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Background/Aim: Cumulus cells (CCs) originate from the membrane granulosa cells and surround oocytes during follicle maturation. CCs produce high levels of hyaluronan that targets CD44, which is a major tumorigenic marker. This study aimed to investigate whether CCs have a role in cell therapy by targeting CD44 in pancreatic cancer cells. Materials and Methods: CCs were isolated from the oocytes and incubated in a hypoxic environment. BxPC-3 pancreatic cancer cells were treated with CC conditioned media for three days. Results: Conditioned media of CC cells incubated in hypoxic conditions caused a 25% reduction in the viability of BxPC-3 cells. Expression of anti-apoptotic genes was down-regulated, while that of pro-apoptotic genes was upregulated. An increased number of BxPC-3 cells exhibited increased levels of reactive oxygen species and arrested in the synthesis (S) phase of the cell cycle. Conclusion: CCs conditioned medium induced apoptosis of pancreatic cancer cells. Cumulus cells (CCs) are a specialized group of granulosa cells, which are in intimate contact with oocytes (1, 2) both in the ovarian follicle and after ovulation. CCs are removed in routine human intra-cytoplasmic sperm injection (ICSI) practices for better capturing of the polar body. CCs play an essential role in regulating oocyte maturation (3, 4); they surround the mature oocyte and give rise to a cumulus mass of several millimeters (5). Several studies on CCs have focused on their role in oocyte maturation and fertilization and on their use as novel non-invasive diagnostic biomarkers to determine oocyte quality (6). Many types of cancers are characterized by elevated levels of reactive oxygen species (ROS), which play an essential role in cell proliferation, differentiation, and cell survival (7). CCs have a protective effect against ROS, but only to a certain extent. The process of CC expansion requires the production of hyaluronic acid (8, 9), which is the primary CD44 binding molecule overexpressed in many solid tumors, such as pancreatic cancer (10). CD44 is a non-kinase transmembrane glycoprotein, which has been shown to be overexpressed in a variety of cells such as cancer stem cells and mutations in this gene are thought to play a role in tumorigenesis (11). Targeting this protein through CCs might have an anti-carcinogenic effect on pancreatic cancer cells. Materials and Methods Tissue collection and sample preparation. The tissue of origin of CCs was obtained from the IVF lab. Tissues were minced in phosphate buffered saline (PBS) by pipetting vigorously and transferred into T25 flasks coated with Type I Collagen (STEMCELL Technologies, Kent, WA, USA). CCs were cultured in RPMI-1640 (Life Technologies, Grand Island, NY, USA), supplemented with 10% FBS (Life Technologies) and 1% penicillin/streptomycin/amphotericin (PSA) Life Technologies), and incubated in hypoxic conditions (2% O 2). Floating tissues and cells flask were discarded and the medium was replaced with fresh medium and left in the incubator for three to four days. Co...