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23 pages, 2370 KiB

Open AccessArticle

Exploring Water-Soluble South African Tulbaghia violacea Harv Extract as a Therapeutic Approach for Triple-Negative Breast Cancer Metastasis

by Mohammed Alaouna, Rodney Hull, Thulo Molefi, Richard Khanyile, Langanani Mbodi, Thifhelimbilu Emmanuel Luvhengo, Nkhensani Chauke-Malinga, Boitumelo Phakathi, Clement Penny and Zodwa Dlamini

Curr. Issues Mol. Biol. 2024, 46(10), 10806-10828; https://doi.org/10.3390/cimb46100642 - 26 Sep 2024

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Abstract

Triple-negative breast cancer (TNBC) accounts for approximately 20% of all breast cancer cases and is characterized by a lack of estrogen, progesterone, and human epidermal growth factor 2 receptors. Current targeted medicines have been unsuccessful due to this absence of hormone receptors. This [...] Read more.

Triple-negative breast cancer (TNBC) accounts for approximately 20% of all breast cancer cases and is characterized by a lack of estrogen, progesterone, and human epidermal growth factor 2 receptors. Current targeted medicines have been unsuccessful due to this absence of hormone receptors. This study explored the efficacy of Tulbaghia violacea, a South African medicinal plant, for the treatment of TNBC metastasis. Extracts from T. violacea leaves were prepared using water and methanol. However, only the water-soluble extract showed anti-cancer activity and the effects of this water-soluble extract on cell adhesion, invasion, and migration, and its antioxidant activity were assessed using MCF-10A and MDA-MB-231 cells. The T. violacea extract that was soluble in water effectively decreased the movement and penetration of MDA-MB-231 cells through the basement membrane in scratch and invasion tests, while enhancing their attachment to a substance resembling an extracellular matrix. The sample showed mild-to-low antioxidant activity in the antioxidant assy. Nuclear magnetic resonance spectroscopy revealed 61 chemical components in the water-soluble extract, including DDMP, 1,2,4-triazine-3,5(2H,4H)-dione, vanillin, schisandrin, taurolidine, and α-pinene, which are known to have anti-cancer properties. An in-depth examination of the transcriptome showed alterations in genes linked to angiogenesis, metastasis, and proliferation post-treatment, with reduced activity in growth receptor signaling, angiogenesis, and cancer-related pathways, such as the Wnt, Notch, and PI3K pathways. These results indicate that T. violacea may be a beneficial source of lead chemicals for the development of potential therapeutic medicines that target TNBC metastasis. Additional studies are required to identify the precise bioactive chemical components responsible for the observed anti-cancer effects. Full article

(This article belongs to the Special Issue Phytochemicals in Cancer Chemoprevention and Treatment)

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14 pages, 2985 KiB

Open AccessArticle

Honokiol Is More Potent than Magnolol in Reducing Head and Neck Cancer Cell Growth

by Robert Kleszcz, Dawid Dorna, Maciej Stawny and Jarosław Paluszczak

Curr. Issues Mol. Biol. 2024, 46(10), 10731-10744; https://doi.org/10.3390/cimb46100637 - 25 Sep 2024

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Abstract

The efficacy of treatment of head and neck squamous cell carcinoma (HNSCC) patients is still unsatisfactory, and there is an ongoing search for novel therapies. Locoregionally advanced HNSCC cases, which frequently require combined surgery and chemoradiotherapy, are especially difficult to treat. Natural compounds, [...] Read more.

The efficacy of treatment of head and neck squamous cell carcinoma (HNSCC) patients is still unsatisfactory, and there is an ongoing search for novel therapies. Locoregionally advanced HNSCC cases, which frequently require combined surgery and chemoradiotherapy, are especially difficult to treat. Natural compounds, like Magnolia-derived lignans—honokiol (HON) and magnolol (MAG)—can reduce cancer cell growth but retain a good safety profile and thus may show benefit as adjuvant therapeutics. The aim of this study was to evaluate the anti-cancer effects of HON and MAG in HNSCC cell lines and compare their effects between cisplatin-sensitive and cisplatin-tolerant cells. Cell viability was evaluated in FaDu and SCC-040 cells growing as monolayers and as spheroids. The effect of HON and MAG on the cell cycle, apoptosis, and gene expression was compared between wild-type FaDu cells and cisplatin persister FaDu cells. We observed that HON and MAG were more potent in reducing cell viability in cisplatin persister FaDu cells, although this effect was not directly followed by increased rates of apoptosis. Thus, HON’s and MAG’s capacity to affect cisplatin persister cells needs further studies. In general, we observed that HON exerted stronger cytotoxic effects than MAG in HNSCC cells, and the difference in their anti-cancer activity was especially pronounced in cells cultured in 3D. Full article

(This article belongs to the Special Issue Phytochemicals in Cancer Chemoprevention and Treatment)

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23 pages, 11085 KiB

Open AccessArticle

Exopolysaccharides from the Green Microalga Strain Coelastrella sp. BGV—Isolation, Characterization, and Assessment of Anticancer Potential

by Tanya Toshkova-Yotova, Inna Sulikovska, Vera Djeliova, Zdravka Petrova, Manol Ognyanov, Petko Denev, Reneta Toshkova and Ani Georgieva

Curr. Issues Mol. Biol. 2024, 46(9), 10312-10334; https://doi.org/10.3390/cimb46090614 - 16 Sep 2024

Viewed by 620

Abstract

Algal metabolites have been extensively studied as potential anticancer therapeutics. Among them, polysaccharides have attracted much attention because of their beneficial biological effects and safety. In the present research, the chemical characteristics, antitumor, and proapoptotic activities of extracellular polysaccharides (EPS) isolated from a [...] Read more.

Algal metabolites have been extensively studied as potential anticancer therapeutics. Among them, polysaccharides have attracted much attention because of their beneficial biological effects and safety. In the present research, the chemical characteristics, antitumor, and proapoptotic activities of extracellular polysaccharides (EPS) isolated from a new Bulgarian strain of the green microalga Coelastrella sp. BGV were investigated. A fast and convenient method of precipitation with cold ethanol was used to isolate EPS from the culture medium. The chemical characteristics of the isolated EPS were examined by colorimetric and spectrophotometric analyses, HPSEC-RID and HPLC-UV chromatography, and FT-IR spectroscopy. The results showed that the isolated EPS sample consists of three carbohydrate fractions with different molecular weights (11.5 × 10⁴ Da, 30.7 × 10⁴ Da, and 72.4 × 10⁴ Da, respectively) and contains 7.14 (w/w%) protein. HPLC-UV analysis revealed the presence of galactose and fucose. The total uronic acid content in the sample was 4.5 (w/w%). The IR-FT spectrum of EPS revealed the presence of various functional groups typical of a polysaccharide (or proteoglycan) composed primarily of neutral sugars. The anticancer potential of the obtained EPS was assessed using cell lines with cancerous and non-cancerous origins as in vitro experimental models. The results of the performed MTT assay showed that EPS reduced the viability of the cervical and mammary carcinoma cell lines HeLa and MCF-7, while the control non-cancer cell lines BALB/3T3 and HaCaT were less affected. The HeLa cell line showed the highest sensitivity to the effects of EPS and was therefore used for further studies of its anticancer potential. The ability of EPS to inhibit cancer cell migration was demonstrated by wound-healing (scratch) assay. The cell cycle FACS analysis indicated that the EPS treatment induced significant increases in the sub G1 cell population and decreases of the percentages of cells in the G1, S, and G2-M phases, compared to the control. The fluorescent microscopy studies performed using three different staining methods in combination with Annexin V-FITC flow cytometric analysis clearly demonstrate the ability of EPS to induce cancer cell death via the apoptosis pathway. Moreover, an altered pattern and intensity of the immunocytochemical staining for the apoptosis- and proliferation-related proteins p53, bcl2, and Ki67 was detected in EPS-treated HeLa cancer cells as compared to the untreated controls. The obtained results characterize the new local strain of green microalgae Coelastrella sp. BGV as a producer of EPS with selective antitumor activity and provide an opportunity for further studies of its pharmacological and biotechnological potential. Full article

(This article belongs to the Special Issue Phytochemicals in Cancer Chemoprevention and Treatment)

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14 pages, 6572 KiB

Open AccessArticle

Cacalol Acetate as Anticancer Agent: Antiproliferative, Pro-Apoptotic, Cytostatic, and Anti-Migratory Effects

by Gareth Omar Rostro-Alonso, Alejandro Israel Castillo-Montoya, Juan Carlos García-Acosta, Erick Fernando Aguilar-Llanos, Laura Itzel Quintas-Granados, Edgar Yebrán Villegas-Vazquez, Rosario García-Aguilar, Samantha Andrea Porras-Vázquez, Lilia Patricia Bustamante-Montes, Jesús J. Alvarado-Sansininea, Manuel Jiménez-Estrada, Lizbeth Cariño-Calvo, Manuel González-del Carmen, Hernán Cortés, Gerardo Leyva-Gómez, Gabriela Figueroa-González and Octavio Daniel Reyes-Hernández

Curr. Issues Mol. Biol. 2024, 46(9), 9298-9311; https://doi.org/10.3390/cimb46090550 - 23 Aug 2024

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Abstract

Cacalol (C), a sesquiterpene isolated from Psacalium decompositum, has demonstrated anti-inflammatory and antioxidant activities. Its cytotoxic, antiproliferative, and pro-apoptotic effects have been previously shown in an in vitro breast cancer model. A derivative, cacalol acetate (CA), shows potential in regulating these processes, [...] Read more.

Cacalol (C), a sesquiterpene isolated from Psacalium decompositum, has demonstrated anti-inflammatory and antioxidant activities. Its cytotoxic, antiproliferative, and pro-apoptotic effects have been previously shown in an in vitro breast cancer model. A derivative, cacalol acetate (CA), shows potential in regulating these processes, which has not been previously reported. This study focused on an in vitro cervical cancer model, assessing CA’s antiproliferative, pro-apoptotic, cytostatic, and anti-migratory activities using the HeLa cell line. The natural anticancer agent indole-3-carbinol (I3C) was used as a control for comparison. CA demonstrated significant antitumor activities, including inhibiting cell growth, inducing apoptosis, arresting cells in the G2 phase of the cell cycle, and inhibiting cell migration. These effects were notably greater compared to I3C. I3C, while following a similar trend, did not induce Cas-3 expression, suggesting a different apoptotic pathway. Neither CA nor I3C increased p62 and LC3B levels, indicating they do not stimulate autophagy marker expression. Both compounds inhibited HeLa cell migration and induced cell cycle arrest. Despite both holding promise as anticancer agents for cervical cancer, CA’s lower cytotoxicity and stronger regulation of tumor phenotypes make it a more promising agent compared to I3C. Full article

(This article belongs to the Special Issue Phytochemicals in Cancer Chemoprevention and Treatment)

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15 pages, 2019 KiB

Open AccessArticle

Inflammation Factors and Genistein Supplementation in Cancer—Preliminary Research

by Karolina Banyś, Małgorzata Jelińska, Małgorzata Wrzosek, Dorota Skrajnowska, Robert Wrzesień, Wojciech Bielecki and Barbara Bobrowska-Korczak

Curr. Issues Mol. Biol. 2024, 46(3), 2166-2180; https://doi.org/10.3390/cimb46030140 - 7 Mar 2024

Cited by 2 | Viewed by 1249

Abstract

The purpose of this study was to evaluate the effect of genistein in nano, micro, and macro forms on the intensity of the DMBA-induced tumor process in rats and to understand the mechanisms of this action. The effect of genistein supplementation on the [...] Read more.

The purpose of this study was to evaluate the effect of genistein in nano, micro, and macro forms on the intensity of the DMBA-induced tumor process in rats and to understand the mechanisms of this action. The effect of genistein supplementation on the content of selected eicosanoids (HETEs, HODE, and HEPE) in the serum of rats was evaluated. The levels and expression of genes encoding various pro-inflammatory cytokines (IL-1, IL-6) and MMP-9 in the blood of rats were also investigated. The biological material for the study was blood obtained from female rats of the Sprague Dawley strain (n = 32). The animals were randomly divided into four groups: animals without supplementation, and animals supplemented at a dose of 0.2 mg/kg b.w. (0.1 mg/mL) with macro, micro (587 ± 83 nm), or nano (92 ± 41 nm) genistein. To induce mammary neoplasia (adenocarcinoma), rats were given 7,12-dimethyl-1,2-benz[a]anthracene (DMBA). The content of selected eicosanoids was determined by liquid chromatography with UV detection. An immunoenzymatic method was used to determine the content of cytokines and MMP-9. The expression of the IL-6, IL-1beta, and MMP-9 genes was determined with quantitative real-time PCR (qRT-PCR) using TaqMan probes. Based on the study, it was shown that supplementation of animals with genistein in macro, micro, and nano forms increased the intensity of the tumor process in rats. It was shown that the content of 12-HEPE, HODE, and 12-HETE in the serum of genistein-supplemented rats was statistically significantly lower with respect to the content of the aforementioned markers in the serum of rats receiving only a standard diet, devoid of supplementation. It was found that animals supplemented with nano-, micro-, and macrogenistein had higher levels of metalloproteinase-9, MMP-9, compared to animals without supplementation. There was a significant increase in MMP-9 gene expression in the blood of macrogenistein-supplemented animals, relative to the other groups of rats. On the basis of the study, it was shown that supplementation of animals with nano-, micro-, and macrogenistein had an effect on the development of the tumor process. Dietary supplementation with genistein significantly decreased the level of selected eicosanoids, which may have significant impacts on cancer development and progression. Full article

(This article belongs to the Special Issue Phytochemicals in Cancer Chemoprevention and Treatment)

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Review

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21 pages, 2119 KiB

Open AccessReview

Modulation of Multidrug Resistance Transporters by Food Components and Dietary Supplements: Implications for Cancer Therapy Efficacy and Safety

by Agnieszka Brodzicka, Agnieszka Galanty and Paweł Paśko

Curr. Issues Mol. Biol. 2024, 46(9), 9686-9706; https://doi.org/10.3390/cimb46090576 - 2 Sep 2024

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Abstract

The aim of this review is to explore how diet and dietary supplements influence the activity of key multidrug resistance (MDR) transporters—MRP2, BCRP, and P-gp. These transporters play a crucial role in drug efflux from cancer cells and significantly affect chemotherapy outcomes. This [...] Read more.

The aim of this review is to explore how diet and dietary supplements influence the activity of key multidrug resistance (MDR) transporters—MRP2, BCRP, and P-gp. These transporters play a crucial role in drug efflux from cancer cells and significantly affect chemotherapy outcomes. This review focuses on how dietary phytochemicals, such as catechins and quercetin, impact the expression and function of these transporters. Both in vitro and in vivo experiments were examined to assess changes in drug bioavailability and intracellular drug accumulation. The findings show that certain dietary components—such as catechins, flavonoids, resveratrol, curcumin, terpenoids, sterols, and alkaloids—can either inhibit or induce MDR transporter activity, thus influencing the effectiveness of chemotherapy. These results highlight the importance of understanding diet–drug interactions in cancer therapy to improve treatment outcomes and reduce side effects. In conclusion, dietary modifications and supplements should be carefully considered in cancer treatment plans to optimize therapeutic efficacy. Full article

(This article belongs to the Special Issue Phytochemicals in Cancer Chemoprevention and Treatment)

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18 pages, 1825 KiB

Open AccessReview

Ashwagandha-Induced Programmed Cell Death in the Treatment of Breast Cancer

by Renata Kołodziejska, Agnieszka Tafelska-Kaczmarek, Mateusz Pawluk, Krzysztof Sergot, Lucyna Pisarska, Alina Woźniak and Hanna Pawluk

Curr. Issues Mol. Biol. 2024, 46(7), 7668-7685; https://doi.org/10.3390/cimb46070454 - 18 Jul 2024

Cited by 1 | Viewed by 1647

Abstract

The aim of this review is to provide experimental evidence for the programmed-death activity of Ashwagandha (Withania somnifera) in the anti-cancer therapy of breast cancer. The literature search was conducted using online electronic databases (Google Scholar, PubMed, Scopus). Collection schedule data [...] Read more.

The aim of this review is to provide experimental evidence for the programmed-death activity of Ashwagandha (Withania somnifera) in the anti-cancer therapy of breast cancer. The literature search was conducted using online electronic databases (Google Scholar, PubMed, Scopus). Collection schedule data for the review article covered the years 2004–2024. Ashwagandha active substances, especially Withaferin A (WA), are the most promising anti-cancer compounds. WS exerts its effect on breast cancer cells by inducing programmed cell death, especially apoptosis, at the molecular level. Ashwagandha has been found to possess a potential for treating breast cancer, especially estrogen receptor/progesterone receptor (ER/PR)-positive and triple-negative breast cancer. Full article

(This article belongs to the Special Issue Phytochemicals in Cancer Chemoprevention and Treatment)

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20 pages, 1434 KiB

Open AccessReview

Chemopreventive Agents from Nature: A Review of Apigenin, Rosmarinic Acid, and Thymoquinone

by Reem Fawaz Abutayeh, Maram Altah, Amani Mehdawi, Israa Al-Ataby and Adel Ardakani

Curr. Issues Mol. Biol. 2024, 46(7), 6600-6619; https://doi.org/10.3390/cimb46070393 - 27 Jun 2024

Viewed by 1037

Abstract

Cancer, a major challenge to global health and healthcare systems, requires the study of alternative and supportive treatments due to the limitations of conventional therapies. This review examines the chemopreventive potential of three natural compounds: rosmarinic acid, apigenin, and thymoquinone. Derived from various [...] Read more.

Cancer, a major challenge to global health and healthcare systems, requires the study of alternative and supportive treatments due to the limitations of conventional therapies. This review examines the chemopreventive potential of three natural compounds: rosmarinic acid, apigenin, and thymoquinone. Derived from various plants, these compounds have demonstrated promising chemopreventive properties in in vitro, in vivo, and in silico studies. Specifically, they have been shown to inhibit cancer cell growth, induce apoptosis, and modulate key signaling pathways involved in cancer progression. The aim of this review is to provide a comprehensive overview of the current research on these phytochemicals, elucidating their mechanisms of action, therapeutic efficacy, and potential as adjuncts to traditional cancer therapies. This information serves as a valuable resource for researchers and healthcare providers interested in expanding their knowledge within the field of alternative cancer therapies. Full article

(This article belongs to the Special Issue Phytochemicals in Cancer Chemoprevention and Treatment)

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