Acute leukemia is characterized by rapid and unusual excess leukocyte proliferation. In this type of cancer, small molecular carriers like extracellular vesicles (EVs) can contribute to tumorigenesis since they can promote cancer cell growth and support the survival of cancer cells. These EVs are used in cell-cell communication and their ability to reprogram surrounding cells. Natural compounds can however, counteract these cellular mechanisms.
A compound found in black pepper called Piperine has anticancer activity towards many cancer cells. It also has antimicrobial and antioxidant effects. It has minimal effect on normal peripheral blood mononuclear cells (PMBCs) via the apoptosis signaling pathway. Researchers at Mahidol University in Thailand investigated the involvement of EVs in piperine-induced apoptosis in acute leukemia. Leukemic cell lines NB4 (acute promyelocytic leukemia) and MOLT-4 (T-lymphocytic leukemia) were treated with different Piperine concentrations and cell viability, apoptosis and cell cycle distribution were reviewed using MTT assays and flow cytometry. They found Piperine can inhibit cell proliferation and induce apoptosis in both these models. Piperine inhibited cell proliferation in a dose- and time-dependent way with minimal effects on normal PMBCs.
Natural compounds could be used to prevent cancer, or could be used to reduce chemotherapy doses. They can also be combined with other chemical compounds.
Studies have revealed Piperine’s anticancer effect is due to mediating various signaling pathways like PI3K/Akt/mTOR and Wnt/β-catenin signaling pathways. Apoptosis-mediated cell death is a strategy for cancer cell elimination by targeting molecules in signaling pathways to trigger the caspase cascade.
Researchers used Piperine in combination with the chemotherapeutic agent Daunorubicin (TOKU-E) to review any synergistic effects. They found the viability of NB4 and MOLT-4 cells treated with Piperine+ Daunorubicin was significantly decreased compared to Piperine or Daunorubicin alone or to the control, thus this demonstrated a synergistic effect.
Authors used Penicillin-Streptomycin to control contamination during cell culture. In addition, Sodium Dodecyl Sulfate (SDS) was used in the MTT assay to stop the reaction and solubilize the formazan crystals in the assay.
This work highlights the potential of natural compounds like Piperine for anti-cancer properties and shows how it can be combined with other chemotherapeutic compounds for added efficacy.
Reference
Charoensedtasin K, Kheansaard W, Roytrakul S, Tanyong D (2025) Anticancer effect of piperine, a black pepper compound, regulating apoptosis mediated through extracellular vesicles and cathepsin D in acute leukemia. Sci Rep. 15(1):45058 PMID 414234833 Link.