and physicians to test natural products as adjuvant alternative therapies to treat cancer in diabetic patients.

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Plant-Derived Natural Products in Cancer Research: Extraction, Mechanism of Action, and Drug Formulation

Cited by 77 publications

References 715 publications

In vitro performance of free and encapsulated bromelain

In vitro performance of free and encapsulated bromelain

Autophagy: Mechanisms and Therapeutic Potential of Flavonoids in Cancer

Diabetes and Cancer: Metabolic Association, Therapeutic Challenges, and the Role of Natural Products

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