Cisplatin is a standard treatment for prostate cancer, which is the third leading cause of cancer-related deaths among men globally. However, patients who have undergone cisplatin can rxperience relapse. tRNA-derived fragments (tRFs) are small non-coding RNAs generated via tRNA cleavage; their physiological activities are linked to the development of human diseases. Specific tRFs, including tRF-315 derived from tRNA^Lys, are highly expressed in prostate cancer patients. However, whether tRF-315 regulates prostate cancer cell proliferation or apoptosis is unclear. Herein, we confirmed that tRF-315 expression was higher in prostate cancer cells (LNCaP, DU145, and PC3) than in normal prostate cells. tRF-315 prevented cisplatin-induced apoptosis and alleviated cisplatin-induced mitochondrial dysfunction in LNCaP and DU145 cells. Moreover, transfection of tRF-315 inhibitor increased the expression of apoptotic pathway-related proteins in LNCaP and DU145 cells. Furthermore, tRF-315 targeted the tumor suppressor gene GADD45A, thus regulating the cell cycle, which was altered by cisplatin in LNCaP and DU145 cells. Thus, tRF-315 protects prostate cancer cells from mitochondrion-dependent apoptosis induced by cisplatin treatment.

Colon cancer is one of the most frequently diagnosed cancer types. Some colon cancer cases resist standard anticancer drugs. Therefore, many studies have focused on developing therapeutic supplements using natural products with low side effects and broad physiological activity. Eupatilin is a flavonoid that is mainly extracted from artemisia and promotes apoptosis in numerous cancer types. However, since the current understanding of its physiological mechanisms on colon cancer cells is insufficient, we investigated how eupatilin affects the growth of two colon cancer cell lines, namely HCT116 and HT29. Our results showed that eupatilin inhibits cell viability and induces apoptosis accompanied by mitochondrial depolarization. It also induces oxidative stress in colon cancer cells and regulates the expression of proteins involved in the endoplasmic reticulum stress and autophagic process. Moreover, eupatilin may target the PI3K/AKT and mitogen-activated protein kinase (MAPK) signaling pathways in colon cancer cells. It also prevents colon cancer cell invasion. Furthermore, eupatilin has a synergistic effect with 5-fluorouracil (5-FU; a standard anticancer drug) on 5-FU-resistant HCT116 cells. These results suggest that eupatilin can be developed as an adjuvant to enhance traditional anticancer drugs in colon cancer.

Ovarian cancer has a high mortality rate and high resistance to chemotherapy. Thus, many studies are currently assessing the ability of natural products to induce ovarian cancer cell death. A coumarin derivative, 4-methylumbelliferone (4-MU), has been reported to have anti-cancer effects on various cancers, but its effects on ovarian cancer are not fully understood. In this study, we identified the intracellular mechanism underlying the effects of 4-MU on epithelial ovarian cancer cells. Decreased ovarian cancer cell proliferation and an accumulation of cells in the G2/M phase were observed following 4-MU treatment. Moreover, 4-MU interfered with calcium homeostasis; induced endoplasmic reticulum stress in both cell lines; inhibited AKT and S6 phosphorylation; and increased ERK1/2, P38, and JNK phosphorylation. Furthermore, 4-MU and pharmacological inhibitors showed synergic effects in suppressing cell proliferation. Collectively, our current data indicate that antitumor effects of 4-MU could be appropriate for use as a therapeutic agent against epithelial ovarian cancer cells.