A gallotannin-rich fraction from Caesalpinia spinosa (Molina) Kuntze displays cytotoxic activity and raises sensitivity to doxorubicin in a leukemia cell line

Abstract

BackgroundEnhancement of tumor cell sensitivity may help facilitate a reduction in drug dosage using conventional chemotherapies. Consequently, it is worthwhile to search for adjuvants with the potential of increasing chemotherapeutic drug effectiveness and improving patient quality of life. Natural products are a very good source of such adjuvants.MethodsThe biological activity of a fraction enriched in hydrolysable polyphenols (P2Et) obtained from Caesalpinia spinosa was evaluated using the hematopoietic cell line K562. This fraction was tested alone or in combination with the conventional chemotherapeutic drugs doxorubicin, vincristine, etoposide, camptothecin and taxol. The parameters evaluated were mitochondrial depolarization, caspase 3 activation, chromatin condensation and clonogenic activity.ResultsWe found that the P2Et fraction induced mitochondrial depolarization, activated caspase 3, induced chromatin condensation and decreased the clonogenic capacity of the K562 cell line. When the P2Et fraction was used in combination with chemotherapeutic drugs at sub-lethal concentrations, a fourfold reduction in doxorubicin inhibitory concentration 50 (IC50) was seen in the K562 cell line. This finding suggested that P2Et fraction activity is specific for the molecular target of doxorubicin.ConclusionsOur results suggest that a natural fraction extracted from Caesalpinia spinosa in combination with conventional chemotherapy in combination with natural products on leukemia cells may increase therapeutic effectiveness in relation to leukemia.

Multifunctional T Lymphocytes Generated After Therapy With an Antitumor Gallotanin-Rich Normalized Fraction Are Related to Primary Tumor Size Reduction in a Breast Cancer Model

“…It induces apoptosis in several tumor cells and sensitizes K562 (chronic myelogenous leukemia) cells to doxorubicin (DX)-induced death. 21 Treatment with the P2Et fraction improves primary tumor control and decreases the number of metastatic cells in the spleen and lung in the highly invasive and poorly immunogenic murine breast adenocarcinoma cell line, 4T1; these decreases are concomitant with a reduction of interleukin (IL)-6 serum levels. 22 In the present study, we provide evidence demonstrating that a specific IR is generated by this natural fraction, preceded by HMGB-1 mobilization and CRT expression on the plasma membrane of 4T1 tumor cells.…”

“…USA), as previously reported. 21 Triplicate samples were acquired on a FACSAria II (Becton Dickinson, San Jose, CA, USA) and analyzed with FlowJo software (Tree Star Inc, Ashland, OR, USA).…”

“…In the breast cancer cell line MCF7, the P2Et fraction exhibited adjuvant activities when combined with all the tested drugs, suggesting a specific mechanism related to the biological characteristics of cell lines. 21 Recently, we demonstrated that the P2Et fraction was also active in 4T1 cells via the same mitochondrial-dependent mechanisms, delaying in vivo primary tumor growth and metastasis. 22 Several mechanisms can be implicated in this antitumor activity.…”

La fitoterapia como fuente de medicamentos reguladores del metabolismo tumoral y activadores de la respuesta inmunitaria

“…Además, cuando se usó en conjunto con fármacos quimioterapéuticos como la doxorubicina en concentraciones no letales, se observó una reducción de la IC 50 , lo que representa un aumento en la actividad antitumoral neta del medicamento, la cual se traduciría en la posibilidad de utilizar menos doxorubicina cuando se administre en asocio con el extracto de dividivi (Castañeda, et al, 2012;Urueña, et al, 2013) En el modelo in vivo, además, el extracto redujo el tumor primario de ratones BALB/c con trasplante ortotópico de células 4T1 de cáncer de seno y disminuyó las metástasis, doi: http://dx.doi.org/10.18257/raccefyn.542…”

Six new cassane diterpenes from the twigs and leaves of Tara (Caesalpinia spinosa Kuntze)

“…Studies have mainly been focused on the tannins of C. spinosa [3][4][5][6][7]. Few reports are available concerning the non-tanninic components of this species.…”