Prediction of anticancer peptides derived from the true lectins of Phoenix dactylifera and their synergetic effect with mitotane

Abstract

Background and aims: Cancer continues to be a significant source of both illness and death on a global scale, traditional medicinal plants continue to serve as a fundamental resource of natural bioactive compounds as an alternative source of remedies. Although there have been numerous studies on the therapeutic role of Phoenix dactylifera, the study of the role of peptides has not been thoroughly investigated. This study aimed to investigate the anticancer activity of lectin peptides from P. dactylifera using in silico and in vivo analysis. Methods: Different computational tools were used to extract and predict anticancer peptides from the true lectins of P. dactylifera. Nine peptides that are bioactive substances have been investigated for their anticancer activity against MCF-7 and T47D (two forms of breast cancer). To counteract the unfavorable effects of mitotane, the most potent peptides (U3 and U7) were combined with it and assessed for anticancer activity against MCF-7 and HepG2. Results: In silico analysis revealed that nine peptides were predicted with anticancer activity. In cell lines, the lowest IC₅₀ values were measured in U3 and U7 against MCF-7 and T47D cells. U3 or U7 in combination with mitotane demonstrated the lowest IC₅₀ against MCF-7 and HepG2. The maximum level of cell proliferation inhibition was 22% when U3 (500 µg/mL) and 25 µg/mL mitotane were combined, compared to 41% when 25 µg/mL mitotane was used alone. When mitotane and U3 or U7 were combined, it was shown that these bioactive substances worked synergistically with mitotane to lessen its negative effects. The combination of peptides and mitotane could be regarded as an efficient chemotherapeutic medication having these bioactive properties for treating a variety of tumors while enhancing the reduction of side effects.

Keywords: HepG2; MCF-7 breast cancer cells; date palm; in silico analysis; liver cancer.

FIGURE 1

Percentage of cell viability of MCF-7 and T47D treated with peptide U1, U2, U3, U4 (A) and U5, U6, U7, U8, U9 (B). Cells treated with peptides were incubated for 48 h and cell viability was evaluated using an MTT assay. Cell viabiltity percentage were obtained by the logarithm of the concentration of each peptide. The IC₅₀ value was determined using GraphPad. Experiments were performed three times independently (n = 3).

FIGURE 2

Percentage of viability of MCF-7 and HepG2 treated with U3 and U7. Cells treated with U3 and U7 peptides were incubated for 48 h and cell viability was evaluated using an MTT assay. Cell viabiltity percentage were obtained by the logarithm of the concentration of each peptide. The IC₅₀ value was determined using GraphPad. Experiments were performed three times independently (n = 3).

FIGURE 3

Percentage of viability of MCF-7 treated with mitotane combined with U3 and U7 The serial dilution of concentration of mitotane (20–600 µM) and various concentrations of U3 or U7 (40–1500 µM). Serial dilution of mitotane concentration with a fixed concentration of U3 or U7 (500 µg/mL). Cells treated with mitoten, peptides and their combinations were incubated for 48 h and cell viability was evaluated using an MTT assay. Cell viabiltity percentage were obtained by the logarithm of the concentration of each peptide. The IC₅₀ value was determined using GraphPad. Experiments were performed three times independently (n = 3).

FIGURE 4

Percentage of viability of HepG2 treated with mitotane combined with U3 and U7. The serial dilution of concentration of mitotane (20–600 µM) and various concentrations of U3 or U7 (40–1500 µM). Serial dilution of mitotane concentration with a fixed concentration of U3 or U7 (500 µg/mL). Cells treated with mitoten, peptides and their combinations were incubated for 48 h and cell viability was evaluated using an MTT assay. Cell viabiltity percentage were obtained by the logarithm of the concentration of each peptide. The IC₅₀ value was determined using GraphPad. Experiments were performed three times independently (n = 3).

FIGURE 5

% of viability of MCF-7 and HepG2 treated with combined mitotane at conc 25 µg/mL. The data obtained from Figures 3, 4.