Artesunate promotes Th1 differentiation from CD4+ T cells to enhance cell apoptosis in ovarian cancer via miR-142

Abstract

The aim of this study was to evaluate the influence of artesunate on Th1 differentiation and its anti-tumor effect on ovarian cancer. A Murine ovarian cancer model was established by ID8 cells transplantation. The expression of miR-142 and Sirt1 proteins in peripheral CD4 + T cells were quantified with qRT-PCR and western blot, respectively. Peripheral CD4 + T cells were induced for Th1 differentiation. The percentages of apoptosis of Th1/CD4 + T cells and ovarian cancer cells were analyzed by flow cytometry. The IFN-γ level was examined through enzyme-linked immunosorbent assay. Artesunate promoted miR-142 expression in peripheral CD4 + T cells and Th1 differentiation from CD4 + T cells. Artesunate promoted cell apoptosis of ovarian cancer cells by inducing Th1 differentiation. By up-regulating miR-142, artesunate suppressed Sirt1 level and promoted Th1 differentiation. Artesunate enhanced the pro-apoptotic effects of Th1 cells on ovarian cancer via the miR-142/Sirt1 pathway. Artesunate promoted Th1 differentiation from CD4 + T cells by down-regulating Sirt1 through miR-142, thereby enhancing cell apoptosis in ovarian cancer.

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

“…As an analog of ART, artesunate exerts better water solubility and higher oral bioavailability, due to its special structure with an additional hemisuccinate group that makes it a better candidate for cancer treatment [668]. The anti-cancer effects of artesunate have been demonstrated in bladder, breast, cervical, colorectal, esophageal, gastric, ovarian and prostate cancer, renal carcinoma, leukemia, melanoma and multiple myeloma [179,[669][670][671][672][673][674][675][676][677][678][679]. Its anti-cancer effects include induction of cell cycle arrest and apoptosis, inhibition of cell proliferation and growth, metastasis and angiogenesis [670,678,680].…”

“…Immunomodulation also plays a vital role in artesunate-mediated anti-cancer effects [671,674,691,692]. Artesunate induces Th1 differentiation into CD4 + T cells to mediate apoptosis in murine ovarian cancer ID8 cells [674].…”

“…Immunomodulation also plays a vital role in artesunate-mediated anti-cancer effects [671,674,691,692]. Artesunate induces Th1 differentiation into CD4 + T cells to mediate apoptosis in murine ovarian cancer ID8 cells [674]. It also exerts anti-tumor effects through suppressing NK killing activity and lymphocyte proliferation, which results in decreased TGF-β1 and IL-10 levels in colorectal cancer Colon-26 and RKO cells [691].…”

Artemisinins as Anticancer Drugs: Novel Therapeutic Approaches, Molecular Mechanisms, and Clinical Trials

“…As shown in Figure 3 , the mechanisms of action involve multiple cell signaling pathways. Besides, reports showed that ARTs regulated cancer cell metabolism including glucose metabolism and lipid metabolism, inhibited immunosuppression and the stemness of cancer stem cells in various cancer cell lines ( Chen X. et al, 2017 ; Cao et al, 2019 ; Chen X. et al, 2019 ; Chen S. et al, 2020 ; Gao et al, 2020 ). These new findings further highlight the multitarget bioactive properties and complexity of the ART-mediated anticancer effect.…”

“…In addition, the expression of miRNAs was affected by ARS treatment, leading to regulation of immunosuppression. In ovarian cancer, ARS up-regulated miR-142 that in turn suppressed Sirt1 level and promoted T helper 1 cell differentiation, thereby enhancing cell apoptosis ( Chen X. et al, 2019 ). In bladder cancer, ARS up-regulated miR-16 expression, which decreased cyclooxygenase 2 expression and prostaglandin production ( Jiang et al, 2018 ).…”