Antitumor effect of the combination of manumycin A and Immodin is associated with antiplatelet activity and increased granulocyte tumor infiltration in a 4T1 breast tumor model

Solár, Peter; Sačková, Veronika; Hrčková, Gabriela; Demečková, Vlasta; Kassayová, Monika; Bojková, Bianka; Mudroňová, Dagmar; Gancarčíková, Soňa; Jendželovský, Rastislav; Fedoročko, Peter

doi:10.3892/or.2016.5265

Cited by 16 publications

(15 citation statements)

References 73 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our previous study, T. vulgaris L., applied in the same mouse model and doses as cinnamon, demonstrated significant reduction of 4T1 tumor volume in mice by more than 80% compared to the control group [7]. Mentioned significant therapeutic effects of plant substances are comparable with the antitumor efficacy of several synthetic drugs tested in the 4T1 mouse model of breast cancer [36][37][38]. The results of this and our previous preclinical rodent model studies confirmed our scientific assumption that the significant anticancer effect of whole plant functional foods is based more on a combination of several phytochemicals than on isolated molecules [2][3][4][5][6][7]39,40].…”

Section: Discussionmentioning

confidence: 80%

Chemopreventive and Therapeutic Efficacy of Cinnamomum zeylanicum L. Bark in Experimental Breast Carcinoma: Mechanistic In Vivo and In Vitro Analyses

et al. 2020

View full text Add to dashboard Cite

Comprehensive oncology research suggests an important role of phytochemicals or whole plant foods in the modulation of signaling pathways associated with anticancer action. The goal of this study is to assess the anticancer activities of Cinnamomum zeylanicum L. using rat, mouse, and cell line breast carcinoma models. C. zeylanicum (as bark powder) was administered in the diet at two concentrations of 0.1% (w/w) and 1% (w/w) during the whole experiment in chemically induced rat mammary carcinomas and a syngeneic 4T1 mouse model. After autopsy, histopathological and molecular evaluations of mammary gland tumors in rodents were carried out. Moreover, in vitro analyses using MCF-7 and MDA-MB-231 cells were performed. The dominant metabolites present in the tested C. zeylanicum essential oil (with relative content over 1%) were cinnamaldehyde, cinnamaldehyde dimethyl acetal, cinnamyl acetate, eugenol, linalool, eucalyptol, limonene, o-cymol, and α-terpineol. The natural mixture of mentioned molecules demonstrated significant anticancer effects in our study. In the mouse model, C. zeylanicum at a higher dose (1%) significantly decreased tumor volume by 44% when compared to controls. In addition, treated tumors showed a significant dose-dependent decrease in mitotic activity index by 29% (0.1%) and 45.5% (1%) in comparison with the control group. In rats, C. zeylanicum in both doses significantly reduced the tumor incidence by 15.5% and non-significantly suppressed tumor frequency by more than 30% when compared to controls. An evaluation of the mechanism of anticancer action using valid oncological markers showed several positive changes after treatment with C. zeylanicum. Histopathological analysis of treated rat tumor specimens showed a significant decrease in the ratio of high-/low-grade carcinomas compared to controls. In treated rat carcinomas, we found caspase-3 and Bax expression increase. On the other hand, we observed a decrease in Bcl-2, Ki67, VEGF, and CD24 expressions and MDA levels. Assessment of epigenetic changes in rat tumor cells in vivo showed a significant decrease in lysine methylation status of H3K4m3 and H3K9m3 in the high-dose treated group, a dose-dependent increase in H4K16ac levels (H4K20m3 was not changed), down-regulations of miR21 and miR155 in low-dose cinnamon groups (miR22 and miR34a were not modulated), and significant reduction of the methylation status of two out of five gene promoters—ATM and TIMP3 (PITX2, RASSF1, PTEN promoters were not changed). In vitro study confirmed results of animal studies, in that the essential oil of C. zeylanicum displayed significant anticancer efficacy in MCF-7 and MDA-MB-231 cells (using MTS, BrdU, cell cycle, annexin V/PI, caspase-3/7, Bcl-2, PARP, and mitochondrial membrane potential analyses). As a conclusion, C. zeylanicum L. showed chemopreventive and therapeutic activities in animal breast carcinoma models that were also significantly confirmed by mechanistic evaluations in vitro and in vivo.

show abstract

Section: Discussionmentioning

confidence: 80%

Chemopreventive and Therapeutic Efficacy of Cinnamomum zeylanicum L. Bark in Experimental Breast Carcinoma: Mechanistic In Vivo and In Vitro Analyses

et al. 2020

View full text Add to dashboard Cite

show abstract

“…I-CRP shows selective cytotoxicity to solid cancer cells [16,20,21,23], such as MCF-7, BT-474, MDA-MB-453, A-427, Calu-1, U937, and L5178Y-R cell lines [20,21,23]. Other types of DLE have also shown antitumor activity in prostate cancer [29] and can be used in combination with chemotherapies [30] and with antibiotics as manumycin in mouse breast cancer (4T1) [31]. Since these cytotoxic analyses were done in solid cancer cell lines, its effect in cancer lymphocytes was unknown especially because there were doubts about its efficacy in leukemia, as it increases lymphocyte number in lung [14] and breast [15] cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Bovine Dialyzable Leukocyte Extract IMMUNEPOTENT-CRP Induces Selective ROS-Dependent Apoptosis in T-Acute Lymphoblastic Leukemia Cell Lines

Lorenzo-Anota

Martínez‐Torres

Scott‐Algara

et al. 2020

Journal of Oncology

View full text Add to dashboard Cite

Immunotherapies strengthen the immune system to fight multiple diseases such as infections, immunodeficiencies, and autoimmune diseases, and recently, they are being used as an adjuvant in cancer treatment. IMMUNEPOTENT-CRP (I-CRP) is an immunotherapy made of bovine dialyzable leukocyte extract (bDLE) that has chemoprotective and immunomodulatory effects in different cellular populations of the immune system and antitumor activity in different cancer cell lines. Our recent results suggest that the antineoplastic effect of I-CRP is due to the characteristics of cancer cells. To confirm, we evaluated whether the selectivity is due to cell lineage or characteristics of cancer cells, testing cytotoxicity in T-acute lymphoblastic leukemia cells and their cell death mechanism. Here, we assessed the effect of I-CRP on cell viability and cell death. To determine the mechanism of cell death, we tested cell cycle, mitochondrial and nuclear alterations, and caspases and reactive oxygen species (ROS) and their role in cell death mechanism. Our results show that I-CRP does not affect cell viability in noncancer cells and induces selective cytotoxicity in a dose-dependent manner in leukemic cell lines. I-CRP also induces mitochondrial damage through proapoptotic and antiapoptotic protein modulation (Bax and Bcl-2) and ROS production, nuclear alterations including DNA damage (γ-H2Ax), overexpression of p53, cell cycle arrest, and DNA degradation. I-CRP induced ROS-dependent apoptosis in leukemic cells. Overall, here, we show that I-CRP cytotoxicity is selective to leukemic cells, inducing ROS-dependent apoptosis. This research opens the door to further exploration of their role in the immune system and the cell death mechanism that could potentially work in conjunction with other therapies including hematological malignances.

show abstract

“…Manumycin A was isolated from Streptomyces [28], and inhibits the prenylation of small G-protein [29]. The administration of manumycin A prevented the growth of triple-negative breast cancers, in which the expressions of estrogen, progesterone, and HER2 receptors were negative, in nude mice [29].…”

Section: Acidosis-dependent Anti-cancer Drugsmentioning

confidence: 99%

“…The administration of manumycin A prevented the growth of triple-negative breast cancers, in which the expressions of estrogen, progesterone, and HER2 receptors were negative, in nude mice [29]. Manumycin A was also shown to increase the efficacy of other anti-cancer drugs in animal models [28]. To the best of the author’s knowledge, no clinical trial using manumycin A has been reported.…”

Section: Acidosis-dependent Anti-cancer Drugsmentioning

confidence: 99%

See 1 more Smart Citation

Cancer Chemotherapy Specific to Acidic Nests

Kobayashi

2017

Cancers

View full text Add to dashboard Cite

The realization of cancer therapeutics specific to cancer cells with less of an effect on normal tissues is our goal. Many trials have been carried out for this purpose, but this goal is still far from being realized. It was found more than 80 years ago that solid cancer nests are acidified, but in vitro studies under acidic conditions have not been extensively studied. Recently, in vitro experiments under acidic conditions were started and anti-cancer drugs specific to acidic areas have been identified. Many genes have been reported to be expressed at a high level under acidic conditions, and such genes may be potent targets for anti-cancer drugs specific to acidic nests. In this review article, recent in vitro, in vivo, and clinical achievements in anti-cancer drugs with marked efficacy under acidic conditions are summarized, and the clinical use of anti-cancer drugs specific to acidic nests is discussed.

show abstract

Antitumor effect of the combination of manumycin A and Immodin is associated with antiplatelet activity and increased granulocyte tumor infiltration in a 4T1 breast tumor model

Cited by 16 publications

References 73 publications

Chemopreventive and Therapeutic Efficacy of Cinnamomum zeylanicum L. Bark in Experimental Breast Carcinoma: Mechanistic In Vivo and In Vitro Analyses

Chemopreventive and Therapeutic Efficacy of Cinnamomum zeylanicum L. Bark in Experimental Breast Carcinoma: Mechanistic In Vivo and In Vitro Analyses

Bovine Dialyzable Leukocyte Extract IMMUNEPOTENT-CRP Induces Selective ROS-Dependent Apoptosis in T-Acute Lymphoblastic Leukemia Cell Lines

Cancer Chemotherapy Specific to Acidic Nests

Contact Info

Product

Resources

About